Download shifa clinical research center

SHIFA CLINICAL
RESEARCH CENTER
Policies and Guidelines Manual
“Research is defined as any systematic investigation designed to develop or contribute to
generalizable knowledge”.
"Research is to see what everybody else has seen, and to think what nobody else has thought."
- Albert Szent-Gyorgyi
Shifa International Hospital
TABLE OF CONTENTS
___________________________________________
Research Policies
MISSION and VISION STATEMENT
5
I. RESEARCH AND RESEARCH COMPLIANCE
1.1 Purpose of Policy
1.2 Scope of Policy
1.3 Glossary
6
6
6-11
2. OFFICE SUPPORTING RESEARCH
12
2.1 RO working: proposals, routing, communication with PI’s
2.2 IRB working: review criteria, time frame
12-15
16-19
3. Academic Policies Pertaining Research
3.1 Ethical Principles
3.2 Health professional-Pharmaceutical relationship
3.3 Conflict of Interest
30-33
3.4 Authorship
20
20
29
4. Financial Aspects of Research proposal
4.1 Budget
4.2 Funding Policy
4.3 Receipt and Disbursement of research Funds
4.4 Cost Estimation
4.5 Research Fund Management
4.6 Agreements /Contracts/MOU’s
39
39
39
40
40-41
41
41
5. Non-Faculty Research Appointments
42
2|Page
34-39
___________________________________________
Research Policies
6. REGULATORY COMPLIANCE
43
6.1 Human subjects in research
6.2 Environment Health and Safety
6.3 Laboratory Animals in Research
6.4 Ministry of Health and Regulatory Authorities
6.5 Safety Events and Reporting
7. OTHERS
7.1 Informed Consent Form (ICF) and Guidelines
7.2 Checklist for Completion of Informed Consent Form (ICF)
7.3 Research involving pregnant women or fetuses
7.4 Research involving neonates
7.5 Research involving the placenta, the dead fetus or fetal material
7.6 Form-A: research application form
107
7.7 Form-B: modifications/amendments to research proposal
7.8 Form-C: budget form (estimates for support requested)
7.9 Form-D: potential hazards and toxicity
111
7.10
Regulatory compliance
8
GUIDELINES
9
REFERENCES
3|Page
43-48
49-57
58-92
93
93
94
94-95
96
97
98-99
99
100108
109
110112-113
114
___________________________________________
Research Policies
‫أﻓـﻼ ﺗـﺘـﻔـﻜـﺮون‬
MISSION STATEMENT
Facilitating an ethical, scientific and collaborative journey of reflection, inquiry, discovery and
innovation.
VISION STATEMENT
4|Page
___________________________________________
Research Policies
Leading national and global collaborative efforts in clinical research, aiming for creation of
beneficial knowledge ("Ilman Nafian" )translating into healing (Shifa) for humanity.
I.
1.1
RESEARCH AND RESEARCH COMPLIANCE
PURPOSE OF THE RESEARCH CENTER
To contribute to knowledge translation in health sciences through clinical outcomes based
research, capacity building and infrastructure development and to provide research opportunities
for health professionals at the clinician/faculty, postgraduate and undergraduate level at Shifa
International Hospital in liason with affliated institutions . The Research center will also review
proposals for submission to IRB or referred from IRB ; make recommendations for amendment
and/or approval.
1.2
SCOPE OF POLICY
This research governance policy applies to all individuals involved in the conduct of clinical
research taking place within or facilitated by SIH, SCM & SCN and administered hospitals and
clinics.
1.3
GLOSSARY
Research: Research may be defined as "a systematic investigation, including research
development, testing and evaluation, designed to develop or contribute to generalizable
knowledge”.
Researcher: The person conducting the study.
Principal Investigator: The person authorized to take overall responsibility for the research
being conducted.. If a team of researchers is conducting the research, the Principal Investigator is
the leader responsible for that team.
Co--Investigator: Any individual member of the research team designated and supervised by the
investigator to perform procedures and/or to make important decisions (e.g.,clinical research associates,
residents, research fellows). See also Investigator.
5|Page
___________________________________________
Research Policies
Human Subjects: A “human subject” is a living individual about whom an investigator
(whether professional or trainee) conducting research obtains (1) data through intervention,
experimentation or interaction with the individual, or (2) involves identifiable private
information.
6|Page
___________________________________________
Research Policies
Risk: Risk means that the probability and magnitude of harm or discomfort anticipated in the
research are not greater than those ordinarily encountered in daily life or during the performance
of routine physical or psychological examinations or tests
Benefit: A research benefit is considered to be something of health-related, psychosocial, or
other value to an individual, research subject, or something that will contribute to the acquisition
of generalizable knowledge.
Money or other compensation for participation in research is not considered to be a benefit, but
rather compensation for research-related inconveniences.
Protocol: A document that describes the objective(s), design, methodology, statistical
considerations, and organization of a study.
Institutional Review Board (IRB)/ Ethics committee (EC): An independent body constituted
of medical, scientific, and non-scientific members, whose responsibility is to ensure the
protection of the rights, safety and well-being of human subjects involved in a research
study/trial by, among other things, reviewing, approving, and providing continuing review of
research/trial protocol and amendments and of the methods and material to be used in obtaining
and documenting informed consent of the subjects.
Informed Consent: A process by which a subject voluntarily confirms his or her willingness to
participate in a particular study, after having been informed of all aspects of the study that are
relevant to the subject's decision to participate. Informed consent is documented by means of a
written, signed and dated informed consent form.
Impartial Witness: A person, who is independent of the study, who cannot be unfairly
influenced by people involved with the study, who attends the informed consent process if the
subject or the subject’s legally acceptable representative cannot read, and who reads the
informed consent form and any other written information supplied to the subject.
Legally Acceptable Representative: An individual or juridical or other body authorized under
applicable law to consent, on behalf of a prospective subject, to the subject's participation in the
clinical study.
Serious Adverse Event (SAE) or Serious Adverse Drug Reaction (Serious ADR)
Any untoward medical occurrence that at any dose:
Results in death
Is life-threatening
Requires inpatient hospitalization or prolongation of existing hospitalization, results in
persistent or significant disability/incapacity.
Is a congenital anomaly/birth defect.
7|Page
___________________________________________
Research Policies
Regulatory Authorities: Bodies having the power to regulate. In the ICH GCP (?) guideline the
expression Regulatory Authorities includes the authorities that review submitted clinical data and
those that conduct inspections. These bodies are sometimes referred to as competent authorities.
Multicentre Study: A clinical study conducted according to a single protocol but at more than
one site, and therefore, carried out by more than one investigator.
Vulnerable Subjects: Individuals whose willingness to volunteer in a clinical study may be
unduly influenced by the expectation, whether justified or not, of benefits associated with
participation, or of a retaliatory response from senior members of a hierarchy in case of refusal to
participate. Other vulnerable subjects include patients with incurable diseases, persons in nursing
homes, unemployed or impoverished persons, patients in emergency situations, ethnic minority
groups, homeless persons, nomads, refugees, minors, and those incapable of giving consent.
Well-being: The physical and mental integrity of the subjects participating in a clinical study.
Alternative hypothesis: The alternative hypothesis states that an association between predictor
and outcome variables is present. It represents the possibility that the experientially observed
effect is genuine. It cannot be tested directly. The classical approach is to calculate the
probability that the observed effect will occur if the null hypothesis (aka random chance) is true.
If this value (the “p-value”) is small, then the null hypothesis is rejected in favor of the
alternative hypothesis.
Categorical variables: phenomena that cannot be quantified, thereby measured by classifying
into categories. Example: blood type, gender.
Cluster sample: sampling technique where the entire population is divided into natural
groupings, or clusters, and a random sample of these clusters is selected.
Continuous variable: rich in information; have quantified intervals on an infinite scale of
values.
Confidence interval (CI): statistic calculated from the range of the lower confidence limit and
the upper confidence limit. A 95% CI indicates, that if the study were replicated several times,
there is a 95% chance that the same results would be obtained.
Correlation coefficient: measures strength and direction of the linear relationship between 2
variables.
Dependent variable: A dependent variable is what is measured as an endpoint in an experiment.
The dependent variable responds to or is affected by the independent variable. It is called
dependent because it "depends" on the independent variable.
Design: the way in which you conceptualize your research project.
8|Page
___________________________________________
Research Policies
Exclusion criteria: defines the subset of population not eligible for study participation; if too
excessive, then ability to generalize becomes compromised.
Hypothesis: version of research question that summarizes all of its elements: sample, design,
predictor variables, outcome variables. Hypothesis establishes basis for tests of statistical
significance.
Incidence: statistic obtained from a cohort study; proportion of variable over a period of time.
Inclusion criteria: define the main characteristics of the subject population.
Independent variable: An independent variable is the variable a researcher can choose,
control and/or manipulate. It is presumed to affect or determine a dependent variable. one
that comes before the outcome variable does not change. May be
a qualifier, or descriptor of study population, Also known as, predictor variable.
Intervention: special predictor variable that the investigator manipulates.
Measurement scales: describe phenomena that can be analyzed statistically; continuous or
ordered discrete and categorical variables considered with methods.
Methods: detailed tasks, steps, stages and procedures you will use to conduct the study.
Null hypothesis: states that there is no association between the predictor and the outcome
variable. It is the opposite of the alternative or research hypothesis. Ideally, you want the data to
prove the null hypothesis is false, which makes your (“research”) hypothesis true.
Odds ratio: estimate of strength of association between each predictor variable and presence or
absence of disease.
Ordered discrete: scale with a finite number of intervals.
Outcome variable: variable often being measured as endpoint, Also known as the dependent
Variable
Power analysis: procedures and formulas that allow the researcher to determine the likelihood
of achieving statistical significance with a particular sample size. Contains four variables in its
calculation:
1. level of significance set by the researcher (identified as alpha, typically alpha is given the
value of .05)
2. probability of obtaining a significant result (power desired computed as 1-beta, typically
beta is given the value of 0.8)
3. population effect size, or the hypothesized effect on the groups
4. sample size
Predictor variable: one that comes before the outcome variable. Does not change. May be a
9|Page
___________________________________________
Research Policies
qualifier, or descriptor of study population. Also known as, independent variable.
Prevalence: statistic obtained from a cross-sectional study; proportion of variable at one point in
time.
P-value: measures the strength of evidence in support of the null hypothesis. Since the null
hypothesis is the opposite of the study hypothesis, naturally you would want your data to support
your study hypothesis and not the null hypothesis. A p-value less than or equal to .01 is
generally considered statistically significant. A p-value less than or equal to .005 or less than or
equal to .001 is considered highly significant.
Research question: what outcomes the study addresses.
Sample size: number of subjects needed to observe the expected difference in outcome between
study groups with a reasonable degree of probability or power.
Significance: in regards to the study question - why is the question important, how will it
contribute to society, what benefit will it bring, any existing research around this topic that may
have left unanswered questions, or questions you wish to challenge.
In regards to statistics - a result is considered (statistically) significant if it is unlikely to have
occurred by chance. The significance level is usually represented by the Greek symbol α (alpha).
Simple random sample: give numbers to qualifying sample population, then randomly select
Participants
Stratified random sample: dividing the population into subgroups based on specific criteria,
Then randomly selecting from each group, or “strata”
Study sample: subset of target population available for study.
Target population: defined by clinical, demographic, geographic population; who the results
will be generalized to.
Type I error: incorrectly concluding that the null hypothesis is false, when it is actually true.
The probability of committing a Type I error is equivalent to alpha, the significance level given
to the study.
Type II error: occurs when the test fails to reject the null hypotheses as false when it is in fact
False. Probability of this type of error decreases as the amount of data collected increases. The
Probability of committing this type of error is equivalent to beta. The probability of not
Committing a Type II error is equivalent to power.
Validity: how well the measurement represents the phenomenon of interest.
10 | P a g e
___________________________________________
Research Policies
2. OFFICE SUPPORTING RESEARCH
2.1 RESEARCH OFFICE:
The administrative office of the Research Center is responsible for processing, reviewing,
implementation and monitoring of research at the institution.
Procedures/Guidelines
Submission of a Research Proposal
2.1.1 A scientific research proposal may describe any one of the following biomedical research
activities in humans:
Use Of Category I Drug: A Formulary drug for an unlabelled indication or in a
combination or dosage different from that recommended by the manufacturer.
Use Of Category II Drug: A non-Formulary drug in a Phase II/III trial.
Use of a device
A procedure
A clinical diagnostic problem
A physiological function or effect
The pathophysiology of a disease
A research project in any area of health care/ sciences
2.1.2
All protocols shall be written according to the research proposal format of the Research
Center.
2.1.3
The Principal Investigator(s) shall submit the completed protocol, through their
Department Chairman/Section Head, to the Research Office for Full Review, Expedited
Review or for Exempt Status.
2.1.4
The Research Office shall take the following actions:
Review the application for completeness and justified status review.
Send the application for review to the IRB, if complete.
take up to (maximum) 10 working days to review the application before sending it
to the IRB.
11 | P a g e
___________________________________________
Research Policies
The status review (Full, Expedite or Exempt) recommendations shall be sent by
the Research Office to the IRB.
Research application tracking system will be maintained by the RO for the
convenience of the applicants
2.1.5
The Institutional Review Board (IRB) approval will be documented before
commencement of any project.
IMPORTANT
Annual Reports on the progress of the study should be sent to the Research Office,
or more frequently if so specified by the RO. On completion/discontinuation of the
study, a Final Report should be sent to the Research Office which in turn will send
it to the IRB.
2.1.6
General Instructions for the Principal Investigator
The research proposal should be carefully planned before commencing writing.
Establishment of deadlines for the preparation of the proposal is important particularly in
collaborative investigations.
When writing a research proposal, the following format should be followed:
Use Basic English.
Avoid jargon and spell out acronyms when used initially.
Number ALL pages consecutively beginning with the first page of the proposal
and continuing to the last page.
Whenever possible, research proposals should be reviewed and proofread by an objective
colleague. More often than not, the colleague will draw the attention to some minor
points in the proposal that may have been overlooked.
12 | P a g e
___________________________________________
Research Policies
If an investigator wishes to participate in a multi-center study which has been initiated
and previously approved by an acknowledged academic, medical or research institution;
he/she must submit a copy of that proposal, together with the approval letter from the
associated institution. The Research Center shall review such proposals in an expedited
fashion.
If an outside company is sponsoring any research a copy of agreement between the drug
company and the hospital must be attached with the application.
Investigational drugs should be preferably kept in the hospital pharmacy. The hospital
pharmacy should inform the Research Office in writing once the drugs are received by
the hospital. The Pharmacy shall follow all procedures and protocols as outlined in the
protocol/sponsor’s guidelines for the appropriate storage of investigational product.
The principal investigator should submit the proposal with all relevant forms completed,
and a covering memo; through the concerned department chairman or head, to the
Research Office.
The proposal sent to the Research Office will be screened for compliance with
submission criteria.
Completed proposals will receive a reference number (e.g., 2011.01) used for tracking
and future correspondences.
The Research Office will arrange for the proposal to be forwarded to IRB for discussion.
The Principal Investigator will be contacted by the Research Office if any clarifications
or recommendations are required.
13 | P a g e
___________________________________________
Research Policies
The Principal Investigator will regularly update the Research Office, in writing, of the
progress of the research and any new information that comes up during the course of the
study (where applicable).
IRB will approve, disapprove or require clarification.
A deadline will be set by the Research Office for studies, which have exceeded the time
frame set by the Principal Investigator.
For studies that have attained IRB approval and have not been initiated within one year of
approval, will be considered null and void and a detailed report to be submitted by the
concerned Principal Investigator to the Research Office(PI or Principal Investigator
should be consistent throughout the document)
For Sponsored Research all possible hospital facilities may be utilized including but not
limited to Laboratory, Radiology and Pharmacy etc.
Research Center intranet website will be established for information, queries, forms,
application tracking and approval status etc.
CPSP Synopsis will be discussed within the individual departmental research forums and
reviewed by the Departmental Head or his designee besides the supervisor for that post
graduate trainee prior to IRB submission. Once approved by the IRB, synopsis can be
sent to CPSP.The Shifa Clinical research center shall help in capacity building with
scheduled workshops and seminars and for projects with IRB approval involving human
subject research at Shifa International Hospital
A reprint of any publication arising from the research project should be sent to the
Research Office.
14 | P a g e
___________________________________________
Research Policies
When a final report has been presented to the Research Office, the follow-up tracking
system will be closed.
A closed file of any research proposal should be kept in the Research Office for 2 years.
A separate space is to be allocated in the Hospital’s Medical Record Room /Clinical
research center for archiving study specific patients file for source document verification
and inspections/audits.
The Research Office through appointed Monitors shall perform Periodic Monitoring
Visits to the project site for audits/inspections as and when appropriate by giving prior
written notification to the concerned P.I to ensure protocol compliance.
All sponsored research will be brought to the Research Office which in turn will provide
full support to the P.I including but not limited to feasibility assessment, administrative
support, study staff, implementation processes, contract negotiations, IRB/EC
submission, Regulatory Authority submission/approval etc. to ensure timely initiation,
ethical conduct and successful completion of the projects.
2.2 INSTITUTIONAL REVIEW BOARD (IRB) & ETHICS COMMITTEE (EC)
FUNCTIONS
3. ACADEMIC POLICIES PERTAINING RESEARCH
3.1 ETHICAL PRINCIPLES
3.1.1 BELMONT REPORT
The National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research
issued "The Belmont Report: Ethical Principles and Guidelines for the Protection of Human Subjects of
Research." The report sets forth three principles underlying the ethical conduct of research: Respect for
persons, Beneficence, and Justice.
15 | P a g e
___________________________________________
Research Policies
Summary: On July 12, 1974, the National Research Act (Pub. L. 93-348) was signed into law,
there-by creating the National Commission for the Protection of Human Subjects of Biomedical
and Behavioral Research. One of the charges to the Commission was to identify the basic ethical
principles that should underlie the conduct of biomedical and behavioral research involving
human subjects and to develop guidelines which should be followed to assure that such research
is conducted in accordance with those principles. In carrying out the above, the Commission was
directed to consider: (i) the boundaries between biomedical and behavioral research and the
accepted and routine practice of medicine, (ii) the role of assessment of risk-benefit criteria in the
determination of the appropriateness of research involving human subjects, (iii) appropriate
guidelines for the selection of human subjects for participation in such research and (iv) the
nature and definition of informed consent in various research settings.
The Belmont Report attempts to summarize the basic ethical principles identified by the
Commission in the course of its deliberations. It is the outgrowth of an intensive four-day period
of discussions that were held in February 1976 at the Smithsonian Institution's Belmont
Conference Center supplemented by the monthly deliberations of the Commission that were held
over a period of nearly four years. It is a statement of basic ethical principles and guidelines that
should assist in resolving the ethical problems that surround the conduct of research with human
subjects. By publishing the Report in the Federal Register, and providing reprints upon request,
the Secretary intends that it may be made readily available to scientists, members of Institutional
Review Boards, and Federal employees. The two-volume Appendix, containing the lengthy
reports of experts and specialists who assisted the Commission in fulfilling this part of its charge,
is available as DHEW Publication No. (OS) 78-0013 and No. (OS) 78-0014, for sale by the
Superintendent of Documents, U.S. Government Printing Office, Washington, D.C. 20402.
3.1.2 NUREMBERG CODE
Trials of War Criminals Before the Nuremberg Military Tribunals Under Control Council. Law
No. 10, Vol 2, pp. 181-182. Washington, D.C.: U.S. Government Printing Office, 1949.
Developed in response to the Nuremberg Trials of Nazi doctors who performed unethical
experimentation during World War II, the Code was the first major international document to
provide guidelines on research ethics. It made voluntary consent a requirement in clinical
research studies, emphasizing that consent can be voluntary only if participants are able to
consent; they are free from coercion (i.e., outside pressure); and they comprehend the risks and
benefits involved.
1. The voluntary consent of the human subject is absolutely essential. This means that the
person involved should have legal capacity to give consent; should be so situated as to be
able to exercise free power of choice, without the intervention of any element of force,
fraud, deceit, duress, over-reaching, or other ulterior form of constraint or coercion; and
should have sufficient knowledge and comprehension of the elements of the subject matter
involved as to enable him to make an understanding and enlightened decision. This latter
element requires that before the acceptance of an affirmative decision by the experimental
subject there should be made known to him the nature, duration, and purpose of the
experiment; the method and means by which it is to be conducted; all inconveniences and
16 | P a g e
___________________________________________
Research Policies
hazards reasonable to be expected; and the effects upon his health or person which may
possibly come from his participation in the experiment.
The duty and responsibility for ascertaining the quality of the consent rests upon each
individual who initiates, directs or engages in the experiment. It is a personal duty and
responsibility which may not be delegated to another with impunity.
2. The experiment should be such as to yield fruitful results for the good of society,
unprocurable by other methods or means of study, and not random and unnecessary in
nature.
3. The experiment should be so designed and based on the results of animal experimentation
and knowledge of the natural history of the disease or other problem under study that the
anticipated results will justify the performance of the experiment.
4. The experiment should be so conducted as to avoid all unnecessary physical and mental
suffering and injury.
5. No experiment should be conducted where there is an a priori reason to believe that death or
disabling injury will occur; except, perhaps, in those experiments where the experimental
physicians also serve as subjects.
6. The degree of risk to be taken should never exceed that determined by the humanitarian
importance of the problem to be solved by the experiment.
7. Proper preparations should be made and adequate facilities provided to protect the
experimental subject against even remote possibilities of injury, disability, or death.
8. The experiment should be conducted only by scientifically qualified persons. The highest
degree of skill and care should be required through all stages of the experiment of those who
conduct or engage in the experiment.
9. During the course of the experiment the human subject should be at liberty to bring the
experiment to an end if he has reached the physical or mental state where continuation of the
experiment seems to him to be impossible.
10. During the course of the experiment the scientist in charge must be prepared to terminate the
experiment at any stage, if he has probable cause to believe, in the exercise of the good
faith, superior skill and careful judgment required of him that a continuation of the
experiment is likely to result in injury, disability, or death to the experimental subject.
3.1.2 WORLD MEDICAL ASSOCIATION DECLARATION OF HELSINKI
Introduction
17 | P a g e
___________________________________________
Research Policies
1. The World Medical Association has developed the Declaration of Helsinki as a statement
of ethical principles to provide guidance to physicians and other participants in medical
research involving human subjects. Medical research involving human subjects includes
research on identifiable human material or identifiable data.
2. It is the duty of the physician to promote and safeguard the health of the people. The
physician's knowledge and conscience are dedicated to the fulfillment of this duty.
3. The Declaration of Geneva of the World Medical Association binds the physician with the
words, "The health of my patient will be my first consideration," and the International
Code of Medical Ethics declares that, "A physician shall act only in the patient's interest
when providing medical care which might have the effect of weakening the physical and
mental condition of the patient."
4. Medical progress is based on research which ultimately must rest in part on
experimentation involving human subjects.
5. In medical research on human subjects, considerations related to the well-being of the
human subject should take precedence over the interests of science and society.
6. The primary purpose of medical research involving human subjects is to improve
prophylactic, diagnostic and therapeutic procedures and the understanding of the etiology
and pathogenesis of disease. Even the best proven prophylactic, diagnostic, and therapeutic
methods must continuously be challenged through research for their effectiveness,
efficiency, accessibility and quality.
7. In current medical practice and in medical research, most prophylactic, diagnostic and
therapeutic procedures involve risks and burdens.
8. Medical research is subject to ethical standards that promote respect for all human beings
and protect their health and rights. Some research populations are vulnerable and need
special protection. The particular needs of the economically and medically disadvantaged
must be recognized. Special attention is also required for those who cannot give or refuse
consent for themselves, for those who may be subject to giving consent under duress, for
those who will not benefit personally from the research and for those for whom the
research is combined with care.
9. Research Investigators should be aware of the ethical, legal and regulatory requirements for
research on human subjects in their own countries as well as applicable international
requirements. No national ethical, legal or regulatory requirement should be allowed to
reduce or eliminate any of the protections for human subjects set forth in this Declaration.
Basic Principles For All Medical Research
10. It is the duty of the physician in medical research to protect the life, health, privacy, and
dignity of the human subject.
11. Medical research involving human subjects must conform to generally accepted scientific
principles, be based on a thorough knowledge of the scientific literature, other relevant
sources of information, and on adequate laboratory and, where appropriate, animal
experimentation.
12. Appropriate caution must be exercised in the conduct of research which may affect the
environment, and the welfare of animals used for research must be respected.
13. The design and performance of each experimental procedure involving human subjects
should be clearly formulated in an experimental protocol. This protocol should be
18 | P a g e
___________________________________________
Research Policies
submitted for consideration, comment, guidance, and where appropriate, approval to a
specially appointed ethical review committee, which must be independent of the
investigator, the sponsor or any other kind of undue influence. This independent committee
should be in conformity with the laws and regulations of the country in which the research
experiment is performed. The committee has the right to monitor ongoing trials. The
researcher has the obligation to provide monitoring information to the committee,
especially any serious adverse events. The researcher should also submit to the committee,
for review, information regarding funding, sponsors, institutional affiliations, other
potential conflicts of interest and incentives for subjects.
14. The research protocol should always contain a statement of the ethical considerations
involved and should indicate that there is compliance with the principles enunciated in this
Declaration.
15. Medical research involving human subjects should be conducted only by scientifically
qualified persons and under the supervision of a clinically competent medical person. The
responsibility for the human subject must always rest with a medically qualified person and
never rest on the subject of the research, even though the subject has given consent.
16. Every medical research project involving human subjects should be preceded by careful
assessment of predictable risks and burdens in comparison with foreseeable benefits to the
subject or to others. This does not preclude the participation of healthy volunteers in
medical research. The design of all studies should be publicly available.
17. Physicians should abstain from engaging in research projects involving human subjects
unless they are confident that the risks involved have been adequately assessed and can be
satisfactorily managed. Physicians should cease any investigation if the risks are found to
outweigh the potential benefits or if there is conclusive proof of positive and beneficial
results.
18. Medical research involving human subjects should only be conducted if the importance of
the objective outweighs the inherent risks and burdens to the subject. This is especially
important when the human subjects are healthy volunteers.
19. Medical research is only justified if there is a reasonable likelihood that the populations in
which the research is carried out stand to benefit from the results of the research.
20. The subjects must be volunteers and informed participants in the research project.
21. The right of research subjects to safeguard their integrity must always be respected. Every
precaution should be taken to respect the privacy of the subject, the confidentiality of the
patient's information and to minimize the impact of the study on the subject's physical and
mental integrity and on the personality of the subject.
22. In any research on human beings, each potential subject must be adequately informed of
the aims, methods, sources of funding, any possible conflicts of interest, institutional
affiliations of the researcher, the anticipated benefits and potential risks of the study and the
discomfort it may entail. The subject should be informed of the right to abstain from
participation in the study or to withdraw consent to participate at any time without reprisal.
After ensuring that the subject has understood the information, the physician should then
obtain the subject's freely-given informed consent, preferably in writing. If the consent
cannot be obtained in writing, the non-written consent must be formally documented and
witnessed.
23. When obtaining informed consent for the research project the physician should be
particularly cautious if the subject is in a dependent relationship with the physician or may
19 | P a g e
___________________________________________
Research Policies
consent under duress. In that case the informed consent should be obtained by a wellinformed physician who is not engaged in the investigation and who is completely
independent of this relationship.
24. For a research subject who is legally incompetent, physically or mentally incapable of
giving consent or is a legally incompetent minor, the investigator must obtain informed
consent from the legally authorized representative in accordance with applicable law.
These groups should not be included in research unless the research is necessary to
promote the health of the population represented and this research cannot instead be
performed on legally competent persons.
25. When a subject deemed legally incompetent, such as a minor child, is able to give assent to
decisions about participation in research, the investigator must obtain that assent in addition
to the consent of the legally authorized representative.
26. Research on individuals from whom it is not possible to obtain consent, including proxy or
advance consent, should be done only if the physical/mental condition that prevents
obtaining informed consent is a necessary characteristic of the research population. The
specific reasons for involving research subjects with a condition that renders them unable
to give informed consent should be stated in the experimental protocol for consideration
and approval of the review committee.
The protocol should state that consent to remain in the research should be obtained as soon
as possible from the individual or a legally authorized surrogate.
27. Both authors and publishers have ethical obligations. In publication of the results of
research, the investigators are obliged to preserve the accuracy of the results. Negative as
well as positive results should be published or otherwise publicly available. Sources of
funding, institutional affiliations and any possible conflicts of interest should be declared in
the publication. Reports of experimentation not in accordance with the principles laid down
in this Declaration should not be accepted for publication.
Additional Principles For Medical Research Combined With Medical Care
28. The physician may combine medical research with medical care, only to the extent that the
research is justified by its potential prophylactic, diagnostic or therapeutic value. When
medical research is combined with medical care, additional standards apply to protect the
patients who are research subjects.
29. The benefits, risks, burdens and effectiveness of a new method should be tested against
those of the best current prophylactic, diagnostic, and therapeutic methods. This does not
exclude the use of placebo, or no treatment, in studies where no proven prophylactic,
diagnostic or therapeutic method exists.1
30. At the conclusion of the study, every patient entered into the study should be assured of
access to the best proven prophylactic, diagnostic and therapeutic methods identified by the
study.2
31. The physician should fully inform the patient which aspects of the care are related to the
research. The refusal of a patient to participate in a study must never interfere with the
patient-physician relationship.
20 | P a g e
___________________________________________
Research Policies
32. In the treatment of a patient, where proven prophylactic, diagnostic and therapeutic
methods do not exist or have been ineffective, the physician, with informed consent from
the patient, must be free to use unproven or new prophylactic, diagnostic and therapeutic
measures, if in the physician's judgment it offers hope of saving life, re-establishing health
or alleviating suffering. Where possible, these measures should be made the object of
research, designed to evaluate their safety and efficacy. In all cases, new information
should be recorded and, where appropriate, published. The other relevant guidelines of this
Declaration should be followed.
INTERNATIONAL CONFERENCE on HARMONIZATION / GOOD CLINICAL
PRACTICES (ICH/GCP) GUIDELINES FOR CONDUCTION OF CLINICAL
RESEARCH
Clinical Research should be conducted in accordance with the ethical principles that have
their origin in the Declaration of Helsinki, and that are consistent with GCP and the
applicable regulatory requirement(s).
Before a research is initiated, foreseeable risks and inconveniences should be weighed
against the anticipated benefit for the individual study subject and society.
Research should be initiated and continued only if the anticipated benefits justify the risks.
The rights, safety, and well-being of the study subjects are the most important
considerations and should prevail over interests of science and society.
The available nonclinical and clinical information on an investigational product should be
adequate to support the proposed clinical research (drug studies).
Clinical research project should be scientifically sound, and described in a clear, detailed
protocol.
A research project should be conducted in compliance with the protocol that has received
prior institutional review board (IRB)/independent ethics committee (IEC)
approval/favorable opinion.
The medical care given to, and medical decisions made on behalf of, subjects should always
be the responsibility of a qualified physician or, when appropriate, of a qualified dentist.
Each individual involved in conducting a research project should be qualified by education,
training and experience to perform his or her respective task(s).
Freely given informed consent should be obtained from every subject prior to clinical
research participation.
21 | P a g e
___________________________________________
Research Policies
All clinical research project information should be recorded, handled, and stored in a way
that allows its accurate reporting, interpretation and verification.
The confidentiality of records that could identify subjects should be protected, respecting
the privacy and confidentiality rules in accordance with the applicable regulatory
requirement(s).
Any Investigational product/s should be used in accordance with the approved protocol.
INVESTIGATORS RESPONSIBILITY FOR PROTECTING HUMAN SUBJECTS
Who are Investigators?
The term “Investigator” to refer to an individual performing various tasks related to
the conduct of human subjects research activities, such as obtaining informed consent
from subjects, interacting with subjects, and communicating with the IRB.
Investigators can include physicians, scientists, nurses, administrative staff, teachers,
and students, among others.
Some research studies are conducted by more than one investigator, and usually
one Investigator is designated the “principal investigator” with overall responsibilities
for the study.
What are Investigators responsible for?
Protecting the rights and welfare of the human subjects who participate in their
research.
They must also understand the ethical standards and regulatory requirements governing
their research activities
To conduct research on the agreed protocol and in accordance with the legal requirement
and guidance
22 | P a g e
___________________________________________
Research Policies
Obtaining IRB approval before beginning any human subject’s research.
Obtaining and documenting informed consent of subjects or subjects’ legally authorized
representatives prior to the subjects’ participation in the research.
Obtaining prior approval from the IRB for any modifications of the previously approved
research
Ensuring that progress reports and requests for continuing review and approval are
submitted to the IRB.
Providing to the IRB and Research center prompt reports of any unanticipated
problems involving risks to subjects or others
Providing to the IRB and Research center prompt reports of serious or continuing
noncompliance with the regulations or the requirements or determinations of the IRB.
To comply with internal and external audit requirements.
Keeping certain required documents for at least three years after completion of study.
3.2 HEALTH PROFESSIONAL-PHARMACEUTICAL RELATIONSHIP
Health professionals at SIH and STMU affiliated facilities who participate in industry
associated research will do so ONLY if that research meets accepted ethical, regulatory,
and scientific standards.
Health professionals at Shifa International Hospitals Limited will not be involved in
research in which the sponsor imposes any obstacle to publication of the study results.
Research whose primary purpose is promotion of a drug product or device is not legitimate
and does not hold patient welfare in the highest regard. As an example, the Health
professionals at SIH and STMU affiliates will not participate in studies for which the
primary purpose is to familiarize prescribers with specific drug products (i.e., marketing or
"seeding" studies).
Payments to patients, subjects, or health professionals participating in studies should be
reasonable and represent appropriate reimbursement for time and expenses.
Disproportionate fees for collection of patient data in a research study should lead one to
23 | P a g e
___________________________________________
Research Policies
evaluate closely the purpose of the study, as excessive compensation for conducting a study
constitutes a gift
If allowed by the funding agency, money that remains after all study expenses (such as
investigator and coordinator salaries and overhead) have been paid should be used to
support research training programs, enhance the educational or research mission of the
institution, or improve patient care directly.
Reimbursement of expenses for attending clinical investigators' meetings should avoid
unnecessary extravagance and cover the expenses of the investigators for the time of the
meeting only.
3.3 CONFLICT OF INTEREST
Why Should You Care About Conflicts of Interest
Conflicts of interest are intrinsic to a researcher's enterprise. Not only can a conflict harm
particular study participants but, on a larger scale, a conflict of interest can damage an entire
research enterprise by reducing the trust and confidence that people generally have in research.
Objectivity is fundamental to this trust
Definition of a Conflict of Interest
A conflict of interest involves the abuse -- actual, apparent, or potential -- of the trust that people
have in professionals. The simplest working definition states: “A conflict of interest is a situation
in which financial or other personal considerations have the potential to compromise or bias
professional judgment and objectivity”.
An apparent conflict of interest is one in which a reasonable person would think that the
professionals judgment is likely to be compromised. A potential conflict of interest involves a
situation that may develop into an actual conflict of interest. It is important to note that a conflict
of interest exists whether or not decisions are affected by a personal interest; a conflict of interest
implies only the potential for bias, not a likelihood. It is also important to note that a conflict of
interest is not considered misconduct in research, since the definition for misconduct is currently
limited to fabrication, falsification, and plagiarism.
There are many varieties of conflicts of interest, and they appear in different settings and across
all disciplines. While conflicts of interest apply to a "wide range of behaviors and
circumstances," they all involve the use of a person's authority for personal and/or financial gain.
Conflicts of interest may involve individuals as well as institutions. Furthermore, individuals, in
24 | P a g e
___________________________________________
Research Policies
certain circumstances, may have conflicts occurring on both an individual and an institutional
level, as may be seen among members of an Institutional Review Board (IRB).
Conflicts of interest are broadly divided into two categories: intangible, i.e., those involving
academic activities and scholarship; and tangible, i.e., those involving financial relationships.
Conflicts of Interest at the Individual Level
Objectivity is the sine qua non of scientific discovery. But bias in judgment is virtually
impossible to eliminate. There are often subtle, and not so subtle, pressures that can influence
how we perceive and how we act. All research professionals understand the pressures to publish,
to get funding, appointments, promotions, and to earn respect from peers.
In an effort to succeed, there are myriad areas where bias can influence judgment and diminish
objectivity. A desire to validate a pet theory, overconfidence about a particular concept,
overreliance on a belief held by a special group, ruling out data that don't support a hypothesis,
and internal or external pressures to get a specific result are all influences that may lead to
distortions in objectivity. Any of these biases or pressures may lead to what sociologists call
selective inattendance. Your mind-set may cause you to overlook important data or to
misperceive critical observations.
Bias can be too subtle to recognize and too difficult to control. It can creep into how research
questions are selected and framed, the choice of research design, the selection of research
participants, and how the data are collected, analyzed, interpreted, and ultimately published.
Whether you describe the glass as half empty or half full is influenced by what you want your
results to look like. Bias can even influence the sharing of the results of the study.
Academic Conflicts of Interest or Intellectual Bias
Academic scientists have special responsibilities to disseminate knowledge, to maintain
academic standards, to critique the current state of knowledge, to synthesize existing knowledge,
and to apply knowledge to solve basic and applied problems. The peer-review system is the
benchmark of the scientific process. An academic conflict of interest could occur if an
individual interferes with the peer-review process for some type of intangible personal gain. For
example, bias can cause a reviewer to respond positively to a manuscript because it presents
results favoring a method or production in which the reviewer has a personal interest or a
reviewer may act to delay the publication of a competitor's manuscript in order to strengthen his
or her own chances for publication or funding.
These are intangible interests, and they are indigenous to every researcher. Indeed, the drive for
recognition can be overwhelming, particularly when a future position or livelihood depends on
these public achievements.
Other Types of Conflicts of Interest
25 | P a g e
___________________________________________
Research Policies
In addition to academic conflicts of interest, there are other intangible conflicts that can
compromise objectivity. For example, conflicts of commitment, which may also be called
conflicts of effort or conflicts of obligation, occur when the extent of time spent on a secondary
activity competes with the time expected to be spent on teaching, research, or service by the
primary employer.
A conflict of conscience occurs when personal beliefs influence objectivity in research. For
example, a scientist may have a particular view on abortion that influences his or her view of the
scientific merit of a study that uses human embryonic stem cells.
Clinical Research
Clinical researchers subscribe to three basic elements: scientific integrity, patient safety, and
investigator objectivity. Yet these researchers are likely to experience conflicts of interest by
virtue of their altruistic dedication to the pursuit of knowledge while striving to maintain the
welfare of the human volunteers participating in their investigations. Bias and decreased
objectivity are of particular concern in the clinical-research setting, where the rewards and risks
are both potentially great. Here, bias in judgment might creep in not only to influence the
questions pursued and the choice of research design but also to affect the selection and retention
of research participants, the reporting and attribution of adverse events, and the collection,
statistical analysis, interpretation, and reporting of the data.
In assessing conflicts of interest, we need to consider the likelihood of bias as well as the
consequences of the conflict of interest, because at times the consequences can be lethal.
Safeguards
The scientific method includes a series of steps to ensure that the results of any study are
unprejudiced and repeatable. These steps include: identifying a problem through observation,
formulating a hypothesis, testing the hypothesis through data collection and analysis, and
deriving a conclusion that either confirms or fails to confirm the hypothesis.
Fortunately, there are safeguards that can be put into place to help reduce bias and improve
objectivity. Conscientious application of the scientific method is one such safeguard. For clinical
trials, randomized controlled trial designs ,a Data and Safety Monitoring Board (DSMB) may be
required. Vigilance is always necessary.
The Commercialism of Clinical Research
The research community has long recognized academic conflicts of interest. Lately, however,
there has been a sea change within the research enterprise, whereby the accelerating
commercialization of biomedical research is of mounting concern. A few statistics are telling:
research-and-development investments by pharmaceutical companies increased from $1.3 billion
in 1977 to $32 billion in 2002, a 24-fold increase in just 25 years, and PhRMA companies alone
spent more on pharmaceutical R. & D. than the total 2002 NIH (USA) operating budget of $24
billion.
26 | P a g e
___________________________________________
Research Policies
Clearly, commercialism is driving the scientific establishment, and this, indeed, can be
beneficial. Yet the intertwining of academic research and commercial interests can lead to
financial conflicts of interest. A financial conflict of interest involves some type of financial
payment, such as a consulting fee, equity in a company, or other monetary reward, which
influences an individual to prefer one outcome to another. Any of these can be problematic if
they are related to the product under study or the sponsor of the research.
Financial conflicts of interest are considered tangible conflicts, because they can be seen and
measured. While they appear easier to deal with than intangible conflicts of interest, they may
not be. Financial arrangements with sponsors are affecting many areas of scientific life. A
growing literature is documenting, with disturbing accounts, how the new entrepreneurial
environment is altering the publication practices and prescribing patterns of investigators and
clinicians.
Intangible conflicts of interest, as previously described, are problematic, but they are widely
recognized and shared. What has captured the attention of the scientific community and the
public are those conflicts caused by money and financial relationships, the tangible conflicts of
interest. Many fear that the cost of these relationships could be the integrity of science itself.
Note: To resolve any conflict of interest including but not limited to Scientific Misconduct,
Plagiarism, Fraud, Authorship issues, Data Ownership, Misconduct, Redundant Publications or
any other dispute, IRB/EC will meet to resolve any outstanding issues.
3.4 AUTHORSHIP
Introduction
The goal of research and scholarly publication is the timely dissemination of information to
scholars, students, and the general public in order to engage them in the challenge of discovery,
enhancement of knowledge and the improvement of life. In turn, authorship to a scholarly and
research publication has come to serve the academic profession as a highly dependable
recognition of merit.
Academic success and promotions are judged by the number of quality publications in peerreviewed journals. These are considered to be the main determinants of academic grading in
higher education. Therefore, the pressure to publish is such that researchers are often tempted to
be co-authors in a paper without having made substantial intellectual and scientific contribution.
This issue is not unique to Pakistan. Groups of researchers and editors all over the world have
been suggesting mechanisms and defining criteria to resolve issues related to authorship. The
International Committee of Medical Journals Editors, (ICMJE, also known as the Vancouver
group) drew up guidelines based on the principal that each author should be able to define-thework and to defend-the-work publicly. These guidelines may be summarized as:
27 | P a g e
___________________________________________
Research Policies
Authorship should be based only on a substantial contribution to:
Conception and design or analysis and interpretation of data.
Drafting the article or revising it critically for important intellectual content and
Final approval of the version to be published.
All the above criteria must be met. Participation solely in the collection of data, supervision of
study activity, or acquisition of funding does not constitute authorship.
ICMJE criteria (2000) require that ‘each author should have participated sufficiently in the work
to take public responsibility for appropriate portions of the content. One or more authors should
take responsibility for the integrity of the work as a whole, from inception to published article.
Fields like Nursing Research and Education have adopted very similar guidelines for authorship.
The American Psychological Association Manual (APA Manual) further clarifies that the order
of assigned authorship should reflect the relative contributions to the work and not the relative
status of the individuals.
Objectives and Principles:
The institution’s Authorship Guidelines seek to establish a clear and sound framework for the
encouragement of invention, innovation, creative work and technological development. It
provides a framework for managing the institution’s authorship policy objectives, which are:
I.
II.
Establish and enhance the climate for innovation and invention;
Foster a healthy environment for education, research and development;
III.
Avoid disputes over attribution of academic credit;
IV.
Recognize respective rights of faculty, students and research staff to
authorship of publishable material towards which they have made significant
contributions.
General principles regarding authorship
28 | P a g e
4.3.1
Authorship credit must be assigned only to those whose
contributions are substantial.
4.3.2
Each author should have participated in formulating the research
problem, designing and implementing the study, interpreting the
results, writing and reviewing the research paper, and should be
prepared to defend the publication against criticism. All authors are
publicly accountable for the content and conclusions of the paper.
___________________________________________
Research Policies
4.3.3
The order of authorship should reflect the relative contributions of
various participants in the project. The intellectual and substantive
contributions of research team members to the project should be
stated on all papers and presentations resulting from the project.
An editor may request written documentation of each author’s
contribution.
4.3.4
If participants of a research project have contributed equally, and
no one person can be identified as having a more significant role
than others, then the group may consider representing themselves
by a corporate (collective) title (if acceptable to the relevant
journal). The article should then carry a footnote containing the
names and contributions of individuals represented by the
collective title.
4.3.5
In the case of equal contributions to a publication, authorship may
also be assigned by listing names alphabetically, with a qualifying
statement that all contributions are equal.
4.3.6
In a project that may lead to multiple publications, each
investigator may take turns to be the first author on at least
one publication, provided his/her contribution to all
publications is equal. This may be determined based on the
level of individual involvement and interests in a particular
aspect of the study. Please refer to section 7.0 for further
guidance.
4.3.7
Individuals who make substantial contributions to a paper but are
not project team members may be recognized as an author.
4.3.8
Gift [1] and ghost [2] authorship are strictly not acceptable.
4.3.9
Contributions of those who are not co-authors (such as those
providing technical assistance or those involved in data
collection) must be acknowledged.
4.3.10 The investigative team and funding source must be acknowledged
on all papers and presentations resulting from the project.
4.3.11 Titles for papers and presentations must be discussed by the
research team to avoid overlaps, omissions and controversy.
29 | P a g e
___________________________________________
Research Policies
4.3.12 Before being submitted, the paper should be reviewed by the
Principal Investigator (PI) if this person is not an author on the
paper.
4.3.13 Authors should notify the editor if they have published or
submitted elsewhere for publication the same or a substantially
similar manuscript if a transfer of copyright is involved.
4.3.14 All authors should sign the letter of transmittal and copyright
release form. (It is not sufficient for one author to do so on behalf
of the others).
Gift authorship: is defined as co-authorship awarded to a person who has not contributed
significantly to the research project. Junior researchers often feel pressured to accept or assign
honorary authorship to their supervisors or senior co-workers who have substantial powers over
their future career. In addition, young investigators may feel the need to increase their
publication list quickly in order to secure their next job or they believe that including more
experienced colleagues as authors will increase their chances of publication. Senior researchers
assign gift authorship as repayment for favors or for encouraging collaboration and maintaining
good working relations. Regardless of the cause, gift authorship is an unacceptable practice for
academic publications.
Ghost authorship: is defined as the failure to award authorship to a person who has contributed
significantly to the research project. Ghost authorship may come about because of differences in
the criteria that junior and senior researchers use to define authorship, a decline in work ethics
during the course of the project or a change in the work environment. Contributors who leave the
project before its closure are often deprived of authorship. Regardless of the cause, ghost
authorship is an unacceptable practice for academic publications.
Co-authorship between Faculty and Students: General principles
Authorship is not presumed to be a right obtained by association with a research project, without
significant contribution. It is to everyone's benefit that there is a clear understanding about
potential joint authorship roles whenever there is research collaboration among faculty and
students, whether the latter are assigned as apprentices, students in a class, hired assistants, or
any other role. Initial arrangements can always be re-discussed should circumstances change; for
example, if the student contributes more to the project than originally anticipated.
1
Principal authorship and other publication credits must accurately reflect the
relative scientific or professional contributions of the individuals involved,
regardless of their relative status.
30 | P a g e
___________________________________________
Research Policies
2
Under no circumstance may a student at SCM publish data owned by SCM or
SCM faculty without permission from the relevant body or faculty member for the
relevant project.
3
The person who conceptualized the project, secured the funding, developed the
research instruments, etc., should review any publication or other public
presentation from the project and give his/her permission if something from the
project is to be published without his or her name on it.
4
A student is presumed to have authorship of his or her master’s thesis and/or
doctoral dissertation and is encouraged to publish any part or all of the approved
thesis or dissertation unless there have been some prior restrictions to which the
student has agreed (e.g. that authorship must be shared with others contributing to
the project or to wait for a jointly authored or edited book combining several
theses). However, students must inform the supervisors of their intention to
publish.
5. If a student expects to be sole author on publications based on all or part of his/her
thesis research, this should be discussed in advance with the supervisor and an
early agreement in writing must be reached.
6. When a significant amount of additional research is required to produce
publishable material, or when the student contributes little to the writing of the
paper, the supervisor may be the first author. Its up to the supervisor to make the
student write up his own work. In basic sciences the supervisor is ALWAYS the
last author known as the senior author and is usually the corresponding author.
7. When a group of students work together on a project and their relative
contributions are equal, they should consider representing themselves by a
collective title, or list the names alphabetically with a qualifying statement that
the contributions are equal. The requirements of the journal itself will determine
the relevant option.
8. Individuals who are not enrolled in a graduate program but are employed as
research assistants should not expect joint authorship of their supervisor's
publications, unless they have made a significant original contribution to the
research program.
9. Data gathered for a research project or a program of research under a PI (using a
grant or otherwise) may not be used by students or collaborators without the PI's
permission, unless they have been made part of a public archive. In either case,
proper acknowledgements are imperative.
31 | P a g e
___________________________________________
Research Policies
10. It is impossible to anticipate all potential problems. Mutual respect, trust and clear
communication forestall difficulties. Please refer to the ‘Dispute Resolution’
section below for further direction.
Dispute Resolution:
If a dispute or concern arises with respect to authorship, the student, researcher and his/her
supervisor should first try to resolve any differences amicably. If a discussion with the supervisor
does not resolve the problem, several avenues of dispute resolution within the student’s/
researcher’s section can be approached in the following order:
Head of the section
Research Center
IRB/EC
Strategy for determining authorship
As scientific research becomes more multi-disciplinary in nature, individual contributions of all
authors must be specified and perhaps a strategy for assigning credit when publishing should be
adopted. The procedure developed by Digiusto, 1994, and Ahmed et al., 1997 can serve as
guidelines and details can be obtained from research and training center.
32 | P a g e
___________________________________________
Research Policies
4- FINANCIAL ASPECTS OF RESEARCH PROPOSAL
4.1 BUDGET
1
All research proposals incur (overhead) costs subject to the use of various hospital facilities
during the course of the project (It is very unusual for any research project that involves
human subjects requiring clinical care to carry Zero budget!).
2
These expenses are the consequence of using various hospital/college services needed over
and above that which are offered routinely to a patient with the same medical condition who
is not a study participant.
3
Identifying an estimated budget cost will enable companies supporting research to fund the
project appropriately. For this reason it is very important to get advice regarding the
overhead cost estimation, which should include also the various hospital services, used for
the study.
4.2 FUNDING SOURCES
The Research Department shall offer funding for the research projects if and when
appropriate.
The other potential sponsors are:
Pharmaceutical Industry (profit institutions).
National and International Granting bodies in Pakistan and abroad.
Other donor/sponsorship sources (non-profit organizations).
Individuals (e.g. private patients).
4.3 RECEIPT & DISBURSEMENT OF RESEARCH FUNDS
1
For self directed research with no contractual obligation for defined outcomes, grant money
should go to the Research Center account for disbursement to the PI and indirect costs be
charged at an agreed percentage and rest given on as needed basis to PI and the study team
but no direct remuneration to be paid to the PI by the Sponsoring organization.
2
If the grant is contractual (government, private sector) setting specific terms regarding
research outcomes and proprietary rights, then an agreed percentage overhead will be
charged and rest should be used for direct costs and remuneration to PI and the study related
staff at a predetermined rate.
33 | P a g e
___________________________________________
3
Research Policies
The revenue from overheads should be distributed to college/university administration,
research center, and department to which PI belong at an agreed rate.
4.4 COST ESTIMATION
(Please complete FORM-C for cost estimation)
In order to know ways how to handle overhead costs for a research project estimation of
overhead cost and subsequent management of generated funds for a research proposal should
include:
1
Pathology and laboratory investigations.
2
Other diagnostic studies (Cardiopulmonary, EEG, ECHO, etc.).
3
Medical imaging procedures.
4
Pharmacy-including drug dispensing costs.
5
Clinic visits.
6
Physician’s time and input.
7
Nursing Services.
8
SCMRC costs
9
Patient related costs (transportation, etc.).
10
Other costs.
11
An approved price list for the above will be available at the Research office. In addition the
list will be available for each section head.
12
The cost of various procedures relevant to the proposed research will be provided to the
principal investigator on request through the chairman or head of his/her section.
13
Research proposals not funded by external donor organizations should be charged at actual
cost of consumable and incurred cost born by the sponsor (see please next point).
4.5 RESEARCH FUND MANAGEMENT
To allow the Research center to monitor funds made available by funding agencies,
the following policies and procedures should be considered:
34 | P a g e
___________________________________________
Research Policies
1
All funds generated through industry or other donor bodies should be received and
accounted for by Research Office assigned budget/accounts office (financial audit).
2
A Research Cost Centre has been established for this reason.
3
All agreements/ contracts/MOU’s will be signed between the Research Office on behalf of
the institution and the Sponsoring Organization. All payments/grants/funds will be received
in the name of “Shifa Foundation” which will be deposited in the Research Fund and then
disbursed as per section 5.3. The Agreements/Contracts/MOU’s should have the signatures
of the concerned Principal Investigator along with the relevant departments approval
involved in the services.
4
Generated funds from support services will be utilized to support the costs
services (future researchers and/or needs for the services i.e. equipment).
of such
4.6 AGREEMENTS/CONTRACTS/MOU’s
1. All Agreements/Contracts/MOU’s shall be signed and negotiated by the Research Office
and the Sponsoring Organizations.
2. Research Office shall mediate all correspondences between the P.I and the Sponsoring
Organizations.
3. An Agreement will be signed between the Research Office and the P.I for all sponsored
research outlining various financial heads.
35 | P a g e
___________________________________________
Research Policies
5. NON-FACULTY RESEARCH APPOINTMENTS
RESEARCH MEDICAL OFFICERS
All Medical Officers hired for Research activities and any other study related staff shall
be appointed/hired directly by the Research Office. Functional and administrative
reporting of all Research Medical Officers and other research related staff will also be to
the Research Office.
Projects/tasks will be assigned by the Research Office to the RMO’s who in turn
will work in close collaboration with the concerned Consultants for successful initiation
and timely completion of the proposed research studies.
All RMO’s will be required to submit weekly reports of study progress to the
Research Office
Note: All study related appointments (when and if required after careful assessing the
need by the Research Office) will be made by the Research Office in an
open and transparent fashion after being approved by the Medical Director.
ADMINISTRATIVE SUPPORT STAFF AND LOGISTICS/EQUIPMENT
The Research Office will formulate a competent team which will assist in day to day
operations and functioning of the Research Office.
36 | P a g e
___________________________________________
Research Policies
6. REGULATORY COMPLIANCE
WORLD MEDICAL ASSOCIATION DECLARATION OF HELSINKI
Introduction
1
The World Medical Association has developed the Declaration of Helsinki as a statement of
ethical principles to provide guidance to physicians and other participants in medical
research involving human subjects. Medical research involving human subjects includes
research on identifiable human material or identifiable data.
It is the duty of the physician to promote and safeguard the health of the people. The
physician's knowledge and conscience are dedicated to the fulfillment of this duty.
The Declaration of Geneva of the World Medical Association binds the physician with the
words, "The health of my patient will be my first consideration," and the International Code
of Medical Ethics declares that, "A physician shall act only in the patient's interest when
providing medical care which might have the effect of weakening the physical and mental
condition of the patient."
Medical progress is based on research which ultimately must rest in part on experimentation
involving human subjects.
In medical research on human subjects, considerations related to the well-being of the
human subject should take precedence over the interests of science and society.
The primary purpose of medical research involving human subjects is to improve
prophylactic, diagnostic and therapeutic procedures and the understanding of the etiology
and pathogenesis of disease. Even the best proven prophylactic, diagnostic, and therapeutic
methods must continuously be challenged through research for their effectiveness,
efficiency, accessibility and quality.
In current medical practice and in medical research, most prophylactic, diagnostic and
therapeutic procedures involve risks and burdens.
Medical research is subject to ethical standards that promote respect for all human beings
and protect their health and rights. Some research populations are vulnerable and need
special protection. The particular needs of the economically and medically disadvantaged
must be recognized. Special attention is also required for those who cannot give or refuse
consent for themselves, for those who may be subject to giving consent under duress, for
those who will not benefit personally from the research and for those for whom the research
is combined with care.
Research Investigators should be aware of the ethical, legal and regulatory requirements for
research on human subjects in their own countries as well as applicable international
requirements. No national ethical, legal or regulatory requirement should be allowed to
reduce or eliminate any of the protections for human subjects set forth in this Declaration.
2
3
4
5
6
7
8
9
Basic Principles For All Medical Research
1
It is the duty of the physician in medical research to protect the life, health, privacy, and
dignity of the human subject.
2. Medical research involving human subjects must conform to generally accepted scientific
principles, be based on a thorough knowledge of the scientific literature, other relevant
37 | P a g e
___________________________________________
Research Policies
sources of information, and on adequate laboratory and, where appropriate, animal
experimentation.
3. Appropriate caution must be exercised in the conduct of research which may affect the
environment, and the welfare of animals used for research must be respected.
4. The design and performance of each experimental procedure involving human subjects
should be clearly formulated in an experimental protocol. This protocol should be
submitted for consideration, comment, guidance, and where appropriate, approval to a
specially appointed ethical review committee, which must be independent of the
investigator, the sponsor or any other kind of undue influence. This independent committee
should be in conformity with the laws and regulations of the country in which the research
experiment is performed. The committee has the right to monitor ongoing trials. The
researcher has the obligation to provide monitoring information to the committee,
especially any serious adverse events. The researcher should also submit to the committee,
for review, information regarding funding, sponsors, institutional affiliations, other
potential conflicts of interest and incentives for subjects.
5. The research protocol should always contain a statement of the ethical considerations
involved and should indicate that there is compliance with the principles enunciated in this
Declaration.
6. Medical research involving human subjects should be conducted only by scientifically
qualified persons and under the supervision of a clinically competent medical person. The
responsibility for the human subject must always rest with a medically qualified person and
never rest on the subject of the research, even though the subject has given consent.
7. Every medical research project involving human subjects should be preceded by careful
assessment of predictable risks and burdens in comparison with foreseeable benefits to the
subject or to others. This does not preclude the participation of healthy volunteers in
medical research. The design of all studies should be publicly available.
8. Physicians should abstain from engaging in research projects involving human subjects
unless they are confident that the risks involved have been adequately assessed and can be
satisfactorily managed. Physicians should cease any investigation if the risks are found to
outweigh the potential benefits or if there is conclusive proof of positive and beneficial
results.
9. Medical research involving human subjects should only be conducted if the importance of
the objective outweighs the inherent risks and burdens to the subject. This is especially
important when the human subjects are healthy volunteers.
10. Medical research is only justified if there is a reasonable likelihood that the populations in
which the research is carried out stand to benefit from the results of the research.
11. The subjects must be volunteers and informed participants in the research project.
12. The right of research subjects to safeguard their integrity must always be respected. Every
precaution should be taken to respect the privacy of the subject, the confidentiality of the
patient's information and to minimize the impact of the study on the subject's physical and
mental integrity and on the personality of the subject.
13. In any research on human beings, each potential subject must be adequately informed of
the aims, methods, sources of funding, any possible conflicts of interest, institutional
affiliations of the researcher, the anticipated benefits and potential risks of the study and the
discomfort it may entail. The subject should be informed of the right to abstain from
participation in the study or to withdraw consent to participate at any time without reprisal.
38 | P a g e
___________________________________________
Research Policies
After ensuring that the subject has understood the information, the physician should then
obtain the subject's freely-given informed consent, preferably in writing. If the consent
cannot be obtained in writing, the non-written consent must be formally documented and
witnessed.
14. When obtaining informed consent for the research project the physician should be
particularly cautious if the subject is in a dependent relationship with the physician or may
consent under duress. In that case the informed consent should be obtained by a wellinformed physician who is not engaged in the investigation and who is completely
independent of this relationship.
15. For a research subject who is legally incompetent, physically or mentally incapable of
giving consent or is a legally incompetent minor, the investigator must obtain informed
consent from the legally authorized representative in accordance with applicable law.
These groups should not be included in research unless the research is necessary to
promote the health of the population represented and this research cannot instead be
performed on legally competent persons.
16. When a subject deemed legally incompetent, such as a minor child, is able to give assent to
decisions about participation in research, the investigator must obtain that assent in addition
to the consent of the legally authorized representative.
17. Research on individuals from whom it is not possible to obtain consent, including proxy or
advance consent, should be done only if the physical/mental condition that prevents
obtaining informed consent is a necessary characteristic of the research population. The
specific reasons for involving research subjects with a condition that renders them unable
to give informed consent should be stated in the experimental protocol for consideration
and approval of the review committee. The protocol should state that consent to remain in
the research should be obtained as soon as possible from the individual or a legally
authorized surrogate.
18. Both authors and publishers have ethical obligations. In publication of the results of
research, the investigators are obliged to preserve the accuracy of the results. Negative as
well as positive results should be published or otherwise publicly available. Sources of
funding, institutional affiliations and any possible conflicts of interest should be declared in
the publication. Reports of experimentation not in accordance with the principles laid down
in this Declaration should not be accepted for publication.
Additional Principles For Medical Research Combined With Medical Care
1. The physician may combine medical research with medical care, only to the extent that the
research is justified by its potential prophylactic, diagnostic or therapeutic value. When
medical research is combined with medical care, additional standards apply to protect the
patients who are research subjects.
39 | P a g e
___________________________________________
Research Policies
2. The benefits, risks, burdens and effectiveness of a new method should be tested against
those of the best current prophylactic, diagnostic, and therapeutic methods. This does not
exclude the use of placebo, or no treatment, in studies where no proven prophylactic,
diagnostic or therapeutic method exists.1
3. At the conclusion of the study, every patient entered into the study should be assured of
access to the best proven prophylactic, diagnostic and therapeutic methods identified by the
study.2
4. The physician should fully inform the patient which aspects of the care are related to the
research. The refusal of a patient to participate in a study must never interfere with the
patient-physician relationship.
5. In the treatment of a patient, where proven prophylactic, diagnostic and therapeutic methods
do not exist or have been ineffective, the physician, with informed consent from the patient,
must be free to use unproven or new prophylactic, diagnostic and therapeutic measures, if in
the physician's judgment it offers hope of saving life, re-establishing health or alleviating
suffering. Where possible, these measures should be made the object of research, designed
to evaluate their safety and efficacy. In all cases, new information should be recorded and,
where appropriate, published. The other relevant guidelines of this Declaration should be
followed.
6.2
ENVIORENMENTAL HEALTH AND SAFETY
Biohazard in Research
Introduction
Research may involve biohazardous agents and may generate biohazardous waste. This
section pertains to the safe handling, and disposal of such materials.
Definition
A biological hazard, also known as a biohazard, is an organism or a by-product from an
organism that is harmful or potentially harmful to other living things, primarily human
beings in that it is potentially infectious.
Common types of biological hazards include bacteria, viruses, or toxins that were
created by a particular organism or microorganism. The "biohazard symbol" is a familiar
sight in hospitals, and any object that carries it should be treated with extreme caution.
Biohazard Symbol
40 | P a g e
___________________________________________
Research Policies
Biohazard Levels:
The United States' Center for Disease Control and Prevention
http://en.wikipedia.org/wiki/Centers_for_Disease_Control_and_Prevention (CDC) categorizes
various diseases in levels of biohazard, Level 1 being minimum risk and Level 4 being
extreme risk.
Biohazard Level 1: Bacteria and viruses including Bacillus subtilis , canine hepatitis,
E.coli, varicella ( chicken pox), as well as some cell cultures and non-infectious bacteria.
At this level precautions against the biohazardous materials in question are minimal, most
likely involving gloves and some sort of facial protection. Usually, contaminated
materials are left in open (but separately indicated) waste receptacles. Decontamination
procedures for this level are similar in most respects to modern precautions against
everyday viruses (i.e. washing one's hands with anti-bacterial soap, washing all exposed
surfaces of the lab with disinfectants, etc.). In a lab environment, all materials used for
cell and/or bacteria cultures are decontaminated via autoclave.
Biohazard Level 2: Bacteria and viruses that cause only mild disease to humans, or are
difficult to contract via aerosol in a lab setting, such as hepatitis A, B, and C, influenza A,
Lyme disease, salmonella, mumps, measles, scrapie, dengue fever, and HIV. Routine
diagnostic work with clinical specimens can be done safely at Biosafety Level 2, using
Biosafety Level 2 practices and procedures. Research work (including co-cultivation,
virus replication studies, or manipulations involving concentrated virus) can be done in a
BSL-2 (P2) facility, using BSL-3 practices and procedures.
Biohazard Level 3: Bacteria and viruses that can cause severe to fatal disease in humans,
but for which vaccines or other treatments exist, such as anthrax, West Nile virus, SARS
virus, variola virus (smallpox), tuberculosis, typhus, Rift Valley fever, Rocky Mountain
Spotted fever , yellow fever and malaria. Among parasites Plasmodium falciparum
which causes Malaria, and Trypanosoma cruzi, which causes trypanosomiasis, also come
under this level.
Biohazard Level 4: Viruses and bacteria that cause severe to fatal disease in humans,
and for which vaccines or other treatments are not available, such as Bolivian and
Argentine hemorrhagic fevers, Dengue hemorrhagic fever, Marburg virus, Ebola virus,
hantaviruses, Lassa fever, Crimean-Congo hemorrhagic fever, and other hemorrhagic
diseases. When dealing with biological hazards at this level the use of a Hazmat suit and
41 | P a g e
___________________________________________
Research Policies
a self-contained oxygen supply is mandatory. The entrance and exit of a Level Four
biolab will contain multiple showers, a vacuum room, an ultraviolet light room,
autonomous detection system, and other safety precautions designed to destroy all traces
of the biohazard. Multiple airlocks are employed and are electronically secured to prevent
both doors opening at the same time. All air and water service going to and coming from
a Biosafety Level 4 (P4) lab will undergo similar decontamination procedures to
eliminate the possibility of an accidental release.
Biosafety Levels:
Biosafety Level 1:
This level is suitable for work involving well-characterized agents not known to
consistently cause disease in healthy adult humans, and of minimal potential hazard to
laboratory personnel and the environment ( mentioned as Biohazard Level 1).
Precautions against the biohazardous materials in question are minimal as mentioned in
para above. Laboratory personnel have specific training in the procedures conducted in
the laboratory and are supervised by a scientist with general training in microbiology or a
related science.
Biosafety Level2: This level is similar to Biosafety Level 1 and is suitable for work
involving agents of moderate potential hazard to personnel and the environment (
mentioned as Biohazard Level 2) . It requires that:
1. laboratory personnel have specific training in handling pathogenic agents and are
directed by scientists with advanced training;
2. access to the laboratory is limited when work is being conducted
3. extreme precautions are taken with contaminated sharp items
4. certain procedures in which infectious aerosols or splashes may be created are
conducted in biological safety cabinets or other physical containment equipment
Biosafety Level 3
This level is applicable to clinical, diagnostic, teaching, research, or production facilities
in which work is done with indigenous or exotic agents which may cause serious or
potentially lethal disease after inhalation. It includes various bacteria, parasites and
viruses that can cause severe to fatal disease in humans but for which treatments exist,
such as Leishmania, Mycobacterium tuberculosis, Bacillus anthracis, Chlamydophila
psittaci, as well as viruses mentioned above ( Biohazard Level 3).
All procedures involving the manipulation of infectious materials are conducted within
biological safety cabinets, specially designed hoods, or other physical containment
devices, or by personnel wearing appropriate personal protective clothing and equipment.
The laboratory has special engineering and design features.
It is recognized, however, that some existing facilities may not have all the facility
features recommended for Biosafety Level 3 (i.e., double-door access zone and sealed
penetrations). In this circumstance, an acceptable level of safety for the conduct of
routine procedures, (e.g., diagnostic procedures involving the propagation of an agent for
identification, typing, susceptibility testing, etc.), may be achieved in a biosafety level 2
(P2) facility, providing:
42 | P a g e
___________________________________________
Research Policies
1. the filtered exhaust air from the laboratory room is discharged to the outdoors,
2. the ventilation to the laboratory is balanced to provide directional airflow into the
room,
3. access to the laboratory is restricted when work is in progress, and
4. the recommended Standard Microbiological Practices, Special Practices, and Safety
Equipment for Biosafety Level 3 are rigorously followed.
Biosafety Level 4
This level is required for work with dangerous and exotic agents that pose a high
individual risk of aerosol-transmitted laboratory infections, agents which cause severe to
fatal disease in humans for which vaccines or other treatments are not available (
mentioned above as Biohazard Level 4). Safety measures are mentioned above.
Agents with a close or identical antigenic relationship to Biosafety Level 4 agents are
handled at this level until sufficient data is obtained either to confirm continued work at
this level, or to work with them at a lower level.
Members of the laboratory staff have specific and thorough training in handling
extremely hazardous infectious agents and they understand the primary and secondary
containment functions of the standard and special practices, the containment equipment,
and the laboratory design characteristics. They are supervised by qualified scientists who
are trained and experienced in working with these agents. Access to the laboratory is
strictly controlled by the laboratory director.
The facility is either in a separate building or in a controlled area within a building, which
is completely isolated from all other areas of the building. A specific facility operations
manual is prepared or adopted. Building protocols for preventing contamination often use
negatively pressurized facilities, which, if compromised, would severely inhibit the
containment of an outbreak of aerosol pathogens.
Within work areas of the facility, all activities are confined to Class III biological safety
cabinets, or Class II biological safety cabinets used with one-piece positive pressure
personnel suits ventilated by a life support system.
Biohazardous Waste
Biohazardous waste, also called infectious waste or biomedical waste, is any waste
containing infectious materials or potentially infectious substances such as blood. Of
special concern are sharp wastes such as needles, blades, glass pipettes, and other wastes
that can cause injury during handling. The biohazardous waste generated may also
contain radioactive material and/or hazardous chemicals.
Types of Biohazardous Waste
Biohazardous waste includes the following materials:
1. Human blood and blood products: All human blood, blood products (such as
serum, plasma, and other blood components) in liquid or semi-liquid form. Items
contaminated with blood that, if compressed, would release blood in a liquid or semi-
43 | P a g e
___________________________________________
Research Policies
liquid form, or items caked with dried blood capable of being released during
handling.
2. Human Body Fluids: Human body fluids in a liquid or semi-liquid state, including:
semen, vaginal secretions, cerebral spinal fluid, synovial fluid, pleural fluid,
pericardial fluid, peritoneal fluid, amniotic fluid, and saliva from dental procedures.
Also includes any other human body fluids visibly contaminated with blood.
3. Microbiological Wastes: Laboratory wastes containing or contaminated with
concentrated forms of infectious agents. Such waste includes discarded specimen
cultures, stocks of etiologic agents, discarded live and attenuated viruses, blood or
body fluids known to contain infectious pathogens, wastes from the production of
biologicals and serums, disposable culture dishes, and devices used to transfer,
inoculate and mix cultures.
4. Pathological waste: All human tissues, organs, and body parts, including waste
biopsy materials, tissues, and anatomical parts from surgery, procedures, or autopsy.
Any unfixed human tissue, except skin.
5. Animal waste: All animal carcasses, body parts, and any bedding material from
animals known to be infected with, or that have been inoculated with human
pathogenic microorganisms infectious to humans.
6. Sharps waste: Includes needles, blades etc contaminated with blood or above
mentioned hazardous waste . As these items may cause injury special precautions are
required for their disposal .They must be treated, packaged, labelled, and transported
in separate labelled containers.
Responsibilities of Researcher
Research protocols that generate bio hazardous waste must incorporate the following:
1.
Steps ensuring that the waste is correctly treated and disposed off.
2.
Packaging of the waste to prevent exposure or injury (needle sticks, cuts) to
anyone handling the waste.
3.
Labelling of the waste with the research project’s / researchers name and
location within the hospital.
Biohazard Waste Minimization
Biohazard waste bags should be used for bio hazardous materials only and not for regular
trash. Disposal of non-biohazard waste in a biohazard waste container adds significant
costs to waste management.
44 | P a g e
___________________________________________
Research Policies
The following are examples of items that do not need to be disposed as biohazard waste:
1.
Gloves used to handle containers of blood or body fluids;
2.
Paper towels or bench paper on which containers of blood or body fluids may
have been placed but did not spill.
3.
Any other material used to handle blood indirectly but that did not come into
direct contact with the blood.
Disinfecting and Disposing of Bio hazardous Liquids
Bio hazardous liquids and liquids that contain human blood should be disinfected and
flushed down the drain.
Do not attempt to disinfect solutions that contain a large amount of whole blood to avoid
clot formation.
To disinfect small amounts:
1. Add a disinfectant such as Wescodyne (iodophor) or Clorox (hypochlorite) until the
solution of disinfectant and waste liquid is one part disinfectant to five parts waste
liquid.
2. Make sure there are no bubbles in the solution.
3. Let the solution stand for at least 30 minutes.
4. Pour the solution down the drain with cold water.
5. If using any other disinfectant solution ensure recommended contact time.
Preparing Bio hazardous Waste for Autoclaving or Disposal
Bio hazardous (infectious) wastes that cannot be treated as above include large amounts
of protein or clotted blood. Containers of protein, stock solutions, clotted blood, etc.,
should be steam-sterilized in an infectious waste autoclave dedicated for this
purpose.
Labelling
Each bag of bio hazardous waste must be labelled with:
1. The department /location/ room in which the waste was generated, and
2. The date the waste was packaged.
Using a permanent marker the information should be written directly on the waste bag.
Packaging
Dry, solid bio hazardous waste must be placed in an autoclave bag. Bags should be
closed or covered when not in use or at the end of the day.
Do not fill bag more than halfway to allow for a five-inch grip. Tie the bag tightly before
transporting.
45 | P a g e
___________________________________________
Research Policies
Transporting
Bio hazardous waste to be autoclaved must be transported to an autoclave within 14 days
of first generating the waste. The use of a cart is recommended for transporting biohazard
waste.
All bags must be deposited in red, covered holding containers. The waste must be logged
in at the autoclave room in a logbook.
Plastic Pipette Disposal
Plastic pipettes may be used in many laboratory based research projects. When
contaminated, they may be safely disposed of in either an autoclave bag or a sharps
container. If not contaminated, intact plastic pipettes should be disposed of in a
laboratory glass box for disposal in regular garbage,
Bag Disposal of Plastic Pipettes Contaminated with Biohazardous Material
To dispose of contaminated plastic pipettes in a bag, the pipettes must be intact, placed
in clear autoclave biohazard bags and double-bagged. A broken plastic pipette is always
considered a sharp, and therefore must be disposed of in a sharps container.
Sharps Waste
Sharps include:
1. Needles (whether or not attached to a syringe or covered by a plastic guard);
2. IV tubing with needle attached;
3. Glass Pasteur pipettes;
4. Disposable glass pipettes;
5. Glass slides and cover slips;
6. Scalpels, razor blades, and lancets; and
7. Broken glass and splintered plastic, when contaminated with blood or other potentially
infectious material.
Non-contaminated broken lab glass and plastic such as beakers and bottles are NOT
considered sharps for disposal purposes.
Categories of Sharps Waste
Sharps waste categories include:
1. Sharps, which are either contaminated or not contaminated with biological material;
2. Radioactive sharps, which are sharps contaminated with radioactive material; and
46 | P a g e
___________________________________________
Research Policies
3. Chemical sharps (e.g. broken mercury thermometers, or syringes contaminated with
chemotherapy drugs).
Laboratory glassware is not considered sharps waste for disposal purposes, but may be
sharp enough to puncture normal garbage bags and endanger waste handlers. Lab glass
includes items such as broken glass beakers or bottles, plastic pipettes and pipette tips.
Sharps Waste Minimization
Although sharps containers are often conveniently placed throughout the hospital, it is
important to remember these containers are for sharps waste only, and are not to be used
for non-sharp biohazard waste or regular trash. Disposal of non-sharp biohazard waste in
a sharps container adds significant costs to waste management.
The following are examples of items that should not be disposed of as sharps waste:
1. Gloves;
2. Paper towels;
3. Lab glass (includes plastic pipettes and pipette tips);
4. Chemical bottles;
5. Petri dishes or culture plates
6. Plastic vials and conical tubes.
Sharps Waste Disposal Procedures
Sharps are collected in standard sharps containers. The standard (non-radioactive, nonchemical) sharps waste pickup procedure is as follows:
1. When sharps container is 2/3 to 3/4 full, secure the lid.
2. With a permanent marker, write the project name, number, location and date on the
sharp container.
3. Place the sharps container in the hallway for pickup by Housekeeping staff.
Radioactive Sharps Waste Disposal Procedures
Radioactive sharps are collected in standard sharps containers
1. It should be labelled with a radioactive waste label,
2. When possible, isotopes should be segregated in separate radioactive sharps containers.
3. When sharps container is 2/3 to 3/4 full, secure the lid.
4. Arrange for disposal according to existing hospital/ national protocol.
Chemical Sharps Waste Disposal Procedures
Chemical sharps such as broken mercury thermometers or syringes contaminated with
chemotherapy agents must not be disposed of in regular red sharps containers.
Special Instructions for Residual Cytotoxic Waste
47 | P a g e
___________________________________________
Research Policies
Residual cytotoxic waste is any item contaminated with chemotherapy agents, also called
antineoplastic or chemotherapeutic agents. Such items most often include contaminated
needles, vials, intravenous tubing, bottles and bags, linen, masks, gloves, and lab coats.
Wastes containing more than residual amounts (such as non-empty vials or syringes)
must be segregated and collected as hazardous chemical waste as described above
Residual cytotoxic waste must be separated and disposed of differently from other
hazardous chemical wastes and biohazard waste.
Accumulation
Solids, including sharps, contaminated with residual cytotoxic wastes should be collected
in rigid plastic yellow chemotherapy waste containers or other properly-labelled rigid and
leak proof containers. Standard red sharps containers must not be used. Yellow
chemotherapy waste bins should be available.
Labelling
If using a container other than a yellow chemotherapy waste container, it must be clearly
labelled Residual Cytotoxic Waste. All containers must be labelled with the project,
patient ID date, and location.
Collection
When the box is full, secure the lid for pickup. Do not place the container in the hallway,
and do not autoclave cytotoxic waste.
Disposal options for Cytotoxic Waste
Incineration at high temperatures:
Full destruction of all cytotoxic substances may require temperature up to 1200°C.
Incineration at lower temperatures may result in the release of hazardous cytotoxic
vapours into the atmosphere. Modern double-chamber pyrolytic incinerators are suitable,
provided that a temperature of 1200°C with a minimum gas residence time of 2 seconds
or 1000°C with a minimum gas residence time of five seconds can be achieved in the
second chamber. The incinerator should be fitted with gas cleaning equipment.
Incineration is also possible in rotary kilns designed for thermal decomposition of
chemical wastes, in foundries, or in cement kilns, which usually have furnaces operating
well in excess of 850°C. Incineration is most common by municipal incinerators. Singlechamber incinerators or open-air burning is inappropriate for the disposal of cytotoxic
waste.
Chemical degradation:
Chemical degradation methods which convert cytotoxic compounds into non-toxic/nongenotoxic compounds can be used not only for drug residues but also for cleaning of
contaminated urinals, spillages, and protective clothing. The methods are appropriate for
developing countries. Most of these methods are relatively simple and safe; they include
oxidation by potassium permanganate (KMnO4) or sulfuric acid (H2SO4), denitrozation
by hydrobromic acid (HBr), or reduction by nickel and aluminium. The International
Agency for Research on Cancer (IARC) may be contacted for further information.
48 | P a g e
___________________________________________
49 | P a g e
Research Policies
___________________________________________
Research Policies
7 OTHERS
1.1 INFORMED CONSENT
GUIDELINES FOR DRAFTING AN INFORMED CONSENT FORM
A. Basic elements of informed consent in seeking informed consent the following
information shall be provided to each subject:
(1) A statement that the study involves research, an explanation of the purposes of the
research and the expected duration of the subject's participation, a description of the
procedures to be followed, and identification of any procedures which are experimental.
(2) A description of any reasonably foreseeable risks or discomforts to the subject.
(3) A description of any benefits to the subject or to others which may reasonably be
expected from the research.
(4) A disclosure of appropriate alternative procedures or courses of treatment, if any, that
might be advantageous to the subject.
(5) A statement describing the extent, if any, to which confidentiality of records identifying
the subject will be maintained.
(6) For research involving more than minimal risk, an explanation as to whether any
compensation and an explanation as to whether any medical treatments are available if
injury occurs and, if so, what they consist of, or where further information may be
obtained.
(7) An explanation of whom to contact for answers to pertinent questions about the research
and research subjects' rights, and whom to contact in the event of a research-related
injury to the subject; and
(8) A statement that participation is voluntary, refusal to participate will involve no penalty
or loss of benefits to which the subject is otherwise entitled and the subject may
discontinue participation at any time without penalty or loss of benefits to which the
subject is otherwise entitled.
50 | P a g e
___________________________________________
Research Policies
B. Additional elements of informed consent. When appropriate, one or more of the
following elements of information shall also be provided to each subject:
(1) A statement that the particular treatment or procedure may involve risks to the subject (or
to the embryo or fetus, if the subject is or may become pregnant) which are currently
unforeseeable.
(2) Anticipated circumstances under which the subject's participation may be terminated by
the investigator without regard to the subject's consent.
(3) Any additional costs to the subject that may result from participation in the research.
(4) The consequences of a subject's decision to withdraw from the research and procedures
for orderly termination of participation by the subject.
(5) A statement that significant new findings developed during the course of the research
which may relate to the subject's willingness to continue participation will be provided to
the subject; and.
(6) The approximate number of subjects involved in the study
Note: All Informed Consent Forms must be in English and Urdu language or any other
language that the subject understands
51 | P a g e
___________________________________________
Research Policies
7.2 CHECK LIST FOR COMPLETION OF INFORMED CONSENT FORM
A statement that the study involves research
An explanation of the purposes of the research
The expected duration of the subject's participation
A description of the procedures to be followed
Identification of any procedures which are experimental
A description of any reasonably foreseeable risks or discomforts to the subject
A description of any benefits to the subject or to others which may reasonably be expected from the research
A disclosure of appropriate alternative procedures or courses of treatment, if any, that might be advantageous to
the subject
A statement describing the extent, if any, to which confidentiality of records identifying the subject will be
maintained
For research involving more than minimal risk, an explanation as to whether any compensation, and an
explanation as to whether any medical treatments are available, if injury occurs and, if so, what they consist of,
or where further information may be obtained
Research Qs
An explanation of whom to contact for answers to pertinent questions about the research and research subjects'
rights, and whom to contact in the event of a research-related injury to the subject
Rights Qs
Injury Qs
A statement that participation is voluntary, refusal to participate will involve no penalty or loss of benefits to
which the subject is otherwise entitled, and the subject may discontinue participation at any time without penalty
or loss of benefits, to which the subject is otherwise entitled
Additional elements, as appropriate
A statement that the particular treatment or procedure may involve risks to the subject (or to the embryo or fetus,
if the subject is or may become pregnant), which are currently unforeseeable
Anticipated circumstances under which the subject's participation may be terminated by the investigator without
regard to the subject's consent
Any additional costs to the subject that may result from participation in the research
The consequences of a subject's decision to withdraw from the research and procedures for orderly termination of
participation by the subject
A statement that significant new findings developed during the course of the research, which may relate to the
subject's willingness to continue participation, will be provided to the subject
The approximate number of subjects involved in the study
52 | P a g e
___________________________________________
Research Policies
7.3 RESEARCH INVOLVING PREGNANT WOMEN OR FETUSES
Pregnant women or fetuses may be involved in research if all of the following conditions are
met:
(a) Where scientifically appropriate, preclinical studies, including studies on pregnant animals,
and clinical studies, including studies on non-pregnant women, have been conducted and provide
data for assessing potential risks to pregnant women and fetuses.
(b) The risk to the fetus is caused solely by interventions or procedures that hold out the prospect
of direct benefit for the woman or the fetus; or, if there is no such prospect of benefit, the risk to
the fetus is not greater than minimal and the purpose of the research is the development of
important biomedical knowledge which cannot be obtained by any other means.
(c) Any risk is the least possible for achieving the objectives of the research.
(d) If the research holds out the prospect of direct benefit to the pregnant woman, the prospect of
a direct benefit both to the pregnant woman and the fetus, or no prospect of benefit for the
woman nor the fetus when risk to the fetus is not greater than minimal and the purpose of the
research is the development of important biomedical knowledge that cannot be obtained by any
other means, her consent is obtained in accord with the informed consent provisions of subpart A
of this part;
(e) If the research holds out the prospect of direct benefit solely to the fetus then the consent of
the pregnant woman and the father is obtained in accord with the informed consent provisions of
subpart A of this part, except that the father's consent need not be obtained if he is unable to
consent because of unavailability, incompetence, or temporary incapacity or the pregnancy
resulted from rape or incest.
(f) Each individual providing consent under paragraph (d) or (e) of this section is fully informed
regarding the reasonably foreseeable impact of the research on the fetus or neonate;
(g) For children who are pregnant, assent and permission are obtained in accord with the
provisions of subpart D of this part;
(h) No inducements, monetary or otherwise, will be offered to terminate a pregnancy;
(i) Individuals engaged in the research will have no part in any decisions as to the timing,
method, or procedures used to terminate a pregnancy; and
(j) Individuals engaged in the research will have no part in determining the viability of a neonate.
7.4 RESEARCH INVOLVING NEONATES
53 | P a g e
___________________________________________
Research Policies
(a) Neonates of uncertain viability and nonviable neonates may be involved in research if all of
the following conditions are met:
(1) Where scientifically appropriate, preclinical and clinical studies have been conducted and
provide data for assessing potential risks to neonates.
(2) Each individual providing consent under paragraph (b) (2) or (c) (5) of this section is fully
informed regarding the reasonably foreseeable impact of the research on the neonate.
(3) Individuals engaged in the research will have no part in determining the viability of a
neonate.
(4) The requirements of paragraph (b) or (c) of this section have been met as applicable.
(b) Neonates of uncertain viability. Until it has been ascertained whether or not a neonate is
viable, a neonate may not be involved in research covered by this subpart unless the following
additional conditions have been met:
(1) The IRB determines that:
(i) The research holds out the prospect of enhancing the probability of survival of the neonate to
the point of viability, and any risk is the least possible for achieving that objective, or
(ii) The purpose of the research is the development of important biomedical knowledge which
cannot be obtained by other means and there will be no added risk to the neonate resulting from
the research; and
(2) The legally effective informed consent of either parent of the neonate or, if neither parent is
able to consent because of unavailability, incompetence, or temporary incapacity, the legally
effective informed consent of either parent's legally authorized representative is obtained in
accord with subpart A of this part, except that the consent of the father or his legally authorized
representative need not be obtained if the pregnancy resulted from rape or incest
(c) Nonviable neonates. After delivery nonviable neonate may not be involved in research
covered by this subpart unless all of the following additional conditions are met:
(1) Vital functions of the neonate will not be artificially maintained;
(2) The research will not terminate the heartbeat or respiration of the neonate;
(3) There will be no added risk to the neonate resulting from the research;
54 | P a g e
___________________________________________
Research Policies
(4) The purpose of the research is the development of important biomedical knowledge that
cannot be obtained by other means; and
(5) The legally effective informed consent of both parents of the neonate is obtained in accord
with subpart A of this part, except that the waiver and alteration provisions of §46.116(c) and (d)
do not apply. However, if either parent is unable to consent because of unavailability,
incompetence, or temporary incapacity, the informed consent of one parent of a nonviable
neonate will suffice to meet the requirements of this paragraph (c)(5), except that the consent of
the father need not be obtained if the pregnancy resulted from rape or incest. The consent of a
legally authorized representative of either or both of the parents of a nonviable neonate will not
suffice to meet the requirements of this paragraph (c) (5).
(d) Viable neonates. A neonate, after delivery, that has been determined to be viable may be
included in research only to the extent permitted by and in accord with the requirements of
subparts A and D of this part.
7.5 RESEARCH INVOLVING, AFTER DELIVERY, THE PLACENTA, THE DEAD
FETUS OR FETAL MATERIAL
(a) Research involving, after delivery, the placenta; the dead fetus; macerated fetal material; or
cells, tissue, or organs excised from a dead fetus, shall be conducted only in accord with any
applicable local laws and regulations regarding such activities.
(b) If information associated with material described in paragraph (a) of this section is recorded
for research purposes in a manner that living individuals can be identified, directly or through
identifiers linked to those individuals, those individuals are research subjects and all pertinent
subparts of this part are applicable.
55 | P a g e
___________________________________________
Research Policies
7.6 FORM-A
Research Department Ref #
Date
Received
Shifa International Hospital, Shifa College of Medicine&
Shifa College of Nursing
Research APPLICATION FORM
____________________________________________________________________________________
Research Department
Office:
Sector H-8/4 Islamabad
Fax:
Pakistan
Email: [email protected]
Located at Department of Medical Staff Affairs
____________________________________________________________________________________
A. Submission Category: (Please check all that apply).
New Protocol: (Study never performed. Include all documents listed in Section B.)
Renewal or Modifications (Please complete Form “B”)
(Study has previously been approved by IRB. Include the IRB Approval letter.
Check all that apply:
Informed Consent
Protocol
Data Collection Form
Other _______________
Application for
Full Review
Expedite Review
Exempt Review
B. Checklist
Two Copies of Research Proposal Application Form with Checklist
Two Copies of Research Protocol
Two Copies of Data Collection Forms (surveys, questionnaires, telephone scripts, data collection)
Two Copies of Patient Information Sheet and Informed Consent Form English with Urdu
Translation
Curriculum Vitae And/ Or Other Relevant Documents Evidencing Qualifications of Investigator(S)
And Sub-Investigator(S) and all other study team members
Approval from the Departmental Head
Any additional document that require approval
Copy of this application and study documents filed for personal record
56 | P a g e
___________________________________________
Research Policies
A. COVER PAGE
TITLE OF PROPOSAL
TYPE OF PROJECT
Human
Diagnostic
Laboratory
Chart Review
Therapeutic
Others
PRINCIPLE INVESTIGATOR OTHER STUDY TEAM MEMBERS
Principal Investigator: (Person noted as Principal Investigator in the IRB approval notice.)
PI’s Name (Degree)
___________________________________________________________________________
Department & Division ________________________________________________________
Tel No: _______________________
Fax: __________________________
Email: ________________________
Other Study Team Members
Name & Qualification
Title/Position
Department
Signature
B. ABSTRACT
WHAT IS THE SIGNIFICANCE OF THE STUDY? (Please give a brief background of the study)
57 | P a g e
___________________________________________
WHAT ARE THE OBJECTIVES OF THE STUDY?
DESCRIPTION OF METHODS USED IN PROTOCOL
SELECTION CRITERIA (Inclusion& Exclusion Criteria)
58 | P a g e
Research Policies
___________________________________________
Research Policies
DURATION OF THE STUDY
ADVERSE/SERIOUS ADVERSE EFFECTS / POTENTIAL HAZARDS
(Explain how these events would be managed and who will bear the cost?)
POTENTIAL RISK OF THE RESEARCH (To the participating subjects or community as a whole)
59 | P a g e
___________________________________________
Research Policies
POTENTIAL BENEFIT OF THE RESEARCH (To the participating subjects of community as a whole)
C. SOURCE OF FUNDING
Funds Required (Complete Budget Form C)
Sponsored
Please specify the name of the funding source: ___________________________________________
D. SERVICES
Will services at SIH & SCM be utilized which are not considered part of routine medical care?
No
Yes
IF yes please check appropriate box
Cath Lab
Medical Records
Non-Invasive Cardiology
CT Scan Services
MRI
Nursing/Patient Care
General Radiology
Pharmacy
Nuclear Medicine
Laboratory
Ultrasound
Other special Services or Equipment: (please specify) _______________________________
Payment of Arrangements: If “Yes” is checked in the above section, an explanation of payment arrangements is
required and must be included with this submission packet
E. SETTINGS/FACILITIES TO BE USED FOR THE STUDY (In case of multi-centered studies, kindly
list the name of participating centers/countries)
(Please check all that apply)
60 | P a g e
___________________________________________
Inpatient
Research Policies
Outpatient
Shifa Department (Please specify) ___________________________________________
F. EXPLAIN WHAT MEASURES WILL BE TAKEN TO SAFEGUARD PATIENT’S/SUBJECT’S
CONFIDENTIALITY.
G. OTHER STUDY RELATED INFORMATION
H. REFERENCES
I.
DEPARTMENTAL APPROVAL
I agree to accept responsibility for the scientific and technical conduct of the proposed research and
submission of progress reports if this application is approved. I agree to submit study progress report to the
Research Department and inform the IRB of any new information.
PRINCIPLE INVESTIGATOR
NAME: ________________________________________________
SIGNATURE & STAMP ____________________________________
DATE: _________________________________________________
61 | P a g e
___________________________________________
Research Policies
Research Center Ref #
DESIGNATION: __________________________________________
DEPARTMENT: __________________________________________
Date Received
Revision No.
MAILING ADDRESS: ______________________________________
TEL. NO: _______________________________________________
FAX: ___________________________________________________
EMAIL ADD: _____________________________________________
APPROVAL OF DEPARTMENTAL HEAD
I feel that beds and other facilities (if applicable) are adequate. I approve the participation of the concerned
personnel of my department in this study. I hereby approve that there are no potential conflicts within the
department prior to final submission.
NAME: _______________________________________________
SIGNATURE & STAMP: ___________________________________
DATE: ________________________________________________
DESIGNATION: _________________________________________
DEPARTMENT: _________________________________________
MAILING ADDRESS: _____________________________________
TEL NO: ______________________________________________
FAX: _________________________________________________
EMAIL ADD: ___________________________________________
7.7 FORM B
MODIFICATIONS/AMENDMENTS TO RESEARCH PROPOSAL
This form is only applicable for requiring approval on amendments/changes in protocol and other study
documents.
(Please attach the original IRB approval letter along with this form)
62 | P a g e
___________________________________________
Research Policies
Research Department Ref #
STUDY TITLE:
Date
Received
The following documents have amendments (Please attach the list of amendments/changes along
with this form).
Protocol
Data Collection Form
Informed Consent Form
Others ____________________
Principle Investigator
Name: ______________________________________________
Designation: _________________________________________
Department: _________________________________________
Signatures & Stamp: ___________________________________
Date: _______________________________________________
7.8 FORM C
BUDGET FORM (ESTIMATES FOR SUPPORT REQUESTED)
Note: The form should be completed if funds are requested from the Research Department, especially for
those research proposals dealing with human subjects requiring clinical care.
1.
BUDGET
CATEGORY
Laboratory (specify)
2.
Equipment (specify)
S. No
63 | P a g e
REMARKS
ESTIMATED
COSTS
___________________________________________
Research Policies
Research Department Ref #
Date
Received
3.
Radiology
4.
Pharmacy
5.
Clinic Visits
6.
Nursing
7.
Inpatient Days
8.
Supplies
9.
Consultant Fees
10.
Additional Personnel
11.
Patient Costs
12.
Publication Costs
13.
Miscellaneous (specify)
TOTAL
Is there an external sponsor of this study?
YES
NO
If YES, please specify & also provide details of Financial Disclosure ________________________________
7.9 FORM D
POTENTIAL HAZARDS AND TOXICITY
(Please complete this form if there the study involves toxic or hazardous material)
Proposed Title:
______________________________________________________________________________
______________________________________________________________________________
____________________________________________________________
64 | P a g e
___________________________________________
1.
Does the proposed research involve any toxic chemical?
Research Policies
Yes
No
If yes, name chemicals and describe the nature of hazard involved.
____________________________________________________________________________
____________________________________________________________________________
Also indicate how the safety measures will be taken in the use and disposal of these agents.
____________________________________________________________________________
____________________________________________________________________________
2.
Does the proposed research involve any hazardous microorganism? Yes
No
If yes, name the organisms and describe the nature of hazards expected.
____________________________________________________________________________
____________________________________________________________________________
Also describe facilities, safety measures and procedures to protect personnel and environment.
____________________________________________________________________________
____________________________________________________________________________
3.
Does the proposed research involve the radioactive materials?
Yes
No
If yes, describe the materials, half-life and methods of disposal and personnel protection.
_____________________________________________________________________________
65 | P a g e
___________________________________________
Research Policies
_____________________________________________________________________________
4.
Does the proposed research involve recombinant DNA?
Yes
No
If yes, are you familiar with NIH guidelines and do you have the containment
facilities?
Yes
No
Describe the nature of genes to be cloned, organisms and plasmids to be used.
____________________________________________________________________________
Principal Investigator: _____________________________
7.10
Date: ___________________
REGULATORY COMPLIANCE
CORRESPONDENCES
For all Research Projects/studies, communication, correspondences etc. between
researchers and organizations/institutions/companies shall be made through the Research
Office.
CONSULTANTS
We welcome and encourage all faculty/consultants/trainees to come forward with their
ideas for research, or proposals for research to the Research Office for review, discussion
and formulation of an action plan for successful initiation and timely completion of
desired studies.
66 | P a g e
___________________________________________
Research Policies
We shall provide investigators upon communication, with requirements for research in
the form of Research medical officers (after careful assessment of project proposal and
need and approval by the Research Office and the Medical Director) who will aid/assist
the consultants in their research activities.
Your initial communication, i.e. to discuss research projects should be with the head of
the department; upon an acquired approval, a research officer will be assigned to the case.
The officer will aid in the development of a protocol (proposal) for the research project
under supervision of the consultant, and upon completion, this proposal must be approved
by the head of the concerned department and IRB/EC. This will be done in the form of a
document stating that the research proposal has been reviewed and the project has been
given the green signal, signed and dated.
While we recognize that all clinical data pertaining to patients at this hospital are the
brain work of all our consultants, to protect the patients and the consultants all data
review/ collection shall only be made possible after approval of the relevant research
project. These patients are under the care of the doctors at Shifa Intl Hospital Ltd and as
such their clinical data is hospital property; their privacy is our responsibility as is
protecting our consultants. The data belongs to the hospital and reviewing mass amounts
of data shall require permission from the IRB/Research Department.
Should the collected data be of a sensitive nature, its usage shall be restricted to those that
are allowed to view it under the approval of the IRB. All permissions must be
documented for official purposes.
POST GRADUATE RESIDENTS
While we encourage all residents to take part in research activities to broaden their
horizons, all research activity must require co-sponsoring by a consultant/faculty. We
will make ourselves available to help all residents in designing their studies and choosing
the best path for conducting research.
As required for senior doctors, residents/trainees are also not exempt from their share of
paper work and shall be required to submit all documentation for review following
approval of their proposed research.
While we shall make ourselves available to the residents, we encourage residents to write
their own proposals and do their own literature reviews so that they develop and learn
how to formulate study designs for research. For the purpose of data collection, and
analysis we are available.
67 | P a g e
___________________________________________
Research Policies
As and when possible, our center will hold workshops for all residents to help them
strengthen their competency in research, its conduct and publishing articles. We shall
make every effort to involve residents so as to hone their skills in research.
LAB, RADIOLOGICAL, PHARMACY & MEDICAL RECORD
SERVICES
For research projects requiring services like lab, radiology, MRI/CT scan etc a
separate study specific cost code should be created so that study related expenses are not
charged from patients pocket and are charged directly to that specific cost centre.
All labs etc for pure academic studies should be done at a discounted rate.
A Central hospital lab services should be used for all research projects
Shifa local lab should be the lab of priority for all research projects. Utilization
of external labs should only be encouraged when certain tests cannot be
performed locally.
Dedicated Pharmacy services may be assigned for research projects
Dedicated area in the Medical record room may be established to store and archive study
files/documentation.
8- GUIDELINES FOR RESEARCH
WHAT IS RESEARCH?
“Research” is defined as:
"A systematic investigation, including research development, testing and evaluation, designed to
develop or contribute to generalizable knowledge.”
WHY SHOULD ONE CONDUCT RESEARCH?
Conducting research:
Contributes to the greater good of medicine
68 | P a g e
___________________________________________
Research Policies
Expands personal and profession knowledge
Clinical research is a tremendous learning process. Participating in, or conducting research as a
Resident may spark an interest that otherwise may not have been apparent. Going through the
Process may also lead to a greater appreciation for the work and effort involved in the studies
Evaluated and incorporated into one’s practice throughout one’s career.
TYPES OF RESEARCH:
Clinical research comes in two flavors:
i.
ii.
Observational Research
Experimental Research
i. Observational research study:
An observational study is just as it sounds: passive observation of study participants. Participants
can be followed over time, known as a cohort, or be examined at one-point in time, known as
cross-sectional.
Another type of observational study is the case-controlled study. This is typically a case report
comparing those with and without a particular condition. Cohort and case-controlled studies can
be retrospective or prospective.
A retrospective study looks back in time at a defined sample and collects data about predictor
variables after outcomes have occurred.
A prospective study follows events into the future for a select period of time for a sample
defined by the researcher with predictor variables measured before outcomes have occurred and
outcome variables measured as they occur.
Observational studies are passive in that they do not involve manipulation of the variables. A
variable can be what is being measured (outcome), or what helps to define the participants
(predictor). Observational studies often provide data for larger experimental clinical trials.
Cohort studies help provide incidence of a variable, whereas cross-sectional studies provide
prevalence of a variable. Cohort studies can lead to more detailed research design, can provide
data for hypothesis and insight into risk factors.
ii. Experimental research:
In experimental clinical research, we actively manipulate the independent variables and then
69 | P a g e
___________________________________________
Research Policies
measure the effects of this manipulation on the dependent variables2. Experimental clinical
research studies tend to assess the effectiveness of an intervention.
A randomized, blinded trial is the gold standard for establishing the causality and effectiveness
of an intervention. Many physicians and scientists will not read or consider a clinical trial unless
it is blinded. Blinding describes a process by which information that could skew the results, or
introduce bias, is withheld from either just the participants (“single-blinded”), or both the
participants and experimenters (“double-blinded”).
Including a control group is another way to decrease the bias of the end results. Having half the
subjects receive a sham protocol, the other half actual. A randomized study involves the random
allocation of different interventions (or treatments) to subjects. Randomization ensures that
known and unknown confounding factors are evenly distributed between treatment groups, or the
treatment and control groups.
NON INTERVENTIOANL STUDY
Non-interventional study: To classify a study as non-interventional, it must meet all of The
following criteria:
• Are studies involving products with a marketing authorization that are prescribed in the usual
manner and used in accordance with the authorization?
• When the patient is assigned to a therapeutic strategy within current practice and not
according to a protocol;
• The diagnostic or monitoring procedures are only those ordinarily applied to the therapeutic
strategy;
• Epidemiological methods are used to analyze the data.
PHASES OF CLINICAL TRIALS
Clinical trials involving new drugs are commonly classified into four phases. Each phase of the
drug approval process is treated as a separate clinical trial. The drug-development process will
normally proceed through all four phases over many years. If the drug successfully passes
through Phases I, II, and III, it will usually be approved by the national regulatory authority for
use in the general population. Phase IV are 'post-approval' studies.
Before pharmaceutical companies start clinical trials on a drug, they conduct extensive preclinical studies.
Pre-clinical studies
70 | P a g e
___________________________________________
Research Policies
It involves in vitro (test tube or cell culture) and in vivo (animal) experiments using wideranging doses of the study drug to obtain preliminary efficacy, toxicity and pharmacokinetic
information. Such tests assist pharmaceutical companies to decide whether a drug candidate has
scientific merit for further development as an investigational new drug.
Phase 0
Phase 0 is a recent designation for exploratory, first-in-human trials conducted in accordance
with the United States Food and Drug Administration's (FDA) 2006 Guidance on Exploratory
Investigational New Drug (IND) Studies. Phase 0 trials are also known as human microdosing
studies and are designed to speed up the development of promising drugs or imaging agents by
establishing very early on whether the drug or agent behaves in human subjects as was expected
from preclinical studies. Distinctive features of Phase 0 trials include the administration of single
subtherapeutic doses of the study drug to a small number of subjects (10 to 15) to gather
preliminary data on the agent's pharmacodynamics (what the drug does to the body) and
pharmacokinetics (what the body does to the drugs).
A Phase 0 study gives no data on safety or efficacy, being by definition a dose too low to cause
any therapeutic effect. Drug development companies carry out Phase 0 studies to rank drug
candidates in order to decide which has the best pharmacokinetic parameters in humans to take
forward into further development. They enable go/no-go decisions to be based on relevant
human models instead of relying on sometimes inconsistent animal data.
71 | P a g e
___________________________________________
Research Policies
Phase I
Phase I trials are the first stage of testing in human subjects. Normally, a small (20-100) group of
healthy volunteers will be selected. This phase includes trials designed to assess the safety
(pharmacovigilance), tolerability, pharmacokinetics, and pharmacodynamics of a drug. These
trials are often conducted in an inpatient clinic, where the subject can be observed by full-time
staff. The subject who receives the drug is usually observed until several half-lives of the drug
have passed. Phase I trials also normally include dose-ranging, also called dose escalation,
studies so that the appropriate dose for therapeutic use can be found. The tested range of doses
will usually be a fraction of the dose that causes harm in animal testing. Phase I trials most often
include healthy volunteers. However, there are some circumstances when real patients are used,
such as patients who have terminal cancer or HIV and lack other treatment options. "The reason
for conducting the trial is to discover the point at which a compound is too poisonous to
administer." Volunteers are paid an inconvenience fee for their time spent in the volunteer
centre.
There are different kinds of Phase I trials:
SAD
Single Ascending Dose studies are those in which small groups of subjects are given a single
dose of the drug while they are observed and tested for a period of time. If they do not exhibit
any adverse side effects, and the pharmacokinetic data is roughly in line with predicted safe
values, the dose is escalated, and a new group of subjects is then given a higher dose. This is
continued until pre-calculated pharmacokinetic safety levels are reached, or intolerable side
effects start showing up (at which point the drug is said to have reached the Maximum tolerated
dose (MTD).
MAD
Multiple Ascending Dose studies are conducted to better understand the pharmacokinetics &
pharmacodynamics of multiple doses of the drug. In these studies, a group of patients receives
multiple low doses of the drug, while samples (of blood and other fluids) are collected at various
time points and analyzed to understand how the drug is processed within the body. The dose is
subsequently escalated for further groups, up to a predetermined level.
Food effect
A short trial designed to investigate any differences in absorption of the drug by the body, caused
by eating before the drug is given. These studies are usually run as a crossover study, with
volunteers being given two identical doses of the drug on different occasions; one while fasted,
and one after being fed.
Phase II
72 | P a g e
___________________________________________
Research Policies
Once the initial safety of the study drug has been confirmed in Phase I trials, Phase II trials are
performed on larger groups (20-300) and are designed to assess how well the drug works, as well
as to continue Phase I safety assessments in a larger group of volunteers and patients. When the
development process for a new drug fails, this usually occurs during Phase II trials when the
drug is discovered not to work as planned, or to have toxic effects.
Phase II studies are sometimes divided into Phase IIA and Phase IIB.
•
Phase IIA is specifically designed to assess dosing requirements (how much drug should
be given).
•
Phase IIB is specifically designed to study efficacy (how well the drug works at the
prescribed dose(s)
Some trials combine Phase I and Phase II, and test both efficacy and toxicity.
Trial design
Some Phase II trials are designed as case series, demonstrating a drug's safety and activity in a
selected group of patients. Other Phase II trials are designed as randomized clinical trials, where
some patients receive the drug/device and others receive placebo/standard treatment.
Randomized Phase II trials have far fewer patients than randomized Phase III trials.
Phase III
Phase III studies are randomized controlled multicenter trials on large patient groups (300–3,000
or more depending upon the disease/medical condition studied) and are aimed at being the
definitive assessment of how effective the drug is, in comparison with current 'gold standard'
treatment. Because of their size and comparatively long duration, Phase III trials are the most
expensive, time-consuming and difficult trials to design and run, especially in therapies for
chronic medical conditions.
It is common practice that certain Phase III trials will continue while the regulatory submission is
pending at the appropriate regulatory agency. This allows patients to continue to receive possibly
lifesaving drugs until the drug can be obtained by purchase. Other reasons for performing trials
at this stage include attempts by the sponsor at "label expansion" (to show the drug works for
additional types of patients/diseases beyond the original use for which the drug was approved for
marketing), to obtain additional safety data, or to support marketing claims for the drug. Studies
in this phase are by some companies categorized as "Phase IIIB studies."
While not required in all cases, it is typically expected that there be at least two successful Phase
III trials, demonstrating a drug's safety and efficacy, in order to obtain approval from the
appropriate regulatory agencies such as FDA (USA), or the EMA (European Union), for
example.
73 | P a g e
___________________________________________
Research Policies
Once a drug has proved satisfactory after Phase III trials, the trial results are usually combined
into a large document containing a comprehensive description of the methods and results of
human and animal studies, manufacturing procedures, formulation details, and shelf life. This
collection of information makes up the "regulatory submission" that is provided for review to the
appropriate regulatory authorities in different countries. They will review the submission, and, it
is hoped, give the sponsor approval to market the drug.
Most drugs undergoing Phase III clinical trials can be marketed under FDA norms with proper
recommendations and guidelines, but in case of any adverse effects being reported anywhere, the
drugs need to be recalled immediately from the market. While most pharmaceutical companies
refrain from this practice, it is not abnormal to see many drugs undergoing Phase III clinical
trials in the market.
Phase IV
Phase IV trial is also known as Post-Marketing Surveillance Trial. Phase IV trials involve the
safety surveillance (Pharmacovigilance) and ongoing technical support of a drug after it receives
permission to be sold. Phase IV studies may be required by regulatory authorities or may be
undertaken by the sponsoring company for competitive (finding a new market for the drug) or
other reasons (for example, the drug may not have been tested for interactions with other drugs,
or on certain population groups such as pregnant women, who are unlikely to subject themselves
to trials). The safety surveillance is designed to detect any rare or long-term adverse effects over
a much larger patient population and longer time period than was possible during the Phase I-III
clinical trials. Harmful effects discovered by Phase IV trials may result in a drug being no longer
sold, or restricted to certain uses
DESIGNING A RESEARCH PROJECT
For those with limited to no research experience, designing a research project may seem like the
most daunting of all the tasks involved. Seeking guidance from your mentor and people with
research experience early in this process is paramount. Where to begin? How do you get to the
end? What falls in between? Attacking the research design in a systematic fashion will help
clarify the whole process.
What is the question? Why is it significant? What will you measure to support your hypothesis?
Who will participate? How many participants will you need? How will the data be analyzed?
The answers to these questions form an outline for your research project, and need to be included
in your proposal. Once the proposal is written, the process that ensues will be much clearer.
Parts of a study design include:
• Hypothesis
• Background
74 | P a g e
___________________________________________
Research Policies
• Methods
And The Question Is…
First off, what interests you? This project will encompass many hours over the next two to three
years, so you don’t want to become sick of it. Rather, try to find something you are passionate
about.
The objective of the study is encompassed by the hypothesis.. The hypothesis is based on a
theory you are trying to prove or disprove. Brainstorm questions that need to be answered to
support the study hypothesis. How feasible is it to measure or obtain data about these questions?
What is the significance of your hypothesis? How will society benefit from your research? Will
it act as a stepping stone for other projects? Will your question be able to be reproduced or
replicated? What is the relevance to medical society, pathophysiology and current treatment
regimens?
Have other studies been done that had hypotheses similar to yours? If so, what were their
strengths and weaknesses? Did they leave questions unanswered, or do you want to challenge
the outcomes? This information may be included in the introduction or background section of
the proposal write-up, but it also plays an important role in helping to form the question you will
be investigating.
Background
This is where performing a literature review starts to pay off. This section helps to support the
theory behind the hypothesis. Include prior studies and relevant outcomes. Include
pathopysiology or anatomical correlates. The BACKGROUND sets the stage and will help illicit
support for the hypothesis.
Methods - What/How To Measure
Now that a question exists, outcomes and how they will be measured need to be selected. If your
question is, “What effect does osteopathic manipulation have on the management of knee
osteoarthritis?” you need to establish some outcome to measure – daily pain scale, quality of life,
amount of medication taken. All are examples of outcome variables. How you measure
outcome variables depends on whether you are assessing a dichotomous or a continuous
relationship.
A dichotomous variable is one for which there are only two possible outcomes.
Dichotomous would mean, yes, there was less daily pain on visual analogue scale, or no, there
was not less pain on visual analogue scale, OR less amount of medication taken over a seven-day
period versus no decrease in medication over a seven-day period. A dichotomous variable does
not address the amount of decrease on pain scale or amount of medication taken, just whether
there was a change. Dichotomous variables (absolutes such as “Was daily pain decreased?
75 | P a g e
___________________________________________
Research Policies
Yes/No”) provide less information and require a larger sample sizes. Data will be analyzed by a
chi- squared test.
Continuous outcome variables are measured via a t-test. They can achieve a greater power with
a smaller sample size when compared to dichotomous data.
Predictor and outcome variables can be classified into quantitative or categorical variables (1).
A quantifiable variable is: 1) continuous, quantified on an infinite scale or 2) ordered discrete,
quantified on a finite scale. Categorical variables are classified into categories. If there are only
two categories, such as: dead or alive, then this is termed “dichotomous” category. If there are
more than two categories this is termed “polychotomous” and is further divided into nominal,
such as blood type, and ordinal, such as degree of pain. When designing your study, variable
types help determine how much power your results will have and the efficiency in obtaining
those results. Continuous variables typically give you more “bang for your buck” – more power
with a smaller sample size because they offer more information.
Methods - subject participation – who, where, how long?
This section will tackle sample size first. Sample size calculation is quite important, because too
little and the data will lack power, and too large and your study is inefficient. There does come a
point where after a certain sample size, the increase in the power to support the study is no
longer significant and more work will be done than gains received.
Do This In The Preliminary Design Phase
Who?
Deciding how you will select or recruit for the study’s sampling population is of great
importance. Limiting bias is of course a major factor. Accessing data bases at hospitals, medical
offices, public health agencies or relying on other physicians for referrals are all viable options.
A captured audience, i.e. nursing home or hospitalized patients offer easy access, though may
result in poor follow-up if the study is for an extended period of time and obtaining consent may
be more difficult. Of course, a study that is blinded (single or double) has greater strength.
Exclusion/Inclusion criteria should be consistent with other published studies. This will allow
for greater ease of comparing the studies for outcome efficacy at a later date. Also, keep in mind
who you want to generalize the study to. This takes you back to the question phase, i.e. what is
the significance of the study, who will be effected by the results, how will the results contribute
to our medical understanding or public health policy? The more exclusion criteria involved, the
less the study will be generalized.
Where?
Where will your project take place? How easy is it to get to? If at a hospital or nursing home,
you will need to obtain permission from that particular facility. Obtaining permission in writing
is necessary for your IRB application.
How long?
You need to figure out how long participants will be committed to the project. The longer a
76 | P a g e
___________________________________________
Research Policies
project extends, the more likely it is that participants will drop out you need to keep in mind the
goal of completing the project. If you are conducting an experimental trial, that
translates to 12 months to recruit or obtain participants, conduct study protocol, collect data,
have the data analyzed and complete your paper. If you are performing a prospective study
measuring outcomes yet to occur, keeping the 12-month time crunch is important as well.
Methods - Data Analysis
This is where all your hard work pays off. Unless you have experience in this arena, finding
someone to assist you will be so very helpful.
Contact the Biostatistician at the Research center early in your design phase to obtain sample
size calculation and to discuss the best way to analyze your prospective data.
You also need to have a plan as to how or where you will keep the collected data. It is important
to ensure patient confidentiality. Their intake info should be kept in a locked cabinet.
You will want to design some sort of computerized data base for electronic storage of the
collected information
77 | P a g e
___________________________________________
Research Policies
DETAILED INSTRUCTIONS FOR PREPARING
RESEARCH PROPOSAL
Please submit ORIGINAL COPY, & email a copy to [email protected]
Cover Page. Please complete all details in the forms provided.
Abstract of Proposed Research. Briefly and clearly outline objective, methods and
significance of study. (Recommended length – 200 words)
Purpose of Proposed Investigation and Its Significance. A brief description of the immediate
and long term goals and purpose of the research, and its significance to human health in general,
and to health problems in the Kingdom of Saudi Arabia in particular. (maximum 1 page)
Background Information:
a) Relevant information about the disease (maximum 2 pages)
b) Current status of research on this problem, including literature review (maximum 3 pages)
c) Any previous work done by the investigator (maximum 1 page)
Methods. This is a very important section for a proper evaluation of the scientific merit and
feasibility of the proposal. Please include adequate and concise information on the items listed
below. (maximum 4 pages)
a)
b)
c)
d)
e)
f)
For clinical studies
Patient selection and exclusion criteria
Methods and procedures of the study, treatment schedule, safety precautions
Pre-treatment evaluation
Evaluation during and after study
Criteria for removal from study
Attach Flow sheet and data gathering forms
For Laboratory Studies
a) Experimental plan and design
b) Analytical and other methods to be used
Statistical Methods
a) State number of patients or experiments required
b) End point of Study
c) Method of Analysis
References to be listed: In addition please select a set of the most relevant references to your
research and make it available to the RC members. The principal investigator should submit the
reference package to the library. A file title “Research File” is designated for this purpose.
78 | P a g e
___________________________________________
Research Policies
Budget: If financial support is required, the following should be provided:
a) Detailed budget (see attached form)
b) Justify request. Explain requirement for personnel and time required. If personnel on site,
approval of supervisor.
Facilities to be used: State whether facilities are available and what additional facilities are
required. (maximum one page)
Work Plan: The work plan should clearly state, in graphic term if necessary, the sequence of
major events during the progress of the research. This should include a projected time frame and
utilization of personnel and support, and the methods to be used for monitoring and evaluating
the progress of this project. (maximum one page)
Organization and Management: The plan should clearly state the organization structure and
the role and responsibilities of the key personnel and the methods of supervision. (Maximum one
page)
Informed Consent Form: Attach copy of consent form to be translated into Arabic on
approval**
Departmental Approval: Approval of all Section head/Chairman of the concerned personnel
and facilities involved (see attached form)
Potential Hazards and Toxicity: Fill up attached form.
Curriculum Vitae: (including publications) of Principal Investigators and Co-Investigators
should be attached. Complete the “Investigator Personal Data Form” or attach signed and
dated C.V
** The IRB/ Ethics Committee must approve Informed Consent Form.
79 | P a g e
___________________________________________
Research Policies
9- REFERENCES
1. Ahmed SM, Maurana CA, Engle J, Uddin DE, Glaus KD. A method for assigning
authorship in multi-authored publications. Fam Med. 1997; 29(1): 42-4
2. American Psychological Association. 4th ed, 1994. Publication Manual of the American
Psychological Association. Washington, DC: APA
3. Bhopal R, Rankin J, McColl E, Thomas L, Kaner E, Stacy R, Pearson P et al. The vexed
question of authorship: views of researchers in a British medical faculty. BMJ. 1997; 314:
1009-012
4. Digiusto E. Equity in authorship: A strategy for assigning credit when publishing. Soc
Sci Med. 1994; 38(1): 55-8
5. Erlen JA, Siminoff LA, Sereika SM, Sutton LB. Multiple authorship: Issues and
recommendations. J Professional Nursing. 1997; 13(4): 262-70
6. Huth EJ. Guidelines on authorship of medical papers. Ann Intern Med. 1986; 104: 269-74
7. International Committee of Medical Journal Editors. Guidelines on authorship. BMJ.
1985; 291: 722
8. King CR, McGuire DB, Longman AJ, Carroll-Johnson MR. Peer review, authorship,
ethics, and conflict of interest. J Nursing Scholarship. 1997; 29(2): 163-7
9. Mowatt G, Shirran L, Grimshaw JM, Rennie D, Flanagin A, Yank V, MacLennan,G et al.
Prevalence of Honorary and Ghost Authorship in Cochrane Reviews. JAMA.
2002;287:2769-71
10. Nehring WM, Durham JD. Multiple authorship in nursing. Nurse Educator. 1986; 11(1):
15-8
11. Smith R. Authorship: time for a paradigm shift? BMJ. 1997; 314: 992
12. Yank V, Rennie D. Disclosure of researcher contributions: A study of original research
articles in The Lancet. Ann Intern Med. 1999: 130: 661-70
13. http://www.upenn.edu/grad/authorpolicy_alpha.html
Accessed on December 15, 2005. Contains elaborate information on authorship
guidelines for faculty members and students at the University of Pennsylvania, USA.
14. http://www.mcgill.ca/research-policies/sponsored/policies/ethics/
Accessed on December 15, 2005. Contains research policies and ethics (including
authorship guidelines) outlined by McGill University, Canada.
15. The Belmont Report: The National Commission for the Protection of Human Subjects of
Biomedical and Behavioral Research, April 18, 1979
16. The Nuremberg code. Trials of War Criminals before the Nuremberg Military Tribunals
under Control Council Law No. 10, Vol. 2, pp. 181-182. Washington, D.C.: U.S.
Government Printing Office, 1949
17. WMA Declaration of Helsinki - Ethical Principles for Medical Research Involving Human
Subjects. (http://www.wma.net/en/30publications/10policies/b3/) accessed on May 1st, 2011.
18. Australian code of practice for the care and use of animals for scientific purposes,
National Health and research Council, Australia. 7th edition, 2004
80 | P a g e