* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
Download Ethical Aspects of Research Involving Human Subjects will be
Tuberculosis wikipedia , lookup
Dirofilaria immitis wikipedia , lookup
Trichinosis wikipedia , lookup
Meningococcal disease wikipedia , lookup
Human cytomegalovirus wikipedia , lookup
Onchocerciasis wikipedia , lookup
Chagas disease wikipedia , lookup
Neonatal infection wikipedia , lookup
Microbicides for sexually transmitted diseases wikipedia , lookup
Marburg virus disease wikipedia , lookup
Neglected tropical diseases wikipedia , lookup
Hepatitis C wikipedia , lookup
Leptospirosis wikipedia , lookup
Schistosomiasis wikipedia , lookup
Coccidioidomycosis wikipedia , lookup
Hepatitis B wikipedia , lookup
Hospital-acquired infection wikipedia , lookup
African trypanosomiasis wikipedia , lookup
Sexually transmitted infection wikipedia , lookup
Eradication of infectious diseases wikipedia , lookup
Ethical Aspects of Research Involving Human Subjects- The Challenges of ERC/ IRB in reviewing protocols involving research on highly infectious diseases Prof Elizabeth Anne Bukusi Deputy Director(Research & Training) Kenya Medical Research Institute Recent highly infectious epidemics EBOLA SARS MDR/XDR TB Emerging infections HIV/AIDS HIN9 HINI Concerns High mortality and morbidity Very short timescale for decision making Some are Highly contagious Global susceptibility Threat to global security and economy But some special features A case may also be a risk factor - Person with infection can also be source of infection People may be immune - Having had an infection or disease could result to resistance to an infection (immunity) A case may be a source without being recognized - Asymptomatic/sub-clinical infections There is sometimes a need for urgency - Epidemics may spread fast and require control measures Preventive measures (usually) have a good scientific evidence Challenges in reviewing infectious diseases protocols Infectious Diseases spread quickly, with Infectious Diseases spread quickly, with high mortality, crossing borders/ high mortality, crossing borders Information and expertise may be limited Need to make the correct decision quickly sometimes with little information and time Uncertainty over the safety and effectiveness of the trial productespecially in epidemic situation Chain of Transmission Reservoir Person-toperson transmission Portal of exit Susceptible host Agent Portal of entry Reservoir and source of infection Reservoir of infection Ecological niche where the infectious agent survives and multiplies Person, animal, arthropod, soil, or substance Source Human Animal Environment Transmission routes Direct transmission Indirect transmission Mucous to mucous membrane Waterborne Across placenta Airborne Transplants, blood Foodborne Skin to skin Vectorborne Sneezes, cough Objects/Fomites Possible outcomes after exposure to an infectious agent Exposure No infection Death Clinical infection Immunity Subclinical infection Carriage Carriage Non-immunity Dynamics of disease and infectiousness Latent period Infectious period Incubation period Infection Clinical disease Onset of symptoms Non-infectious period Recovery Resolution of symptoms Time Relationships between time periods Transmission Second patient Latent period Infectious period Incubation period First patient Transmission Latent period Incubation period Infection Clinical disease Infectious period Clinical disease Serial interval or generation time Time Disease occurrence in populations Sporadic Occasional cases occurring at irregular intervals Endemic Continuous occurrence at an expected frequency over a certain period of time and in a certain geographical location Epidemic or outbreak Occurrence in a community or region of cases of an illness with a frequency clearly in excess of normal expectancy Pandemic Epidemic involves several countries or continents, affecting a large population What causes incidence to increase? Reservoir Person-toperson transmission Portal of exit Susceptible host Agent Portal of entry Factors influencing disease transmission Climate change Megacities Pollution Vector proliferation Environment Vector resistance Vectors Animals Food production Infectivity Agent Intensive farming Antibiotics Pathogenicity Virulence Immunogenicity Population growth Migration Behaviour Antigenic stability Reproductive rate • Potential of an infectious disease to spread in a population • Dependent on 4 factors: – Probability of transmission in a contact between an infected individual and a susceptible one – Frequency of contacts in the population contact patterns in a society – – Duration of infectiousness Proportion of the population/contacts that are already immune, not susceptible Basic reproductive rate (R0) Basic formula for the actual value: R0 = β * κ * D β - risk of transmission per contact (i.e. attack rate) Condoms, face masks, hand washing β ↓ κ - average number of contacts per time unit Isolation, closing schools, public campaigns κ ↓ D - duration of infectiousness measured by the same time units as κ Specific for an infectious disease Early diagnosis and treatment, screening, contact tracing D ↓ Ethical issues Vulnerability Confidentiality Beneficence Choice of control Study design Informed consent Standard of care Compensation Oversight and regulation Post trial access Vulnerability Vulnerability Participants from developing countries are especially vulnerable due to their poverty, underdevelopment high disease burden Confidentiality Quarantine – identification may lead to Lack of confidentiality by Invasion of privacy exposure of sensitive personal information Could lead to negative social outcomes like job loss or loss of insurance coverage Confidentiality ERC Role in protection of Confidentiality Ensure subjects are protected from unwarranted and unwanted disclosure. Prohibit disclosures in cases Ensure Identifiable subject information is not disclosed without their consent Limit what information is recorded in subjects medical records to avoid breach of confidentiality This is a against a back drop of community or social concern especially over infectious agents with public health impact. Risk/Benefit Analysis What is the risk in relation to the benefits? What is the risk among subjects most likely to benefit from participating in the trial ? What is the relevance of the trial on the population? Is there compelling need to use the selected Population, will they benefit the most? Benefit vs. Risk ERC considerations: Severity of the disease, risk of infection, and subjects’ vulnerability and potential adverse events and outcomes Evidence that animal and lab tests have demonstrated safety Compelling need to use selected participants Potential benefits of the intervention Benefits, risks Does address how benefits and risk will be shared Did the community have a say on inclusion or exclusion of subjects? Equipoise and choice of control Does the selected control best establishes the value of the candidate intervention and has documented positive outcomes for the condition ? If no effective intervention exists, a placebo may be appropriate, with good informed consent. A licensed and effective intervention is by default the comparator of choice for the control group. Any exception should be fully justified to, and carefully reviewed by, relevant ethics committees ERC community considerations Ensure that the community is well informed before the trial. Justification for segregating and providing differential treatment Understanding of social and cultural practices that may promote or inhibit trial implementation Good community practices not standard and not always well documented Study design Trials should be design to involve those at risk of exposure and those who stand to benefit the most The type of infectious disease, its route of transmission and infectiousness, what is known about it , and any known treatment or support determine the kind of study design that is most appropriate Informed consent The value of informed consent may be diminished in highly infectious diseases due to morbidity. Informed consent Challenges further heightened by social-economic factors e.g. lack of education and poverty in developing countries Voluntary participation / and especially where proxy consent is required Language and translation of concepts may be a challenge Improved medical care provided during trial may constitute inducement Standard of care Should be defined prior to the trial’s initiation through stakeholders consultation and agreement Consensus between ERC’s where North- South collaborations are engaged in approval would be desirable Compensation Reimbursement/compensation should not constitute inducement The local ERC should provide guidance on the appropriate compensation depending on the context of the trial The protocols need to provide indemnity incase of injuries in the course of the trial Local indemnity cover is not easily available Oversight and regulation Clinical trials often involve multiple institutions, which lead to a complex process of ethical and regulatory review The capacity of National and local regulatory and ethical review bodies especially in developing countries should continually improve their processes Study Monitoring/ Audits Monitoring of studies often included in the design – for quality control DSMB included to ensure safety and for clear stopping rule decisions Local ERC review of ongoing SAE – capacity may be a challenge ERC oversight for actual conduct may also be a challenge do to resources For multi site trials, efforts should be made to enable ERCs share information and concerns, and a mechanism by which to resolve difference ERCs must ensure sponsors have provisions for monitoring and maintenance of safety and efficacy records of the intervention Post Trial Access ERCs need to ensure that provision is made for the trial community to benefit from early access to any product of the trial, infrastructure and knowledge brought by the trial Post trial access While the ERCs ensure the protocol includes information to ensure that products which are valuable for treatment/ prevention are not only available but affordable and in the quantities needed to tackle the outbreak at its epicenter. Enforcement of such agreements are challenging – both follow up and implementation The investigators have the burden/ responsibility of follow up No clear mechanisms for research to policy and best practices in a rapid manner except for some with strong advocacy groups. Thank- you Anderson RM & May RM, Infectious Diseases of Humans: Dynamics and Control, 11th ed. 2006 Giesecke J, Modern Infectious Disease Epidemiology, 2nd ed. 2002 Barreto ML, Teixeira MG, Carmo EH. Infectious diseases epidemiology. J Epidemiol Community Health 2006; 60; 192195 Heymann D, Control of Communicable Diseases Manual, 19th ed. 2008 McNeill, WH. Plagues and Peoples, 3rd ed. 1998 Everlyn Ombati , Timothy Kipkoskei and KEMRI SERU team.