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Global Oncology Trials:
Planning For Success
This paper explores several of the upfront areas critical to
the success of global oncology trials, including study planning,
conducting feasibility and navigating regulatory submissions.
A Novella Clinical White Paper
Moving Potential. Forward.
Oncology Clinical
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Oncology
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Global Oncology Trials: Planning For Success
Global Oncology Trials: Planning For Success
Many pharmaceutical, biotechnology and medical device companies have adopted
globalization as a business model for their clinical trials. This model is especially pertinent
within oncology with the number of competing trials consistently rising while patient access
across North America and Western Europe has plateaued. Globalization has enabled access
to appropriate patient populations, which is particularly important given the pipeline
for oncology far out numbers that of other priority disease areas as designated by the
World Health Organization (WHO), surpassing
500 products.i While this geographic diversity of
oncology trial sites has potential to open future
markets, it also adds logistical hurdles ranging from
import and export licenses to regulatory approval to
variances in standard of care.
Strategic, detailed planning between a sponsor
and a clinical research organization (CRO) that
maps out each study step, especially for the first
... geographic diversity of oncology
trial sites has potential to open
future markets, it also adds
logistical hurdles ranging from
import and export licenses to
regulatory approval to variances
in standard of care.
six months or year, can turn cross-border barriers
into collaborative checkpoints along a global cancer
trial’s journey to completion. When a sponsor works with an experienced international
oncology CRO, such as Novella Clinical, to develop a comprehensive set of study plans
and step-by-step processes, regional issues are proactively addressed before the first
patient is even enrolled. On-the-ground knowledge, acquired via an oncology CRO’s daily
experience working with local regulatory agencies, local labs, logistic experts, study sites
and investigators, is critical to a global cancer trial’s success. This paper explores several of
the upfront areas critical to the success of global oncology trials, including study planning,
conducting feasibility and navigating regulatory submissions.
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The World is My Trial Site
The clinical trial landscape has never been more vast and it’s still expanding. Nearly 28,000
principal investigators participated in clinical trials globally during 2012, according to the
Tufts Center for the Study of Drug Development.ii The United States is a location for less than
half of the more than 145,076 trials registered on Clinicaltrials.gov.iii Of note, clinical trials in
China, India and Eastern Europe conducted by Food and Drug Administration (FDA)-regulated
investigators have steadily increased in the last decade, particularly for confirmatory, later
stage clinical trials, Tufts reports.
When narrowed to trials focused on cancer, the scope and scale of clinical research remains
striking. Clinicaltrials.gov lists 38,520 cancer trials, of which 22,723 have a U.S. location and
9,396, European locations, yet Africa (513) and Central America (456) also are active as cancer
trials sites.iv
This geographic diversity speaks to the robust oncology research community’s shared goal of
developing new standards of care for patients with cancer, getting those treatments to patients
sooner and to industry’s need to decrease costs in the face of increased competition for
appropriate patient populations. Yet, the conduct of such research can be as varied as the
many forms of cancer, especially when a trial spans borders.
This paper explores the critical activities to be undertaken during the first six to 12 months of
a trial. Such actions will result in well-run studies yielding the best possible data to determine
if a candidate therapy should come to market and become a part of standard oncology care.
Developing Comprehensive Operational Study Plans
A clinical trial protocol and study plans are the foundations by
which the research goal can be realized. The trial protocol explains
the study rationale, the number and criteria of eligible participants,
the procedures and medications required, and an associated schedule
of assessments.v In contrast, the study plans specify how the trial’s
operational aspects unfold for all involved parties, from the sponsor
and CRO, to central laboratories and vendors, and in some cases to
investigational sites.
Having comprehensive
study plans on a trial will
ensure all team members,
globally, understand
their function and how
to address unforeseen
issues that may arise.
A set of strategic, detailed clinical study plans that accounts and
assigns responsibilities for the regulation and operationalization of each task is essential. The
overarching goal of study plans, particularly for a large global trial, are to ensure every person
involved consistently follows the same instructions and procedures so the resulting data are
valid for analyses and regulatory submissions, regardless of whether the patients are in India
or Ireland. Plans are also the basis for staff training, measurement of trial progress and
quality, and a path for issue escalation when trial or site issues occur.
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Organizing to Prioritize
Study plans often are organized by functional area such as regulatory, clinical monitoring and
data management, even though many plans will overlap functional activities. For example,
clinical monitoring and data management plans both include data cleaning responsibilities.
The best practice is to prioritize plan completion in
alignment with clinical trial process. Plans that
Study Planning
affect study start-up, such as regulatory plans, should
be completed first — before addressing plans that
impact a trial’s readout phase, such as the statistical
analysis plan.
Study plans clearly define the expectations
sponsors and CROs share about the trial’s
performance at the functional and operational
levels. To that end, plans should always
include:
All plans should address requirements such as staffing,
• Project Management & Communication training, documentation and compliance. For example,
• Vendor Management does the plan describe the responsibility for and is
• Clinical Monitoring adequate time allocated to create electronic data
• Regulatory Document Management capture or interactive voice response systems when
• Safety Management different native languages are involved? Or as an-
• Data Management other example, does the plan address global varia-
• Statistical Analysis tions in imaging methods and account for differences
in radiologist training? This is certainly crucial to
any global oncology trial that looks at target lesions,
responses, and progression as part of its major endpoints, especially in light of recent trends to leverage
surrogate endpoints in lieu of overall survival for registration. A comprehensive plan will drive prioritization and allocation of resources, either directly from
the sponsor or via a CRO or other vendors. Ideally,
a sponsor and a CRO would agree and sign off on all
parts of a study plan — functions, resources, timing,
sites — before a study begins.
Other plans that may be very useful to have
for a trial include:
• Medical Monitoring • Unblinded Clinical Monitoring • Integrated Data Review • Patient Transfer • Randomization & Unblinding • Clinical Unblinding • Risk Management • Cohort Management • Patient Recruitment By documenting operational procedures, the study
Project-specific work practices may also
benefit from plans and include:
plans act as a guide for anyone involved, providing
• Filing
clarity on how the study is conducted. Having com-
• Site Activation
prehensive study plans on a trial will ensure all team
• ICF/CTA Reconciliation
members, globally, understand their function and
• EDC Training
how to address unforeseen issues that may arise.
They may even be provided to auditors seeking
information on how various issues were handled.
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Robust Feasibility: Standards, Sites and Care
Performing clinical trial feasibility is one of the initial and most important steps in conducting
a global clinical trial. Feasibility can help determine the best mix of countries and sites, each
of which have their own challenges that could influence the completion of a study.vi A robust
feasibility ensures a realistic assessment of the capability of each region, country, and potential
trial site to conduct the trial and will ultimately influence study site selection. Feasibility must
also address provision of the standard of care for trial participants, where the trial stands in
the overall competitive landscape, and the ability to obtain and distribute the medicines or
devices involved in the study.
Evaluating National Standards
Because standards of care, comparator medicines access, and diagnostic testing capabilities
— among other trial components — will vary from nation to nation, all late-phase protocols
should be evaluated for regional- and country-specific feasibility. Depending on the trial size
and indication, a CRO well versed in conducting feasibility can assist a sponsor in providing
large-scale feasibility or a more targeted effort.
Large-scale feasibility is appropriate for oncology studies anticipated to run in more than 10 countries
and more than 100 sites in relatively common indications, such as non-small cell lung cancer or
prostate cancer. This approach is typically a site survey coupled with regional key opinion leader
feedback, which yields country-level input as well as global feasibility for the trial.
Conversely, targeted feasibility may be appropriate for smaller scale studies in relatively rare
indications, such as leiomyosarcoma or gastric cancer, or with an unusually complex investigational product. This approach favors one-on-one physician communication to gauge site-specific
interest and challenges, as these issues can be magnified in a smaller trial.
Regardless of the approach, the questions being asked are critical to the depth of the feasibility
and to ultimately seeing a trial come to fruition in a given country. The CRO involved must
have the oncology experience and global expertise to ask the right questions, for example:
• Will this protocol align or compete with the typical patient treatment pathway in this
country in this indication, inclusive of newly approved therapies and off-label use of others?
• Is the mechanism of action of the investigational product compelling, and how will this
drug be viewed locally versus other competing trial options?
• Is the required diagnostic test approved and available at all sites or will the sites be able
to ship tissue samples abroad for diagnostic analysis?
• Will the local Competent Authority or Ethics Committee (EC) find use of additional
diagnostics, such as MRI scans, acceptable?
• Must the comparator drug be provided or may this be reimbursed?
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The ultimate goal of feasibility conduct is to provide a report to the sponsor that outlines the
likelihood of successful patient recruitment and study completion in any given country, along
with potential issues for the trial as a whole as well as at a regional, country or local level. A
robust feasibility will help reduce start-up time and resources as well as the enrollment period
because it anticipates and addresses all of the regulatory and clinical hurdles, thus ensuring
fewer approval and site issues and smoother trial progression.
A sponsor, with the help of a CRO, can use the feasibility analysis to adjust the protocol or trial
plans to allow for regional variances. For example, a sponsor may dictate a specific number
of cycles for adjuvant oncology therapy in the protocol, but advanced feasibility may indicate
this cycle number is only standard in some regions and could lead a sponsor to relax criteria
for minimum and maximum numbers of cycles. As another
example, feasibility results may help sponsors identify and
incorporate the methods necessary to address potential
differences in protocol interpretation by region. Recently,
protocol deviations were tied to a 75 percent increase in the
risk of treatment failure and overall mortality in an analysis
of radiation oncology studies. The investigators found in their
review of quality assurance data from eight clinical trials,
together addressing seven cancer types, protocol deviations
A robust feasibility will
help reduce start-up
time and resources as
well as the enrollment
period ...
ranged from 8 to 71 percent, and were associated with
significant decreases in overall survival (P < .001) and increased risk of treatment failure (P = .009).vii Obviously, an ability to identify and address areas
of the protocol that can lead to substantial variation in treatment by country, and thus the ultimate
outcome of the trial, points to the significant value of a thorough feasibility in the early trial
planning stages.
Selecting Sites
Ideally, a sponsor chooses sites based on the prevalence of the type of cancer targeted by the
investigational therapy and access to those patient populations combined with the on-theground feasibility results. Sponsors also consider the caliber and capabilities of the clinical
research institutions and investigators that care for these patients.
Sponsors may also select sites based on the potential future markets for the candidate drug
should it prove safe and effective in trials and receive regulatory approval. A known benefit
of large oncology global trials is that they enable investigators, regulators and patients to
become familiar with the sponsor and the candidate therapy long before marketing approval
submissions occur.
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Also, having opinion leaders in each region or country provide a review of the draft protocol
aids in site selection, timely regulatory approval of the trial and, ultimately, study success. The
comments from such experts on the study’s scientific design, patient population, standards
of care, and familiarity with and tolerance of an investigational product or approach can help
refine a protocol to ensure that sites and regulators in that region find the trial acceptable.
For sponsors for whom the trial is the beginning of an investigator or
institutional relationship, an experienced CRO can offer guidance in
assessing the study feasibility and directing the sponsor to like-minded
key opinion leaders who are effective at study implementation.
After all such criteria are compiled and considered, some sponsors
may anticipate that selection means a review of all eligible sites. Such
a comprehensive approach in a global trial, with well more than 100
sites, is costly and is not typically necessary. Rather, Novella Clinical
recommends sponsors establish minimum requirements for sites, perhaps
using a scoring system, so as to efficiently eliminate low-ranking sites
from consideration. Factors with representative weights can be used
in the scoring such as monthly patient volume in the specific oncology
... having opinion
leaders in each region
or country provide a
review of the draft
protocol aids in site
selection, timely
regulatory approval of
the trial and, ultimately,
study success.
niche pursued by the protocol, or perceived screen failure rate as
dictated by the inclusion/exclusion criteria or specific biomarkers
pursued. A CRO with a long working history in oncology and with cancer sites globally can
add value by leveraging proprietary data on historical site performance on past trials inclusive
of time to open, enrollment, and data quality. All of this can help focus the site selection effort
to hone in on the sites with the potential to work best for that particular trial.
Covering the Cost of Care
Standards of cancer patient care differ by country and even from site to site. For example,
while the patient’s stage of cancer at diagnosis is a significant factor in the selection of care,
so are treatment availability and costs as well as health care professionals’ knowledge of and
skill with those treatments. The consequences are apparent in the wide variety in patient
survival rates.viii A 2009 study found five-year survival rates for breast cancer patients ranged
from about 84 percent in the U.S. to 39 percent in Algeria.ix
These same factors have implications for large global oncology trials. Novella Clinical
recommends sponsors establish how standards of care will be upheld and paid for, including
reimbursement, as early as possible in the trial planning period because of the potential for
significant budget impact.
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While sponsors provide participants the candidate medicine at no charge, the reimbursement
costs and policies for comparator drugs or concomitant therapies related to a patient’s condition
change with the trial site. For example, if the investigational drug is added to a standard treatment
regimen, how will the cost of the standard treatment be covered — through insurance,
governmental support or paid for by the sponsor?
Often, a sponsor may select a comparator medicine such as a chemotherapy because it is a
reimbursed standard in the U.S. However, the drug may not be available in China or is available
but must be reimbursed in Eastern Europe. In fact, Novella Clinical has found some hospitals
and EC request sponsors not only pay for the comparator drug for the duration of the trial, but
also for as long as the patient needs it before another treatment is available. Obviously, this
reimbursement component can result in a substantial cost burden on the sponsor. This financial
aspect could ultimately influence the decision of whether to run a trial in a particular country,
thus highlighting the importance of early identification of such local factors.
Procuring Drugs
Nearly 60 percent of biopharmaceutical companies conducting emerging market-based trials
report shipping and logistical support are significant challenges to their trials.x Many sponsors
may try to handle such negotiations directly, but a CRO can be of great assistance, especially on
the scale of a global trial.
For drug procurement, a CRO can have an advantage over a sponsor in that they can apply their
expertise in running trials as well as their independent status to act as a broker to achieve
optimal pricing and efficient supply chains for medicines needed for the trial. A CRO is
particularly well suited to manage the logistics of meeting customs regulations for drug
importation into each country in the trial.
Getting Real about Regulations
Despite the existing guidance and the common goals of conducting ethical, rigorous clinical
trials, the process for authorization to conduct international clinical trials is as varied as the
geographies in which they take place.
For each study site under consideration in a large global trial, the approval process layers can
be overwhelming for an experienced sponsor, let alone one embarking on its first international
study. Each country has a national agency for clinical trial protocol authorization, each with
particular processes and procedural requirements for document preparation, submission,
review and approval. Moreover, despite national standards, some countries also impose everchanging regional and local requirements, in addition to individual site Institutional Review
Board (IRB) and EC reviews, as well as varied requirements on the timing and status of budget
negotiations and contracts. Additionally, in Europe, all investigational medical product (IMP)
trials must receive an EU Drug Regulating Authorities Clinical Trials (EudraCT) number,
issued by the European Medicines Agency.xi
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Voluntary Harmonization Procedure
The EU clinical trials directive 2001/20 EC addresses good clinical practice in the conduct of
clinical trials on medicinal products for human use. In April 2009, the EU Heads of Medicines
Agency’s Clinical Trials Facilitation Group launched the Voluntary Harmonization Procedure (VHP)
as part of this directive. VHP allows sponsors of EU multi-national clinical trials to obtain a harmonized assessment of their Clinical Trial Authorization application by all the National Competent
Authorities (NCAs) of all of the EU member countries involved. Via the VHP, a sponsor submits a
single set of core documents electronically to the VHP coordinator. Following fixed timelines, the
NCAs simultaneously and in a coordinated manner then assess the documents. After the assessment,
a sponsor receives a single, harmonized set of questions that stem from the scientific discussion
between the Lead Member State and the other Member States involved in the assessment.
A 2011 report documented that from March 2009 until November 2011, 97 applications were received,
comprised of 86 standard and 11 accelerated, which stemmed from the pandemic influenza vaccines.
Some 55 different sponsors applied for VHP, the majority of which came from the U.S., Germany,
France, the United Kingdom, Belgium and Switzerland. The average number of member states
selected and participating in particular VHP assessments is six, but have ranged from two to 14.
Of the 22 countries participating, Germany, France and Spain were the most active.
Another authorization influencer may not readily be apparent to some sponsors: the competitive environment. Because of the dynamic nature of oncology research, countries will differ
on the evolution of their standard medical practices. This diversity means that across borders,
regulatory authorities will possess different levels of in-house expertise with treatments that
might be comparators or competitors to a sponsor’s investigational product. Having a precedent
drug for specific countries as a reference point in a regulatory submission can be helpful to
authorization.
Additionally, sponsors should consider the role of local key opinion leaders who may be consulted
by reviewing authorities. Such experts might be approached by sponsors to review a draft
study protocol or help in the identification and recruitment of local investigators, affording
these leaders more familiarity with the details of the trial, which then enables them to provide
more informed opinions to reviewers.
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Considering the Clock
An experienced CRO can shepherd sponsors through the myriad of approval processes because
the team already knows the required steps and documentation for each trial venue, as well as
current issues or likely questions for particular reviewers. Among the topics for guidance a CRO
should offer sponsors is estimating the actual time it takes to achieve authorization for trials
to commence, inclusive of all country / local approvals, contracts, and site activation / IP release, as well as understanding the meaning and implications of review responses. With such
counsel, a sponsor can proactively prepare tailored submission documentation, which creates
trial efficiencies downstream.
Many country-level agencies have well documented timelines
and processes for regulatory review; however, these can still
vary significantly, leading to large delays in regulatory authorizations. Novella Clinical’s experience has repeatedly shown
the agencies in countries such as the U.S., Belgium, the U.K.
and the Netherlands have fairly quick and efficient processes,
while others such as India, China or Brazil have variable
timelines largely dependent on individual reviewers. In some
South American countries and certainly in China, country-level
approval timelines may grow to nine to twelve months; these
slower review timelines can obviously impact trial activation
and enrollment timing.xii
Many country-level
agencies have well
documented timelines and processes
for regulatory review;
however, these can
still vary significantly,
leading to large
delays in regulatory
authorizations.
A recent, first-of-its-kind analysis of a large phase III breast
cancer trial with 8,300 participants conducted in 44 countries had regulatory approvals ranging
significantly in median time from 236 days in South America to 26 days in North America. The
authors noted country economics played a role in the approval timing, but surprisingly with
upper-middle economies having longer median times to approval, 123 days, than either highor lower-middle income economies, 47 and 57 days, respectively. In contrast, no significant
difference occurred for EC/IRB approval times, which had a median of 59 days across the
studied regions. Similarly, the median times from EC/IRB approvals to first recruited patient
did not differ, tallying 169 days. The long delay in recruiting patients may have occurred
because of the time required to negotiate contracts between the sponsor and sites, delays in
importing the study drug or investigators’ interest in referring patients to the study, the authors
noted.xiii These hurdles are just some of the bottlenecks that affect all global trials, but ones that
an experienced CRO can help mitigate for a sponsor.
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Local approvals must also be considered, as these often must be pursued in parallel or serially
with country or regional reviews. Local approvals will be impacted by site and investigator evaluations, contracts and site initiations, as well as other factors. Sponsors must consider these local
steps in a trial’s overall timeline, as they can significantly add to the time “budget” and are often
the rate limiting step in the overall initiation process. Novella Clinical has a proprietary model for
trial startup and enrollment timelines that begins the day a sponsor says “go,” and includes:
• Feasibility-based enrollment rate assumptions by country
• Full site selection activities
• Approvals at regional, country and local levels, including contracting
• Timed ramping of site initiations by country as many sites open over a range of months
• Average time from site initiation to first patient dosing
• Allowances for regional slow-downs by month due to local cultural nuances
All of this enables us to assist sponsors with the “real world” planning for a trial, providing a
comprehensive view from startup to last patient. Because of the variance in timelines for approvals,
a CRO that understands country-, region- and site-specific requirements can help a sponsor
navigate the concurrent processes necessary to obtain authorization for international trials.
While no timeline is perfect, ones that account for delays, questions and changes, even
holidays, permit realistic planning.
Interpreting Responses
The nature of the review process itself varies by country. Some agencies prefer submission and
no communications, while others, Novella Clinical has found, require much more interaction to
move authorization forward. A CRO with long-standing regulatory relationships can manage such
discussions, answering questions in face-to-face meetings and creating significant timesaving for
sponsors.
Differences in the style of regulatory responses also vary with geography, which for the novice
sponsor can lead to misinterpretations. Some agencies, like those based in Eastern Europe,
are extremely succinct when responding. In such instances, Novella Clinical has found that
while a written response may be a simple no, speaking with the staff reveals what criteria and
decisions led to that conclusion, thus providing a roadmap to a sponsor for the modifications
necessary for approval.
Accounting for Treatment Complexities
Documenting and describing all of a trial’s treatments, not just the investigational drug or device,
adds complexity to requesting regulatory authorization of a study. The type, number and
combination of study treatments that a patient might receive and their previous regulatory
approvals or marketing authorizations must be considered. Additionally, the sourcing and
classification of treatments must be carefully accounted for as part of the regulatory submissions.
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Authorizing organizations require information regarding the chemistry, manufacturing and
controls (CMC) of the drug substance and the drug product to assure the proper identification,
quality, purity and strength of the investigational drug.xiv The detail required in CMC documentation will vary, however, with the trial’s phase, size and duration as well as the quality, control and
manufacturing of the treatment.xv These factors might include a drug’s dosage form, delivery,
bioavailability, stability, prior usage and regulatory history, as well as other factors. The goal of
CMC is to demonstrate the identity, quality, purity and strength of the investigational product to
help ensure safety of patients, so documentation in earlier trials focuses on risk, while later trials
also address the relationship of the investigational treatment to a potential marketed product.
Drugs in trials must be made under good manufacturing practice (GMP), but may require special
trial-specific modifications. If a sponsor manipulates a drug in any way for the trial, new
labeling and packaging are necessary. Sponsors who do not adequately address GMP issues
can receive a rejection of their trial by a regulatory authority, which can cause a scramble to
replace an entire country just as a trial is getting underway.xvi
In the EU, regulations require the manufacturer or importer must authorize the medicines, with
a qualified person based in the EU and independent of the sponsor assuming responsibility for
quality assurances. In contrast, sponsors of U.S. trials can assume this responsibility.xvii The FDA
CMC requirements are similar to those found in many European countries, but other global
regions can differ. For example, while Korea parallels the U.S. FDA requirements for CMC
information to be submitted in an IND, China requires a significant amount of CMC information, which can be an issue for products with a complex manufacturing process or for studies
with more than one investigational product. The Chinese State Food and Drug Administration
also requires extremely detailed manufacturing protocols that can enter into what sponsors
consider to be the realm of intellectual property.xvii
GMP drug modifications are not just a
country-specific concern and may also
extend to the institutional pharmacies, if
significant preparation or manipulation
of the product has to occur at a trial site.
Submissions for study protocols that use
drug combinations must consider whether
the treatment as a whole or any of its
As oncology trial sponsors begin testing
more biologics, the regulatory path becomes
more complicated given the greater
complexity of biologics and because many
agencies differ in their review processes for
biologics compared to small molecules.
components are standard. For example,
not all countries use the combination chemotherapy known as CHOP as the standard regimen for treating patients with Non-Hodgkin’s
lymphoma. Similarly, if a protocol requires prior treatment with a specific drug as inclusion criteria,
the drug should be in regular use in the market under consideration. If not, regulatory authorities
are likely to decline the application.
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Moreover, drug classification as a small molecule or biologic matters. As oncology trial sponsors
begin testing more biologics, the regulatory path becomes more complicated given the greater
complexity of biologics and because many agencies differ in their review processes for biologics
compared to small molecules. Unlike many small molecule-based protocols, those using
biologics, especially when examining the complexity imparted by vaccines and gene therapies,
can require additional approvals as well as process and quality control steps and approvals for
shipping, reconstitution, storage and administration.
Ensuring Informed Consent
Informed consent is the process of ethically explaining the trial to a patient so that he or she
can decide whether to participate. Each site’s IRB/EC must approve the appropriate forms to
be used at that site as, on occasion, do the country-level regulatory agencies.
Health literacy and cultural norms play roles in the creation of informed consent forms (ICFs).
These documents contain the trial intent, procedures, potential risks and benefits, as well as other
technical information. Using the same descriptions for investigators, regulators and patients is not
appropriate, as patients must receive the information in words they readily understand.
The “translation” from trial protocol to patient documents has legal, scientific and cultural
considerations, about which a sponsor can seek counsel from a CRO. The CRO can, as needed,
develop the documents into collateral that can be used for patient discussions if relying on
patients’ reading ability is not appropriate. The CRO also can provide language translation
services for the collateral into the site-specific language, including regional dialects if necessary. For example, India has two official languages, but the national government recognizes
more than a dozen. India’s states also recognize even more regional languages, while patients
may communicate in dialects. The result? ICF translations into a minimum of eight to 10
languages.xix
Informed consent is not just about a patient’s participation. Ethically, this process also must
address the number and kind of the patient’s biological samples, the methods of collection,
their immediate and long-term use, and their storage and disposal, so that patients know their
personal privacy is ensured and respected. Sponsors should be transparent about such plans
because regulators may ask and the wait to provide the answers can cause trial approval delays.
Also, as cancer treatments have become more targeted, pre-screening patients for trial eligibility
may require separate consents from those obtained for actual trial enrollment. For example, in
a trial for a drug designed to counter a specific genetic mutation, a patient’s eligibility will be
determined based on a tissue sample, for which informed consent is required.
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On the Horizon
Advances in the harmonization of international clinical research are anticipated to beneficially
impact the scientific and ethical integrity, quality and efficiencies of such investigations.xx
Thought leaders have called on organizations such as the WHO or the Institute of Medicine
to help reach consensus to speed harmonization efforts on trial design and conduct, with
contributions from academia, industry and regulatory agencies as well as from developed
and developing countries.xxi American Society for Clinical Oncology’s International Affairs
Committee also is assessing regulatory issues, burdens and diversities in international cancer
clinical research, and its initial 2011 report documented that low- and middle-income countries
consider the regulatory procedures of competent authorities a significant barrier that should
be optimized.xxii
While these efforts move forward, one noticeable action
toward such harmonization is the 2012 establishment of
TransCelerate BioPharma, a consortium of 10 international
biopharmaceutical companies that aims to improve the
quality and efficiency of clinical trials.xxiii TransCelerate’s initial focus is the execution of clinical trials, which
includes five projects that could have major impacts on
times and costs. These projects include the development
of a shared user interface for investigator site portals,
mutual recognition of study site qualification and training,
approaches and standards for risk-based site monitoring,
clinical data standards, and comparator drug supply
Advances in the
harmonization of
international clinical
research are anticipated
to beneficially impact
the scientific and
ethical integrity, quality
and efficiencies of such
investigations.
modeling.xxiv
The FDA’s Center for Drug Evaluation and Research applauded the TransCelerate initiative,
noting that in the pre-competitive arena, such collective use of experience and resources
has the promise to lead to new paradigms and cost savings in drug development that in turn
would strengthen the development of innovative and much-needed therapies for patients.xxv
More information is available at http://transceleratebiopharmainc.com/. xxvi
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About Novella Clinical
Novella Clinical, a Quintiles company, is a full service clinical research organization specializing
in supporting emerging oncology companies. Headquartered in Research Triangle Park, N.C.,
and Stevenage, UK, Novella is experienced in early, mid- and late-phase oncology trials and
provides the experience and insight to bring cancer medicines to market on time and on
budget. For more information, visit novellaclinical.com/oncology or contact us at 866-303-4966.
You see beyond the clinical trial. Your goal is to
ultimately give people a better quality of life and
more time to enjoy those special little moments.
Novella Clinical is proud to be a part of your mission.
Moving Potential. Forward.
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