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Collection of Real World Data in the Context of Rare
Diseases and Expanded Access Programmes
February 2015
Collection of Real World Data in the Context of Rare
Diseases and Expanded Access Programmes
Introduction
Real-world data (RWD) is generally the term used to refer to any data which is
collected outside of randomised clinical trials (RCT). The data can be from
sources including patient data from hospitals and clinicians. RWD combined
with information from RCTs can provide better research outcomes and
improved healthcare.
Expanded access is a means by which manufacturers make investigational new
drugs available under certain circumstances to treat a patient(s) with a serious
disease or condition who cannot participate in a controlled clinical trial. The
primary intent of expanded access is to provide treatment for a patient’s
disease or condition, rather than to collect data about the study drug. The
data from expanded access programmes falls under RWD as it is outside RCTs.
This document highlights the importance and improvements that can be made
in collecting data from expanded access programmes.
The Importance of Real World Data for the Pharmaceutical Industry
Most human use of investigational new drugs takes place in controlled RCTs
conducted to assess their safety and efficacy. Data from these trials are used
to determine whether a drug is safe and effective, serving as the basis for the
drug marketing application. The environment in which the RCTs are conducted
is idealised and can only measure efficacy in limited populations. They cannot
provide a true indication of the effectiveness of the drug in real-life where:
+ the patient might use other medications that may influence or confound
the effect of the primary drug or;
+ use of the drug by patients who could otherwise be excluded from the
RCT or;
+ use of the drug in different doses or duration which is different from the
RCT.
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RWD can help explain the effectiveness of the drug in the real world setting,
whilst RCTs explain the efficacy of the drug under ideal controlled and
monitored situations.
RWD research spans a wide range of research methodologies and very
different data sources, including:
+
+
+
+
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Patient registries;
Existing electronic health records;
Routinely collected administrative data;
Primary patient level data collection (prospective or retrospective);
Population health surveys.
The use of the RWD depends mainly on the stage of the drug development. If
the drug is at is at pre-approval stage.
Figure 1 – Pre-approval: the data may be used to evaluate unmet clinical
need, describe pathways of care, and collect resource use, for example in
preparing for a health technology assessment as part of the reimbursement
process.
During the post-marketing phase for a medicine, it is used to demonstrate the
value and safety of a medicine in the marketplace in a way that is aligned with
health/regulatory authority’s priorities, patient needs and national agendas.
Expanded access regulation makes promising drugs and devices available to
patients with serious or immediately life-threatening diseases. The patients
given access may not qualify for these controlled trials because of other health
problems, age, or other factors (e.g. a patient may not live sufficiently close to
a clinical trial site).
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Collection of Real World Data in the Context of Rare
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Expanded access is usually given:
+ on a case-by-case basis for an individual patient;
+ for intermediate-size groups of patients with similar treatment needs
who otherwise do not qualify to participate in a clinical trial;
+ for large groups of patients who do not have other treatment options
available (once more is known about the safety and potential
effectiveness of a drug from ongoing or completed clinical trials).
In all of the above cases the primary intent of expanded access is to provide
treatment for a patient’s disease or condition, rather than to collect data about
the study drug. Since these investigational drugs/devices have not yet been
approved by the regulatory bodies and they have not been proven to be safe
and effective there is an opportunity to collect and use the data from the
patients on expanded access to support New Drug Application (NDA).
In the UK in 2011-2012, there were a total 97,089 clinical trial participants
across clinical trials in all phases. In contrast many more expanded access
programmes were initiated to extend quality of life and end of life situations
outside of this highly regulated situation.
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Collection of Real World Data in the Context of Rare
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Figure 1:
Pre-approval
Challenges for Real World Data
Collection of real-life data may differ between health care centres or countries.
Treatment patterns sometimes differ considerably from one country to
another so prospective research must be conducted in a series of countries to
enable a meaningful picture to be presented to the local reimbursement
authorities. This is compounded by the fact that the description of an event
often differs in real-life data compared to a randomized trial (e.g. the severity
of the condition).
Most of the databases are not complete across different health care centres.
Without control of the way the drug is administered there are more sources of
bias and confounding. There is also a greater potential of various sources of
bias that can completely distort the results. One typical example is where
different degrees of severity of a condition are treated with different drugs.
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Collection of Real World Data in the Context of Rare
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In consequence a treatment that is actually more effective may look less
successful in RWD if it is administered to very severe cases only.
In contrast in RCT it is mainly given to patients with mild conditions. Thorough
statistical methods can control parts of these biases; however the risk of
misinterpreting studies without randomized drug allocation remains high.
Opportunity to Improve Collection
For expanded access programmes there is an opportunity to overcome some
of the challenges facing RWD. Data can be collected prospectively and
improvements made on data quality.
Planning of the collection of the data needed for specific analysis can be done
prior to the drug being given to the patients. A company can ensure that the
same collection forms are used by General Practitioners in all practices that
have been given expanded access to use the company’s drug. There are tools
presently available in the public domain that could easily support the collection
and summarising of this data.
With the advent of real-time data collection on enabled and connected devices
such as phones, tablets and computers, cloud-based hosted domains support
real-time reporting. We no longer have to rely on patients to complete
questionnaires as mobile phones and tablets incorporating reminders, will
assist in improving patient compliance. We can engage Physicians by providing
them with the necessary tools that harness the potential of current
technology. These include online edit checks and logic tests as well as
electronic signatures and verification.
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All of these functionalities when incorporated and exploited appropriately can
act as facilitators and enablers, putting patients back at the heart of medicine.
The information collected is invaluable in supporting NDA applications and also
provide input into the development of value dossiers, cost effectiveness
models and patient evaluation.
Conclusion
RWD is important in assessing the effectiveness of a drug in clinical settings as
compared to RCTs which are done under ideal conditions. Expanded access
programmes provide an opportunity to support the information gained from
RCTs.
The quality of data collected can be improved by designing prospectively how
the data required in the analysis of chosen endpoints is to be collected. There
are presently a lack of guidelines for RWD in the expanded access setting and a
more reliable framework is required for sharing experiences.
Harnessing the use of the latest technology can enhance the quality and also
compliance levels. The analysis of the data from expanded access can be used
to support NDA applications for investigational drugs.
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About the authors:
Adam Walker
Adam is an experienced Subject Matter Expert in the
field of Biometrics currently acting in this capacity for
Synergy. He has a keen interest in the adaptation of
technology to real-world data reporting; specifically
within Clinical Research. With a background in
Pharmaceutical Sciences, he has worked for both
Pharma and CRO’s in a career spanning nearly 20
years in the field.
Please connect on LinkedIn:
https://www.linkedin.com/profile/edit?trk=hb_tab_pro_top
Lovemore Gakava
Lovemore has worked within Clinical Research for
the last 8 years primarily in Statistical Programming.
More recently he has extended his capabilities
following the completion of his MSc in Statistics with
Medical Applications from Sheffield University. He
has worked in the Pharmaceutical Industry and is
currently employed as a Biostatistician at Synergy.
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Who are Synergy?
Synergy is a bespoke CRO delivered by the award-winning market leader in
scientific recruitment, SRG. Our customers turn to us for the considerable cost
savings, increased productivity and the flexibility that our professional services
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We promise excellent results first time, every time by ensuring:
+ A dedicated resource model at competitive rates
+ A dedicated Synergy Clinical Project Manager acting as your primary
point of contact throughout the Biometrics process
+ A stable and highly specialised team of Senior level experts, experienced
in a range of client systems, SOPs and quality documents
+ Clear and transparent resource scalability
For further information, please visit: www.srg.co.uk/synergy
Note to Editors:
SRG is a market leading recruitment company dedicated to the supply of
scientific, clinical and engineering professionals across the scientific-based
industries. Our commitment and passion to provide the right solution first
time, coupled with our specialist sector knowledge, make SRG different from
any other recruitment company. We constantly strive for excellence in all that
we do.
For further information, please visit: www.srg.co.uk
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