Real World Data/Real World Evidence fostering Clinical Research
Dr. Natalia Haraszkiewicz-Birkemeier
Registered Sci Exp for EC I Public/Industrial Health Ecosystems I HTAR 2021/2282丨Regulatory, Policy I K4P I FMVA/Investments Advisor I EWE Exp Mentor丨Sr Sci & PL promoting Innovation in HC丨Game changer丨PhD/MBA
‘Healthcare is experiencing a patient data explosion...'
Recently I had the privilege to participate in a webinar organized by the Polish Association for Good Clinical Practice (GCPpl) in the framework of the Working Group integrating IT technologies and mHealth solutions.
I reflected on opportunities and challenges of Real World Evidence (RWE) and Real World Data (RWD) in the context of clinical research. Even though randomized clinical trials are still the gold standard in the drug registration process, RWD and consequently RWE are becoming an increasingly desirable component of reliable clinical knowledge about safety and side effects of novel medicines, treatment standards and cost effectiveness.
Clinical Trials in rare diseases
Rare diseases, as defined by the European Union, affect less than 5 out of 10,000 people. Over 7,000 rare diseases impact as many as 30 million habitants in the European Union, which constitutes a considerable challenge for the clinical research and pharmaceutical sectors.
More than 80% of all rare diseases have a genetic origin, and 60% of new diagnosed patients with rare diseases refer to paediatric populations.
More than 80% of all rare diseases have a genetic origin, and 60% of new diagnosed patients with rare diseases refer to paediatric populations. Until 2016, the European Medicines Agency (EMA) granted the orphan designation to 133 medical technologies.
Clinical trials for orphan drugs are often smaller than those of non-orphan drugs, and they require the development of efficient trial designs relevant to small populations to gain the most information from the available data.
In many cases, prospective, single arm, open label, uncontrolled clinical trials are leveraged which are additionally supplemented with real data from multiple clinical studies and medical registries. This allows for more accurate health technology assessments (HTAs), especially when the results of individual studies are inconclusive.
Sources of RWE data
According to the Professional Society for Health Economics and Outcomes Research (ISPOR), an organization that consolidates pharmacoeconomic research experts, the sources of RWE data embrace:
Applications
Nowadays, Real data are an important source of information for various stakeholders, including drug manufacturers, medical centres and individual patients. In the US in 2020, 78% of the applications for approval of new drugs, New Drug Approvals (NDAs) and Biologics License Application (BLAs) contained RWE data. In the EU, out of 1145 registered clinical study data administrated by The European Network of Centres for Pharmacoepidemiology and Pharmacovigilance (PAS), 50% were used in the drug registration process. Leveraging of RWE in healthcare might generate savings of up to 15% as indicated by the Polish-Swiss eHealth framework.
Exhibit: Current mechanisms of access to RWE.
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RWE research can be used during the early drug development process for the identification of patients with chronic (genetic) diseases, selection of clinical trial endpoints and patients’ recruitment. RWE studies can fill the knowledge gaps by providing comparative arms and answering initial questions about the accurate treatment pathways. At a later stage, those data can be used to demonstrate the real benefits of a treatment, giving an advantage in price negotiations. Up till now, RWE data have much greater use in the post-registration phase. 50-60% of the marketing authorization applications (MAs), implementing RWE are associated with efficiency and safety of novel medicines and patients’ quality of life (QoL).
Exhibit: Real World Outcomes through product development lifecycle.
Between 2011 – 2019 the number of reimbursement applications based on single-arm studies increased worldwide 13 times over the period, where 65% of all cases were related to oncological or hemato-oncological indications. Important determinants of positive reimbursement decisions were the status of a rare ('orphan') disease, 58% of the notifications concerning the so-called orphan drugs received positive HTA recommendations, and the use of external comparators (RWD), optional to the assessed intervention.
Exhibit: Single arm trial submissions to HTA bodies.
When to discuss data from medical records
EMA and FDA regulators prefer disease registries to product registries because the former allow several therapies to be benchmarked. While there are three points to discuss utilization of medical registries with regulatory agencies, generally health authorities highlight the importance of an early dialog in the regulatory process of drug registration.
Nowadays, registries are becoming one of the best ways to collect data on long-term clinical outcomes, which has an especially high relevance during the monitoring of patients treated with Cell and Gene Therapies (CGTs), defined in Europe as Advanced Therapies Medicinal Products (ATMPs) up to 15 years after receiving these innovative treatments.
Although RWD/RWE offer high quality complementary assessments of the effectiveness and safety of orphan drugs, there are however several limitations which need to be considered. In one of the surveys, interviewed healthcare professionals solicit more support and additional guidance from health and regulatory authorities and better interoperability of RWE data across Member States.
An important question arises: How to further leverage and maximize the potential of RWD / RWE?
Resources