Evidence-based medicine has been the mantra for patient treatment and public health for several decades, and has been the guiding principle of the pharmaceutical and healthcare industry for how treatments are tested to generate data and evaluate if they can help patients. To support this effort, regulators have provided a framework to help guide experimentation, data collection and analysis for treatments.
However, since the turn of the 21st century the focus of evidence generation has shifted. The traditional view was to generate the necessary evidence during product development in order to enable marketing approval decisions by regulators. However, now the importance of capturing data after regulatory approval has increased. In addition to the adverse event safety data which is captured as a part of post-marketing surveillance, the need to confirm the effectiveness after the products are on the market has become more evident, particularly with respect to its influence on practice, prescription and reimbursement.
"Real World Data (RWD) can effectively supplement clinical trial evidence when the latter is available from limited data"
Real World Data (RWD) can effectively supplement clinical trial evidence when the latter is available from limited data. Real World Evidence (RWE) is based on patient treatment data from approved medical interventions, including clinical, humanistic and economic data, and is used to make decisions about treatment options, healthcare provider acceptance and a guide for future research and development. Other terms that refer to this concept include, comparative effectiveness research, health economics and outcomes research (HEOR), and observational research. HEOR and RWD are fundamental to establishing value and hence market access as well. Evidence will link RWD with economic outcomes to demonstrate the product’s value proposition.
Real World Evidence
The Food and Drug Administration (FDA) has defined RWD and RWE. RWD is the data collected from sources other than traditional clinical trials; this includes pragmatic and observational studies, retrospective database searches, case report form reviews, patient or disease registries and electronic health records. These data are being increasingly obtained from electronic tracking systems used in healthcare to capture patient experiences during care. RWE is the evidence derived from the aggregation and analysis of RWD elements.
RWD enables judgements to be made on the product’s long term safety and effectiveness. Product differentiation can be established through real world studies as they provide a greater understanding of clinical practice patterns and epidemiology of the disease.
The information obtained from RWD is then useful to a multitude of stakeholders including innovators, manufacturers, practitioners, healthcare providers and most importantly patients. This gives practitioners and healthcare providers more tools to improve the quality of patient care and identify patient sub-groups that may benefit from increased treatment. Whereas, manufacturers and innovators can strategize marketing plans, identify target audiences and build relationship strategies for the target audiences.
Effectiveness, both clinically and economically, must be proven for a product to be admitted to and succeed on the market. This is now accepted as a key element in commercialization of pharmaceuticals, beyond authorization by regulatory bodies.
The scope of market access includes pricing, reimbursement, Health Technology Assessment (HTA) authority recommendations and formulary references on a local and national level. Value based pricing is now a key consideration when marketing a product. This means that the price should reflect the value of the drug. Purchasers will base their assessment of value for money on relative competitor’s prices and historical prices. RWE can provide support to back up pricing after a product launch; this is illustrated in the WellPoint guidelines. The guidelines state any claims made by manufacturers on product performance must be justified, specifically those on cost-effectiveness .The RWE is expected to reflect the claims made at launch and confirm that the performance is in line with those claims.
HTA is a systematic approach to evaluate the properties, effects, and impacts of health technologies or interventions. The main drivers of the HTA decisions are comparative effectiveness and cost-effectiveness. Another consideration is the effect the product will have on the health care budget, including at the regional level. These decisions comprise of inclusion of formularies and negotiation of price discounts.
‘The Regulatory Speak’
The US FDA has released multiple pieces of draft guidance on the use of RWE, acknowledging that despite its inherent problems with reliability and relevancy, it provides paths for effective and efficient drug development. The FDA first looked at patient reported outcomes (PROs), highlighting their use in the development process and supporting labeling claims. Similarly, guidance was released regarding medical devices earlier this year, about sources of RWD and how it should be used in making pre and post marketing decisions.
The FDA is being called to further clarify the use of RWD to support more effective drug development and post-marketing commitments. The report from the bipartisan policy center claims RWD has rarely been used beyond post-marketing surveillance and that the broader use, for example, in label expansions, new indications, or to support new drug applications is not yet routinely considered by the FDA. .
The 2015 World Health Organization’s (WHO) global survey on HTA by national authorities also found that in addition to the paucity of regulatory guidance, RWD is not currently being utilized due to a global lack of qualified human resources, with the majority of countries not having an academic HTA training program.
Real World Research in Practice
RWD can benefit multiple stakeholders in the pharmaceutical industry. Then, alongside clinical trial data, claims data, electronic medical records and observational studies could be used to support commercialization strategies and provide an insightful analysis around competitive advantage and differentiation, leading to regulatory submissions in certain geographies or for certain sub-populations and influencing market access strategies.
The opportunities which could come from the use of real world studies are remarkable, yet inherent constraints may limit its use. Effective use of RWD requires a range of experts, from medical doctors to health economists, yet as highlighted by the WHO survey, there is a distinct lack of qualified professionals. Investing in these capabilities and utilizing them where possible could be highly beneficial in both developed and emerging countries.
Regulatory guidance has not yet matured on the use of real world research and will evolve over time, which can pose problems in its use and the FDA’s assessment of its relevance and reliability. Yet market access decisions can still be driven using sound statistical principles to collect and analyze data.
RWD is a powerful tool that can assist the healthcare industry in patient-centric care by increasing the speed at which drugs and devices come to market whilst also improving patient outcomes. Making effective use of available qualified human resources as well as taking advantage of technological advances can give companies the edge in the competitive healthcare environment.