Introduction:
Until about a decade ago, the focus of evidence generation was primarily targeted towards enabling marketing approval decisions by the regulators, and thus the focus was largely on what needs to be done during the product development stage, prior to approval. Shortly after the turn of the century, the importance of capturing safety (adverse event) data after approval was realized, and this led to the focus on post-marketing surveillance, with respect to data capture, analysis and reporting, as well as the enabling systems and processes. Soon thereafter there emerged the concept of confirming “effectiveness” of the interventions once they are on the market; and the influence on practice, prescription and reimbursement.

Demonstrating and supporting the value of their products and enabling access to therapies have been well accepted as major challenges for the pharmaceutical and healthcare industry. HEOR and Real World data are fundamental to establishing value and hence market access as well. Evidence will link real world data with economic outcomes to demonstrate the product’s value proposition. Thus the entire discipline is often termed as ‘Value Evidence and Market Access’, which comprehensively captures the scope.

Real World Studies, Data and Evidence:
Real-World Data (RWD) is data collected from sources outside of traditional clinical trials. Real-World Evidence (RWE) is the evidence derived from aggregation and analysis of RWD elements. Real World studies are used to understand clinical practice patterns and epidemiology of diseases, and to make inferences related to the product’s long term safety and effectiveness, comparative effectiveness and product differentiation.

Information about clinical practice that can be derived from post-marketing studies/data includes – usage pattern; surgical and medical practice patterns, and how they vary by geography; how well trial results compare with real-world practice; how does the product compare with its competitors (regardless of the efficacy comparisons from clinical trials); adherence to prescription guidelines; doctors of which specialty prescribe the product and for which patient group is the product most prescribed.

Registries (defined as observational studies providing data on patient demographics, clinical management, and patient related outcomes) enable evaluation of clinical and economic outcomes in a real-world setting.

The information obtained from real world data (i.e., real world evidence) helps the innovators and manufacturers devise their marketing strategy, identify the target audience and build a relationship strategy, and make the right business decisions. For the patients, it helps identify opportunities to improve the quality of care, identify patient subgroups that may benefit more from the treatment, and also helps develop tools for patient education.

Market Access:
Manufacturers must demonstrate both clinical effectiveness and cost-effectiveness of the product to succeed once on the market. Proving the effectiveness and making the economic case for a new medicine to regulatory agencies is now the key element that is associated with market access. Market access is no longer simply about getting marketing authorization for the product.

The scope of Market Access includes –

  1. Pricing and reimbursement (achieve optimal price and full reimbursement)
  2. Health Technology Assessment (achieve favourable recommendation from the HTA authority); and
  3. Formulary (achieve referencing in various formularies on the hospital, regional and national levels).

Payers’ perception of drug value is comparative, with respect to competitors’ prices, or the historical price. Thus value-based pricing involves understanding stakeholders’ needs, their key value drivers, and their perception of the impact of the drug relative to competitors. Above all, it requires quantifying the value of the drug and translating it into pricing.

Payers will expect real life evidence to confirm that performance in practice is in line with what was projected at launch. They will also expect new evidence as the competition and environmental conditions evolve. Moreover, the payers will formally assess the value of new indications or line extensions.

Health Technology Assessment (HTA) is a systematic approach to evaluate the properties, effects, and impacts of health technologies or interventions. It is applicable to medical devices, medicines, vaccines, procedures, health services and public health interventions.

HTA considers safety, clinical effectiveness, economic considerations, budget impact analysis, organizational impact, equity issues, ethical issues, feasibility considerations, acceptability to healthcare providers and acceptability to patients.

What do Regulators and Other Authorities say about RWE:
The US FDA released guidance about Patient Reported Outcomes a few years ago. [Reference: FDA Guidance for Industry: Patient-Reported Outcome Measures: Use in Medical Product Development to Support Labeling Claims. Dec 2009.[FDA – Guidance Compliance Regulatory Information]

Recently the US FDA released draft guidance for medical devices in July ’16. It is about how RWD collected from outside the clinical trial process, such as information found in registries, databases, case reports, claims data, and electronic health records (EHRs) should be used when making pre- and post-market decisions for medical devices. [Reference: Draft Guidance for “Use of Real-World Evidence to support regulatory decision making for Medical Devices” (July ’16)]. This draft guidance for medical devices is a good beginning by the US FDA.

The Bipartisan Policy Center in the US recently published a report about Using Real-World Evidence to Accelerate Safe and Effective Cures. [Reference: “Using Real-World Evidence to Accelerate Safe and Effective Cures (June ’16)”; FDA: Advancing Medical Innovation – Bipartisan Policy Center.] The recommendations in this report focus on defining how real-world data can be used to support more efficient and effective drug development and strengthen the FDA’s ability to oversee such progress.

A recent report has called on the FDA to clarify the use of RWD. [Reference: “New Report calls on FDA to clarify use of Real World Evidence (June ’16)”].

World Health Organization (WHO) recently conducted a global survey on Health Technology Assessment by National Authorities. [Reference: 2015 Global Survey on Health Technology Assessment by National Authorities – Main Findings]. The survey was responded to by 111 member states. In summary, various stakeholders are awaiting formal guidance from the regulatory authorities regarding the use of real-world evidence for regulatory decision-making.

Implementing Real World research:
The area of RWE brings all stakeholders together in a collaborative healthcare ecosystem. And it can provide some benefit to several functions of the pharmaceutical co., clinical, medical, commercial, and regulatory. For example, if EMR data of cohorts is suggestive of differential benefit of the treatment in certain subgroups, we would look at clinical trial data, claims data, EMR data, and perhaps also do some observational studies or run a registry to get some evidence of this differential benefit. This could provide insightful competitive analysis and aid commercialization strategies. It could also lead to regulatory submissions in certain geographies. By collaborating with different members of the ecosystem to generate the required RWE several groups can benefit from the outcome.

The opportunities to operationalize real world research and reap its benefits are tremendous. There are inherent systemic limitations that we should acknowledge and attempt to overcome. (1) Experts from many different faculties are required, such as MDs, statisticians, epidemiologists, health economists, IT experts, and medical writers and data managers. As suggested in the WHO survey, there’s a lack of qualified resources in most countries. It may help to consider delivering in a global model, making use of the right resources wherever they are available, along with investing in building capabilities in both the advanced and emerging countries. (2) Large amounts of data involved in real world research present endless opportunities to mine it and derive trends and inferences. But the vastness of the data can also be an impediment if we can’t use technology effectively to enable rapid and real-time analytics. (3) Regulatory guidance around how real world data can be used to make decisions will evolve over a period of time. However, several aspects of Market Access can still be addressed through rational and smart data collection and data analysis founded on sound, basic statistical principles.

Conclusion:
Many stakeholders from around the globe can participate in, contribute to and benefit from this emerging phenomenon of RWE. It’s a powerful tool to help the healthcare industry achieve the primary objectives of patient-centric healthcare, namely, to improve patient outcomes, and to bring drugs and devices into the market faster. Those who can make smart use of available human resources and can make effective use of technology advances will have an edge.