A look at the rise of real-world evidence and humanistic patient reported outcomes

Driven by a continued demand for more affordable treatments that better meet patients’ needs, post-marketing research in the healthcare industry has undergone a revolution over the last thirty years.

The goal of post-marketing research has always been to improve the way in which new drugs are assessed for their cost benefits and clinical effectiveness. This is seen from early commercially driven studies of the 1970s and 1980s, characterised by improvements in safety surveillance reporting, through to the adoption of Health Technology Assessment (HTA) and more evidence-based reimbursement evaluations in the 1990s.

Today, post-marketing research is on the cusp of an exciting new chapter in its ongoing evolution, where real-world evidence (RWE) and humanistic patient reported outcomes (PROs) are increasingly supplementing the data gathered through randomised controlled trials (RCTs). In this new era, real-world programmes, including observational studies, pragmatic trials, and health management programmes are playing an increased role in decision-making. These studies provide valuable sources of patient reported real-world data (RWD) that can be used to develop a more accurate picture of a drug’s clinical benefits. And, thanks to advances in technology, the latest digital solutions are helping to improve the efficiency and cost-effectiveness of capturing this RWD compared to traditional paper-based methods.

The rise of safety surveillance and commercial exploitation

In the 1980s, pharmaceutical companies relied, to a great extent, on their sales force to drive the uptake and use of new drugs as part of their post-launch campaigns. Marketing teams would turn post-marketing study results into persuasive information designed to support sales efforts, focusing less on scientific evidence in favour of simple studies that offered physicians an opportunity to assess the clinical usefulness of new products.

The aim of this approach was to accelerate the uptake of new drugs within clinical practice, and there can be little doubt that post-marketing research was successful in meeting this objective. Indeed, in a paper examining this so-called ‘investigator prescriber’ effect, physicians who had been involved in phase IV studies on a new drug would, on average, prescribe 58 percent more of the new product 18 months after the end of the study compared to their control group counterparts.

On reflection, these studies can be thought of as an early attempt to generate RWD and, in some instances, likely resulted in patients gaining access to the right treatment faster. However, their lack of scientific rigor and often dubious operational standards meant that they offered little value as an evidence-based tool for healthcare decision-making.

An increased focus on clinical effectiveness and economic outcomes

Throughout the 1990s, the influence of the pharmaceutical salesforce on physician behaviour experienced a period of sustained decline. The price of drugs was rising, and the cost of care for most global healthcare systems was spiralling out of control.

Against this backdrop, the growing influence of HTAs and the establishment of evidence-driven treatment pathways had a significant effect on the way in which the pharmaceutical industry and their external stakeholders interacted. To this end, more specialist price negotiators at both national and regional levels were introduced.

As a result, the type of post-marketing data that was required changed. The evidence-based hierarchy systems that the HTAs adopted meant that RCTs produced the ‘best’ evidence, and therefore had the greatest influence on healthcare decision-making. However, RCTs were expensive, and the industry was reluctant to invest in them during the post-marketing period when a return on investment for developing the drug was at the top of their minds.

Post-marketing research methods were being altered in other ways, too. New laws, regulations and directives for both clinical research and pharmacovigilance set minimum quality standards and attempted to clarify how post-marketing research should be conducted. The introduction of these guidance documents somewhat restricted the role of observational studies to safety surveillance. The inherent design limitations of observational studies meant that study results were rarely used in HTA decision-making. Although a 2009 guidance document for HTA agencies encouraged the inclusion of observational data in reviews, in a 2015 paper of over 1,800 historical reviews, it was reported that only 6 percent of HTA decisions used data generated from observational studies.

The advent of RWE and humanistic outcomes

So, how has post-marketing research evolved in the 21st century? Today, the field has a new momentum, a much more defined role and strong scientific grounding, largely due to the increasing demands and complexities of market access.
In an influential paper published by the Network for Excellence in Health Innovation (NEHI) in 2015, RWE is described as ‘a new era for healthcare innovation’. While NEHI recognises that good RWE should come from a range of sources, it is likely that pragmatic trials and well-conducted observational studies will have an increasingly important role in informing future healthcare decision-making. However, there are still many barriers to overcome on the road to routinely using RWE as supportive evidence alongside RCTs as the primary decision-making tool.

One of the big hopes for a brighter post-marketing research future is the increased adoption of advanced digital technologies, such as mobile phone applications and wearable devices. These can collect, store and distribute large volumes of real time patient-reported data at a lower cost than the often burdensome and error prone paper-based alternatives.
Such electronic RWD capture platforms, which can be used on patients’ own devices, are more easily integrated into everyday life and can be used to reduce patient burden and improve compliance. Sponsors can also use these platforms to remotely engage with and monitor patients, and collect standardised RWD in real time from different devices supported by a full audit trail. As the quality of RWD improves via the support of these electronic capture methods, so too will the adoption of RWE in healthcare decision-making, with the patient recognising the ultimate benefit.

Post-marketing research has risen from being the poor relation of clinical research to one that is rapidly becoming the vital tool for assessing product benefits in a real-world clinical setting. In the future, post-marketing clinical research departments need to adapt to the evolving nature of the post-marketing research environment. For example, ensuring generalisability – the degree to which the results from the study population are relevant to the treatment population – is becoming the new imperative and driving new thinking regarding study set-up and site and patient recruitment strategies.

Moreover, advances in digital technologies are opening up new possibilities for RWD collection, allowing patients to become increasingly involved in their own healthcare and directly involved in research. This patient-centred approach allows for more holistic RWE-informed healthcare decision-making, bringing the goal of personalised treatment and its healthcare benefits ever closer for individual patients.

Gary Coward is chief operating officer at Synigence Research and Gavin Birchnall is senior solutions consultant at ERT