How the use of Patient-Reported Outcomes improves Real World Evidence.
Regulatory authorities such as the Food and Drug Administration (FDA) have the task of making therapeutic innovations available to the public as quickly as possible without neglecting their safety. Furthermore, they have the duty of conducting post-market surveillance to monitor adverse effects and safety of their use in the general population. Subsequent emerging results have the power to aid the formulation of regulatory decisions and health policy/guidelines. It is here that Real World Evidence (RWE) is recently pushing to make its presence felt.
The FDA has touted that such data can be collected and used to support medical product development in clinical trials and in observational studies in addition to current practices. However, the true benefits and validity of RWE remains under debate amongst the medical and life sciences communities. The undeniable potential of Real World Data (RWD) and RWE in the approval of new therapies contrasts with the gold standard: data from randomised controlled trials (RCTs). Is it appropriate to herald RCTs alone, without the acknowledgement of the added benefits RWE could bring to overall product evaluation?
According to the FDA , Real World Evidence is “healthcare information derived from multiple sources outside of typical clinical research settings, including electronic medical records (EMRs), registries, and data collected by personal devices and health applications”.
RWE cannot be fully appreciated without an acknowledgement of the problems associated with RCTs. RCTs conduct research on “filtered” populations that are managed in tightly controlled settings. Such forms of research are conducted under the premise of research outcomes of the chosen sample cohort to represent that of the entire population. Moreover, it is this kind of data that is regarded as having the highest validity and subsequently forms the basis of the majority of clinical guidelines for heterogeneous patient populations.
RCTs are invaluable at illustrating efficacy of a proposed intervention but how good is a therapy in clinical reality, where it is used in a diverse patient population? Intertwining RCT data with that of RWE can aid the advancement of determining the true effectiveness and safety of a drug/device. Such hybrid, efficacy-effectiveness studies can assist in establishing a closer correlation to the real world within a clinical development program.
In addition to the creation of more diverse therapeutic information, Real World Evidence has another charm. Real World Data does not have to be “actively” collected, but can be extracted from registries, EHRs or data gathered from other sources that can inform on health status. Thus making the method very attractive financially. In addition, much larger studies are possible and so more meaningful information can be obtained from them.
Flatiron Health , a healthcare technology company has put this into practice. The group has collected data from over 2 million cancer patients in cooperation with the U.S. National Cancer Institute which now includes 14 of the 15 largest oncological life science companies among its customers. The data captured is used to better assess the efficacy of current oncologic therapeutic regimens to ultimately improve overall patient care.
Despite the increasing recognition of the role that Real World Evidence could potentially play in evaluating the benefits of novel therapeutics, its incorporation in widespread studies has not been universally employed. This can be accounted for as randomised controlled trials remain exclusively as the established standard in drug approval processes.
Challenges remain in convincing all parties involved in therapeutic/medical device development of the benefits of RWE incorporation into product evaluation studies. For example, RWE is only suitable for confirming study results and is not a fully-fledged alternative to RCTs. There is a lack of worthy prospective registries with consistent patient data from which to draw reliable RWE from and initiating them is costly. In addition, there is still no universal consensus on access, ownership or uniform standards for such collected data.
The FDA and the European Medicines Agency (EMA) are promoting the inclusion of Real World Data in therapeutic/medical device research as they have the capacity to enhance learning feedback loops regardless of current adversities. What is interesting is the role that patient-reported outcome measurements (PROMs) can play in creating RWD from which to derive RWE from.
PROMs are instruments with which the effects of a disease or therapy on individual symptoms, quality of life or health status can be assessed directly from the patient’s perspective. They are the gold standard for measuring quality of life (HRQOL) and are also increasingly incorporated into RCTs increasingly incorporated into RCTs. Between 2012 and 2016, 70.3% of FDA- and EMA-approved oncology drugs had studies with PRO-based endpoints with an absence of such endpoints being regarded as problematic for overall interpretation. So if pharmaceutical and medical device companies wish to create thorough results that reflect the product efficacy in everyday clinical use, incorporating PROMs is a potential route in which to achieve this.
PROMs fulfil an essential criterion for the recording of Real World Data and Real World Evidence. They are derived from standardised questionnaires to produce structured data that is easy to interpret to derive informative results. These characteristics predestine them for the use in registers to aid the development and widespread use of RWE to advance therapeutics and medical device development and evaluation.