Clinical Governance : Real World Evidence versus Evidence Based Medicine / Practice

FDA sets out vision to use real-world data in product evaluations

In our centre, we have been interested in and following the concept of Real World Evidence (RWE) derived from Real World Data (RWD) and Real World Use (RWU) propounded by FDA USA, and their relation with Evidence Based Medicine / Practice.

The times are moving for HICs and LMICs, clinicians, researchers, pharmaceutical and technology industry, policy makers, health systems and patients. As Jon asked where does Real World Evidence (RWE) sit in the existing hierarchy of Evidence Based Medicine / Practice.

Courtesy of Jon Brassey on evidence-based-health@jiscmail.ac.uk, we came across this interesting goings-on in FDA USA, that may affect how regulatory bodies and countries approve drugs and devices in health care.

Insight – ‘’The FDA has long recognized that the groups of patients enrolled in clinical trials bear only a passing resemblance to populations treated in the real world. Seeking to eliminate confounding factors, clinical trials enroll patients with fewer comorbidities and concomitant medications than are found in the real world. These clinical trial designs prioritize clear safety and efficacy signals over applicability to real-world populations.

Regulators have tried to tackle the problem from multiple angles. In 2013, the FDA told its staff to push sponsors to run clinical trials in broad populations that mirror those found in the real world. More recently, the agency has sought to leverage technological advances, notably electronic health records (EHRs), to generate more evidence of safety and efficacy outside of clinical trials.

‘The increasing accessibility of digital health data, spurred in large part by the transition to electronic health records (EHRs), together with rising costs and recognized limitations of traditional trials, has renewed interest in the use of real-world data (RWD) to enhance the efficiency of research and bridge the evidentiary gap between clinical research and practice. RWD can be defined as data relating to patient health status or the delivery of health care routinely collected from a variety of sources, such as the EHR and administrative data

History - For hundreds of years, the development of new medical treatments relied on “real-world” experience. Discoveries such as citrus fruit curing scurvy described in the 1700s or insulin as a treatment for diabetes in the 1920s long preceded the advent of the modern randomized clinical trial. What these diseases had in common was a reliable method of diagnosis, a predictable clinical course, and a large and obvious effect of the treatment.

In the late 1940s, the medical community began to adopt the use of randomized clinical designs for drug trials.1The recognition that anecdotal reports based on clinical practice observations were often misleading led to the nearly complete replacement of this “real-world evidence” (RWE) approach to evidence generated using the modern clinical trial model. Although moving medical science toward greater scientific rigor, this transformation to RCT simultaneously diminished the use (and minimized the value) of evidence generated from practice-based observations. Randomization and blinding became the gold standard for determining the effect of treatment. With strict protocol-specified definition of eligible patients, populations studied began to diverge from patients encountered in clinical practice. Patients with wider ranges of disease severity and age, taking a broader range of concomitant medications, and with more and varying comorbidities were not as well represented in clinical trials.

By controlling for key sources of bias, assuring appropriately matched study groups, modern clinical trials support drawing strong causal inferences regarding the efficacy of treatments, and thereby contribute to the substantial evidence of effectiveness necessary for regulatory approval. On the other hand, such trials do have important limitations, including high costs, extensive resource requirements, and often long timelines. Restrictive enrollment criteria and the concentration of trial sites in certain health systems make it challenging for some patients to enroll, including those with comorbidities, especially if mobility or cognitive abilities are affected. Thus, the trial population may not reflect the larger population that will use the drug.’

Further reading on these changes are provided in:

https://www.fda.gov/scienceresearch/specialtopics/realworldevidence/default.htm.

FDA sets out vision to use real-world data in product evaluations.

Real-World Evidence and Real-World Data for Evaluating Drug Safety and Effectiveness.''

.Joseph Ana

AFRICA CENTRE FOR CLINICAL GOVERNANCE RESEARCH & PATIENT SAFETY

@Health Resources International (HRI) WA.

National Implementing Organisation: 12-Pillar Clinical Governance

National Implementing Organisation: PACK Nigeria Programme for PHC

Publisher The BMJ West Africa & Journal of Health Practice

Nigeria: 8 Amaku Street, State Housing & 20 Eta Agbor Road, Calabar.

Tel: +234 (0) 8063600642