Leveraging Randomized Clinical Trials to Generate Real-World Evidence for Regulatory Purposes

Leveraging Randomized Clinical Trials to Generate Real-World Evidence for Regulatory Purposes

Washington, 11th July 2019 – Professor David Price, head of The Observational & Pragmatic Research Institute (OPRI; Singapore) and Optimum Patient Care (OPC; Australia and UK), and Primary Care Respiratory Society Professor of Primary Care Respiratory Medicine at the University of Aberdeen (UK), was invited as a speaker to present at the public workshop panel titled “Leveraging Randomized Clinical Trials to Generate Real-World Evidence for Regulatory Purposes”, convened by the Duke-Margolis Center for Health Policy and supported by the U.S. Food and Drug Administration (FDA).

Professor Price presented the topic “Real World Designs and Implications for Causal Inference” to the stakeholder community and panellists including representatives from HealthCore, FDA, University of North Carolina, and Johnson & Johnson. He addressed the unique challenges getting to causal interference with a pragmatic trial using a systematic, investigative and experimental (SIE) study – the MAGNIFY trial – as a case study example. He also highlighted the importance of considering the ecology of care versus the types of patients in such studies.

The MAGNIFY Trial

MAGNIFY (Maximising Adherence & Gaining New Information For Your COPD) was an SIE study in the field of inhaler device technology. It is a novel, pragmatic, cluster randomised, multicentre trial and the first of its kind in Singapore that was conducted by OPRI and commenced in mid-September.

The objective of MAGNIFY was to acquire new knowledge and evaluate whether a novel enhanced adherence package could improve clinical outcomes in patients with poor clinical outcomes and poor adherence to therapy. At present, many negative trials exist in the literature showing that adherence support improves adherence but not clinical outcomes. MAGNIFY was the first study that addressed the pitfalls of past study designs and used a cluster-randomized design to answer a very different study question.

While MAGNIFY’s technology was centred on the Propeller Health add-on to the standard inhaler, the actual study question being answered was whether the adherence package as a whole – comprising the device, the right drugs, and adherence support for doctors in clinical practice – could improve clinical outcomes, rather than just the device. This new package was tested as part of the patients’ environment. This study was made possible by quality improvement programmes running alongside OPC’s network of over 800 primary care sites in the Optimum Patient Care Research Database (OPCRD; https://opcrd.co.uk), which allowed access to electronic health records (EHRs), patient-reported information, and willingness to participate in the research of close to 8 million patients. This allowed for the identification of the right patients for research.

In terms of causal inference, the study populations in MAGNIFY were perhaps the most important. This is illustrated below:

Clinical outcomes of all the study populations were considered in the MAGNIFY trial, instead of just patients who are suitable for and accept the technology, setting this study apart from previous trials.

Professor Price concluded that across all pragmatic trials, the key lies in answering the right study questions.