Pragmatic and Observational Research (Sep 2023)
Tactical Considerations for Designing Real-World Studies: Fit-for-Purpose Designs That Bridge Research and Practice
Abstract
Nancy A Dreyer,1 Christina D Mack2 1Dreyer Strategies LLC, Newton, MA, USA; 2IQVIA Real World Solutions, Research Triangle Park, NC, USACorrespondence: Nancy A Dreyer, Dreyer Strategies LLC, 328 Country Club Road, Newton, MA, USA, Tel +1 617 733 9478, Email [email protected]: Real-world evidence (RWE) is being used to provide information on diverse groups of patients who may be highly impacted by disease but are not typically studied in traditional randomized clinical trials (RCT) and to obtain insights from everyday care settings and real-world adherence to inform clinical practice. RWE is derived from so-called real-world data (RWD), ie, information generated by clinicians in the course of everyday patient care, and is sometimes coupled with systematic input from patients in the form of patient-reported outcomes or from wearable biosensors. Studies using RWD are conducted to evaluate how well medical interventions, services, and diagnostics perform under conditions of real-world use, and may include long-term follow-up. Here, we describe the main types of studies used to generate RWE and offer pointers for clinicians interested in study design and execution. Our tactical guidance addresses (1) opportunistic study designs, (2) considerations about representativeness of study participants, (3) expectations for transparency about data provenance, handling and quality assessments, and (4) considerations for strengthening studies using record linkage and/or randomization in pragmatic clinical trials. We also discuss likely sources of bias and suggest mitigation strategies. We see a future where clinical records – patient-generated data and other RWD – are brought together and harnessed by robust study design with efficient data capture and strong data curation. Traditional RCT will remain the mainstay of drug development, but RWE will play a growing role in clinical, regulatory, and payer decision-making. The most meaningful RWE will come from collaboration with astute clinicians with deep practice experience and questioning minds working closely with patients and researchers experienced in the development of RWE.Plain Language Summary: Diagnostics, medical interventions, and health services may not perform as well as expected when used in everyday care. The demand for real-world evidence (RWE) to support evidence-based medicine has been fueled by an explosion of accessible data from health encounters using information that clinicians record during everyday patient care, and from patients, caregivers, and biosensors worn by patients. Real-world data (RWD) is an all-encompassing term referring to data from clinical care and everyday life. RWE comes from coupling carefully curated RWD with strong study design and analytics. The primary use of RWE is to fill evidence gaps about real-world performance for people often excluded or underrepresented in clinical trials such as the elderly, those with co-morbidities, or those who use multiple medications. We provide examples of patient registries, longitudinal follow-up studies, evidence hubs with established data linkage and study-specific record linkage.This paper offers tactical advice about the value of opportunistic study designs, what to plan for in terms of transparency in data generation and management, and how pharmacy claims are being linked with electronic health records and/or patient-generated health data. We also explain that treatment decisions may be made by statistical randomization, not by doctors and patients, but after randomization, naturalistic follow-up can be used, ie systematic data collection from patients as they present for care or using decentralized processes. The most meaningful RWE will come from a collaboration of astute clinicians working with patients and researchers experienced using RWD to support evidence-based clinical practice.Keywords: real-world evidence, effectiveness, evidence-based clinical practice, methods and guidelines, master protocols
