Connecting medical device clinical trials to real-world data (RWD) helps demonstrate efficacy, safety and cost-effectiveness.
Mehdi NajafZadeh, Medidata
Medical device and diagnostics manufacturers face mounting pressure from regulators, payors and providers to provide more holistic evidence to demonstrate the efficacy, safety, and cost-effectiveness of their products.
To address these increasing requirements — as well as accelerate study timelines and reduce clinical trial burden — medical device sponsors are seeking innovative solutions. Connecting clinical trials to real-world data (RWD) is an effective approach to capture the information needed and enhance evidence generation during and after a trial.
Regulators encourage the use of RWD to inform approval and market access decisions
While medical device manufacturers have long-relied on real-world evidence (RWE) for regulatory submissions, recent guidance from regulators around the world is accelerating the use of RWD and RWE in clinical and device development. The U.S. regulatory push for RWD use began in 2016, when the 21st Century Cures Act required the FDA to develop guidance on the use of RWD in evidence submissions for medical devices. RWE is now prevalent in clinical development. -As of mid-2021, RWE has been used in 96% of all approved new drug applications and biological license applications in the U.S.
This increased acceptance has provided the investment and regulatory support for use of RWD in medical device studies. Examples of this include:
- Accelerated investment: The FDA has established the National Evaluation System for Health Technology (NEST), a public-private collaboration to reduce the time and cost of generating evidence by linking and synthesizing data from disparate sources to support regulatory approval and postmarketing surveillance for medical devices.
- Regulatory support: To demonstrate the value of RWE, FDA’s Center for Devices and Radiological Health (CDRH) recently published 90 examples of the successful inclusion of RWD in regulatory submissions between 2012 and 2019. Thirteen of these examples outlined linkage of registry data to administrative claims data, such as from the Centers for Medicare and Medicaid Services (CMS).
Linking clinical trials and RWD
Linking clinical trial data to RWD at the patient level can help medical device manufacturers develop a deeper understanding of the longitudinal patient journey than ever before.
Regulators are enthusiastic to link clinical trials to RWD to reduce gaps in insights and evidence. Said FDA Commissioner Dr. Robert Califf at the 2023 J.P. Morgan Healthcare Conference: “It’s not hard to imagine that the combination of the patient’s medical record and the use of digital technologies at home would give a much better portrait of what’s going on with a human being than going to a research clinic once every three months and having a study coordinator try to figure out what happened during that intervening period.”
Sponsors are unlocking value from linked clinical trial data and real-world data in at least five ways:
- Longitudinal follow-up with minimal burden: Post-authorization surveillance is critical to fully understand the long-term effectiveness and safety of medical devices. However, the high cost and burden of clinical trials pose significant challenges for medical device manufacturers to sufficiently meet regulatory requirements for long-term tracking. Linking trial patients to RWD allows sponsors to reduce patient and site burden by monitoring trial effectiveness and safety outcomes passively, even after trial completion. This capability becomes especially important for diagnostic and device trials, considering that many clinical benefits and safety signals emerge years after market authorization.
- Generate evidence for patients lost to follow-up: The loss of patients to follow-up may prevent a trial from reaching the statistical significance needed for regulatory approval. Lack of insight about patients’ outcomes, especially when attrition rates are differential between treatment arms, can also result in bias and undermine validity of findings. Linking clinical trial participants to their RWD at the patient level helps investigators capture key outcomes like survival, disease progression and changes to treatment pathways, or to understand underlying reasons for loss to follow-up.
- Validate and calibrate real-world endpoints in pragmatic trials: To ensure pragmatic studies using RWD are meeting regulatory standards, sponsors will need to mitigate potential data quality risks, resulting in potential biases in RWD studies. For example, to understand discrepancies between clinical trials and real-world observations, investigators can utilize patient-level linkage to validate RWD-based endpoints against trial-based adjudicated outcomes and improve measurement algorithms used in RWD. This would increase confidence in pragmatic study designs that rely on RWD as a quicker, lower-cost method of evidence generation.
- Measuring healthcare resource utilization (HCRU): Medical device manufacturers can rarely collect HCRU and cost data during the trial because of practical limitations such as patient and study site burden. Although critical for coverage decisions and payor negotiations, measuring these endpoints can require years of waiting for sufficient real-world evidence to accumulate post-commercialization. By linking clinical trials to RWD such as insurance claims and payment data, manufacturers can accelerate the time to generate evidence on HCRU, cost, and cost-effectiveness of their products.
- Enable adaptive trial design and reuse of trial data: Medical device manufacturers design clinical trials to evaluate pre-specified outcomes in select patient populations. After launch, however, sponsors often need to change the procedure or design based on the early clinical outcomes or physician experience during implementation and deviate from the original trial protocol. Clinical trial data linkage can expand researchers’ flexibility in adapting to these changes by enabling them to re-use trial data and provide insight into additional outcomes and variables without increasing patient burden for active data collection.
Clinical trial data linkage can generate interconnected and re-usable data assets to support these use cases. However, until recently, operational hurdles, technological limitations, and data privacy concerns have prevented sponsors from efficiently linking their clinical trials to RWD at scale. To address these issues, commercialized technology solutions are linking clinical trials to RWD seamless, secure, and scalable.
Linking medical devices and diagnostic trials to RWD can substantially enhance depth and efficiency of evidence generation, and is a technique that is being increasingly adopted by the industry. To avoid missed opportunities, obtaining essential data elements such as patient consent need to be embedded early on in the process of trial design and implementation. Medical device and diagnostics manufacturers need to build data linkage into their clinical trial planning today to remove silos and mobilize efficient use of data sources for better clinical evidence generation in the years to come.
Mehdi NajafZadeh, Ph.D., is a senior director at Medidata with experience in investigating new methods that can bridge the gap between randomized and non-randomized data sources. Before joining Medidata, he was an assistant professor of medicine in the Division of Pharmacoepidemiology and Pharmacoeconomics at Brigham and Women’s Hospital and Harvard Medical School, and the principal investigator of NIH- and FDA-funded projects that aimed at linking randomized controlled trials to RWD.
The opinions expressed in this blog post are the author’s only and do not necessarily reflect those of Medical Design & Outsourcing or its employees.