What kind of evidence is most appropriate for new medical devices entering the market?
What kind of evidence is most appropriate for new medical devices entering the market? Specifically, when are randomized clinical trials not the best choice for new therapeutic devices, and what should we do instead?
This initiative brings together the expertise of IDEAL members with backgrounds in ethics, surgery, devices, health economics and trials methodology to address a key issue in medical device regulation:
Nearly all medical products which do not work solely through chemical action, from condoms to surgical robots, are regulated as medical devices. Their huge range of purposes, mechanisms of action and inherent risk pose unique challenges for regulation.
The medical device industry has grown rapidly, with device sales nearly doubling over 10 years to US$172 billion in the United States (2015) and €110 billion in the European Union (EU) in 2015.
The standard of evidence currently required for approval of medical devices is generally lower than for drugs. Reforms to device regulations in the US and the EU, such as the 2017 EU Medical Device Regulations (MDR) set a stricter burden of proof of clinical evidence of effectiveness for all class 2b, 3, and implantable devices, but neither the types of studies nor the reporting standards required are clearly defined, creating uncertainty about the evidence required to achieve certification.
High-profile implantable device failures and adverse effects, as have been seen with hip devices, silicone breast implants and vaginal mesh, have fueled concerns about the adequacy of clinical evidence needed for market approval and calls for more rigorous evidence of devise effectiveness and safety.
Calls for more rigorous evaluation lack clarity about what kind of evaluation is most appropriate, however, and are commonly interpreted as meaning more randomized controlled trials (RCTs). Internationally, drug licensing systems effectively require RCT evidence of benefit or equivalence for nearly all new drugs. There is, therefore, a case for suggesting that all new devices should also require RCT evidence, but RCTs are increasingly costly and time-consuming, whilst device commercial life-cycles are often short, and many devices entering the market make no claim of superior effectiveness, claiming benefits in other areas, such as cost or durability. The primary concern of device regulation is also the risk of harm, for which other study designs are more appropriate evaluation tools than RCTs.
Importantly, the vast number of new devices introduced per year, and the frequent modifications some devices undergo (ex Software as Medical Devices, or SaMD) greatly exceeds the available capacity for conducting RCTs. Therapeutic devices also share with surgical operations and other complex interventions several important characteristics which make RCTs challenging to perform and necessitate specific preliminary studies, as highlighted in the IDEAL Framework. An RCT may not be appropriate for all new devices, but what should we do instead?
In “Beyond the RCRT,” we draw on ethical principles and clinical considerations to develop an evidence-based framework and sequential decision-making algorithm for identifying when an RCT should be performed to evaluate new therapeutic devices, and when other methods such as observational study designs and registry-based approach are acceptable.We offer a principles-based framework and decision-making aid for identifying when RCTs should be performed to evaluate new therapeutic devices and what type of clinical evaluation should be required when they are not. These recommendations are guided by the principles of the IDEAL-D framework for medical device evaluation and would create a safer system for monitoring innovation and facilitating more rapid detection of potential hazards to patients and the public.
Want to know more about our algorithm, and “Beyond the RCT?” See recordings of our presentations in the Society for Clinical Trials’ 2020 Conference https://www.sctweb.org and the 2021 IDEAL Conference http://www.ideal-collaboration.net/ideal-conference-2021/ Also, watch this space for our publication, currently under review at Annals of Surgery.
Arsenio Páeza,b, Maroeska Roversc, Katrina Hutchisond, Wendy Rogersd,e, Baptiste Vaseyf, Peter McCullochf