How do medical device clinical trials differ from drug trials?
- Medical device clinical trials are generally smaller than drug trials
- The type of device and its purpose influences clinical trial design and execution
- Class III devices subject to PMA require clinical trials in order to meet regulatory approval
- Medical device clinical trials are split into pilot studies, pivotal studies and post-market studies
Purpose of a Clinical Trial
Clinical trials for medical devices test the overall performance, safety and efficacy of the device when used for its intended purpose2. Depending on the type of device, clinical trials can be tailored to answer specific questions. Both the safety and efficacy must be assessed, as well as the sensitivity and specificity to ensure the device is in optimal condition prior to market approval2,3.
Medical device clinical trials are crucial to ensure the long-term safety and efficacy of a device amongst the general population. Pilot studies are considered the first-in-human study for the device and vital to collect initial safety and performance data. Subsequently, pivotal studies are carried out to confirm the clinical efficacy of the device, as well as weighing up the risks and benefits of the device through statistical analysis. Finally, post-market studies are key to monitoring the long-term efficacy, safety and usage of the device in the general population. Not only does this ensure the device continues to perform in optimal condition, but it also highlights areas where the device can be improved for future use.
Key Phases in a Medical Device Clinical Trial
Clinical trials for medical devices fall into three categories based on the research objective and trial size: pilot (or feasibility) study, pivotal study and post-market study.
- Pilot study – collects initial safety and performance data
- Pivotal study – determines if the device is safe and effective
- Post-market study – analyses the long-term effectiveness of the device
A single-centre trial (10 – 30 individuals) designed to collect initial data on the safety and performance of the device4. Pilot studies form the foundation for larger, more definitive studies (i.e., pivotal studies) by allowing future clinical research and device modifications to be optimized4. In addition, guidelines for the use and intended population of the device can be refined. Pilot studies increase the likelihood of success in subsequent studies and can be explored under several broad classifications: process, resources, management and scientific5.
Process – assesses the feasibility of processes crucial to the success of the main study, for example: recruitment rates, retention rates, failure/success rates and eligibility criteria5
Resources – assesses time and budget problems likely to occur during the main study, for example: How long will it take to fill out all of the study forms? Are the devices readily available when required? Can the software used to collect data read and understand that data?5
Management – assesses the potential human and data management issues, for example: Do participating centres have any challenges with managing the study? Do the study personnel have any challenges? Is there sufficient space on data collection forms to collect all of the data obtained? Does the data show too much or too little variability?5
Scientific – assesses the treatment safety, response, dose and effect, for example: Is the device safe for use? Do participants respond to the device?5
A moderately large trial (up to 1000 participants) that definitively evaluates the safety and efficacy of the device4,6. Pivotal trials run with the sufficient numbers of participants required to support a hypothesis-driven study6. Data collected can include laboratory and facility details for device production as well as data from clinical and nonclinical investigations4. Prior to market approval, the data collected must align with well-defined measures of safety and effectiveness set out by regulatory authorities.
Following approval, the device undergoes post marketing surveillance in the general population (more than 1000 participants)7. The device is monitored for any safety and performance issues and further information regarding long-term adverse reactions, optimal use and effectiveness of the device is gathered7. Post-market studies ensure the device continues to be safe and effective, and that actions are undertaken if the risk of using the device outweighs the benefits4,7. Opportunities to improve the device are also highlighted.
The Importance of Evaluation in Clinical Trials
Based on the class of medical device, ongoing clinical evaluations may be necessary. Clinical evaluations involve the assessment and analysis of clinical data to verify the safety and efficacy of a device8. Initially, clinical evaluations are performed during R&D to test whether or not further clinical investigation is required. Then, during device use, clinical evaluations are repeated periodically as new safety, performance and efficacy information is obtained8. In the evaluative process, devices are often separated into either diagnostic or therapeutic devices. For diagnostic devices, evaluations are divided into 4 groups: technical accuracy, diagnostic accuracy, diagnostic therapeutic impact and patient outcomes9.
Essentially, clinical evaluations must demonstrate that the device works as it should under normal conditions, and that adverse effects are minimised to an acceptable level when weighed against the benefits of the device. During post-market surveillance, manufacturers are responsible for implementing surveillance programs to monitor the safety and clinical performance of medical devices as part of their Quality Management System. Data collected (e.g., safety reports) is communicated to conformity assessment bodies and regulatory authorities, so that clinical evidence regarding device use, warnings and precautions can be updated accordingly. In addition, data obtained from clinical trials is often collated in public databases, a requirement set out in international standards (ISO 14155) and by authorities like the FDA.
Medical device clinical trials can be split into pilot studies, pivotal studies and post-market studies2. This enables the device to be assessed from the early stages of R&D to after the device has been approved for use in the general population. The relative time and cost of getting a device from the research and development (R&D) phase into the marketplace varies significantly when compared to the standard drug pipeline1. Typically, it takes 10 to 15 years for a potentially therapeutic substance to become an approved drug ready for human consumption1. Such a development costs millions of dollars and involves pre-clinical testing, clinical trials, and post-trial regulatory approval by regulatory authorities1. Alternatively, the approval of medical devices is much faster, averaging 3 to 7 years, as well as being generally less expensive than drug developments1. Medical devices that fall into lower-risk class I and class II devices do not normally require clinical trials for approval2. For high-risk class III medical devices subject to post-market approval (PMA), clinical trials are crucial to prove the device is safe and effective2.
- Van Norman, G. (2016) Drugs, Devices, and the FDA: Part 1. JACC: Basic to Translational Science, 1(3), pp.170-179.
- Van Norman, G. (2016) Drugs, Devices, and the FDA: Part 2. JACC: Basic to Translational Science, 1(4), pp.277-287.
- Shreffler J, Huecker MR. Diagnostic Testing Accuracy: Sensitivity, Specificity, Predictive Values and Likelihood Ratios. [Updated 2022 Mar 9]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022 Jan.
- Ravichandran, R., Balakrishnan, R., Batcha, J., Ravi, A. and Sam, N. (2020) Medical device: a complete overview. International Journal of Clinical Trials, 7(4), p.285.
- Thabane, L., Ma, J., Chu, R., Cheng, J., Ismaila, A., Rios, L., Robson, R., Thabane, M., Giangregorio, L. and Goldsmith, C. (2010) A tutorial on pilot studies: the what, why and how. BMC Medical Research Methodology, 10(1).
- mddionline.com. (2022) Chartting a Course in Medical Device Clinical Trials. Available at: https://www.mddionline.com/rd/chartting-course-medical-device-clinical-trials
- Fatima, J. and Rossi, M. (2022) Regulatory challenges and investigational device exemption protocols for fenestrated and branched EVAR in the United States. Seminars in Vascular Surgery.
- European Commission Enterprise and Industry Directorate General. (2009) Guidelines on Medical Devices Clinical Evaluation: A Guide for Manufacturing and Notified Bodies. Available at: https://www.imdrf.org/documents/ghtf-final-documents/ghtf-study-group-5- clinical-safetyperformance
- Van den Bruel, A., Cleemput, I., Aertgeerts, B., Ramaekers, D. and Buntinx, F. (2007) The evaluation of diagnostic tests: evidence on technical and diagnostic accuracy, impact on patient outcome and cost-effectiveness is needed. Journal of Clinical Epidemiology, 60(11), pp.1116-1122.