Clinical Trial Delays in Europe after New Diagnostic Device Regulation
Summary in Thirty Seconds
The EU’s new In Vitro Diagnostic medical devices Regulation (IVDR), implemented last year, intends to protect patients, but it is leading more than half of EU clinical trials to run behind schedule.
There is low awareness of the IVDR and the regulations are complex and uncoordinated across EU member states.
A European Federation of Pharmaceutical Industries and Associations (EFPIA) survey found more than half of clinical trials are currently delayed, impacting up to 42,200 patients, including 27,400 with cancer.
Two-thirds of survey respondents stated that they will consider shifting their clinical trials away from the EU and into other regions if these problems persist.
The EFPIA has proposed numerous recommendations to alleviate the barriers created by the IVDR rollout and to improve access to clinical trials.
EU Clinical Trial Delays
Approximately half of all European Clinical trials are currently running behind schedule, and a significant reason for this is the challenge of dealing with and implementing new regulations for diagnostic medical devices. Such diagnostic testing is fundamental for assessing the efficacy of new medical compounds and devices.
The In Vitro Diagnostic medical devices Regulation
The In Vitro Diagnostic medical devices Regulation (IVDR) came into effect in mid-2022 with a transition period extending into 2025 and is the regulatory basis for introducing and putting into service diagnostic medical devices in the EU. It is intended to improve upon the In Vitro Diagnostic Directive (IVDD)—first implemented in 1998—that had many problems. For example, only 8% of diagnostic medical devices involved certified national body clinical evidence marking, while the IVDR aims to increase that to more than 75%. The IVDR requires a comprehensive description of a device’s use and clinical evidence to support its efficacy as well as strengthened post-market follow-up surveillance. The IVDR is intended to create a “robust, transparent, and sustainable regulatory framework…that improves clinical safety and creates fair market access for manufacturers” while seeking to standardize regulations across the EU market. The complex development process for most types of diagnostic medical devices—that test blood and tissue sampled from the human body—combined with the need to address the new IVDR expanded and upgraded regulations, is making the transition a complicated and time-consuming process.
Problems with the IVDR
A notable problem is that there is little awareness of the IVDR across the EU. The different national systems involved in implementing IVDR have made its implementation complex and uncoordinated, resulting in patient risks and reduced consumer access to the diagnostics the IVDR is regulating. Additionally, as of March 2023, less than half of the national boards are certified to IVDR standards compared to the number previously certified under the IVDD.
EFPIA Survey Results
The European Federation of Pharmaceutical Industries and Associations (EFPIA) surveyed 21 of 32 large pharmaceutical EFPIA member companies and found challenges with the implementation of the IVDR that are delaying clinical trials. This survey described four “big picture” issues related to the IVDR:
Delayed clinical trial initiations and launches;
Reduced access to clinical trials for people in the EU;
Slowed access to new therapies for people in the EU;
Negative impact on other EU initiatives (e.g., Accelerating Clinical Trials EU as part of the CITS).
More specifically, the survey found:
82/160 (51%) clinical trials are currently delayed;
238/420 (57%) clinical trials anticipate delays in the next 3 years of 6-12 months;
These delays will impact up to 42,200 EU patients through not being screened for or enrolled in clinical trials, including up to 27,400 people with cancer, leading over 400 trials to see enrollment shortfalls;
Of the surveyed companies, 71% stated they would consider reducing the number of patients in clinical trials if the IVDR requirements remain unchanged;
84% of respondents said that oncology trials could have delayed launches due to low enrollment, followed by 58% of rare disease trials, and 42% of neuroscience trials.
As many as 89 new therapies could be delayed;
Because of these problems, two-thirds of respondents stated that if these delays persist, they will consider shifting their clinical trials away from the EU and into other regions (e.g., North America, Asia, and Australia).
The EFPIA proposed the following solutions to keep clinical research and innovation relevant and progressing in the EU:
Utilize a voluntary pilot to coordinate Performance Study Applications across EU member states;
Develop and agree upon a common set of principles for Performance Study Applications;
Implement a risk-based approach to studies using diagnostic devices that are low-risk to patients;
Temporarily accept, case-by-case, nonconforming Performance Study Applications;
Clarify IVDR terms/definitions, including in-house testing, to broaden their scope;
Delay the implementation of IVDR for clinical trials using an in vitro diagnostic device.
These recommendations would ease at least some of the barriers put up by the rollout of the IVDR, improving access to clinical trials in the EU. Nevertheless, it is important for pharmaceutical companies considering clinical trials in the EU to be aware of the IVDR as well as the challenges resulting from its implementation, which has the intention of better-protecting patient safety through providing a stronger regulation of innovative diagnostic devices.
 EUR-Lex - 32017R0746 - EN - EUR-Lex (europa.eu)  In Vitro Diagnostic Medical Devices Regulation (europa.eu)  Official J Eur Commun. 1998;331:1–37  Analysing the availability of IVDs in May 2022 - MedTech Europe  Hemasphere. 2022 Jun; 6(6): e724  ivd_manufacturers_factsheet_en_0.pdf (europa.eu)  Clinical Chemistry and Laboratory Medicine (CCLM), 2023 in press  Clinical Chemistry and Laboratory Medicine (CCLM), vol. 61, no. 2, 2023, pp. 224-233  Parliamentary Question | Lack of notified bodies ahead of implementation of the In Vitro Diagnostic Medical Devices Regulation | P-001914/2022 | European Parliament (europa.eu)  efpia_ivdr-survey-slides.pdf