With the updated references of harmonised standards for medical devices, ISO 14155: 2020 is THE GCP standard for medical device clinical investigations, and since as of May 26th 2021 the MDR fully applies you may want to familiarize yourself and your team with the changes to ensure proper clinical data collection in line with this standard.
The new version has some interesting additions, such as more attention for the relationship of clinical studies with device risk management procedures and the product developmental stages, but also for risk-based monitoring, and guidance on statistics.
The clarification of the relationship of the different types of pre- and post-market clinical studies with the product development stages and the applicability of ISO 14155 (Annex I), in combination with the refined scope and definitions, illustrate the widened scope; Such that the new version of ISO 14155 includes guidance on post-market clinical studies, interventional as well as non-interventional.
The scope indicates that the principles set forth in the standard are also intended for post-market clinical investigations and software medical devices considering the nature of the clinical trial, and the definition of the investigational medical device (medical device being assessed for clinical performance, effectiveness or safety in a clinical investigation) has a note that
“this includes medical devices already on the market that are being evaluated within their intended use in a post market clinical investigation (interventional or non-interventional).”
Also the applicability of ISO 14155 as addressed in Annex I, indicates that
“Depending on the clinical development stage and the type of the clinical investigation design, the principles of this standard be applied in full or in part”,
and that significant deviations should be documented.
So all very much in line with the MDR, that specifies in article 82, that also clinical studies other than the clinical investigations to establish and verify performance, clinical benefits and/ or clinical safety of the device should comply with the basic regulations of GCP.
New is the section on risk-based monitoring, that parallel to the current trends to reduce the study (budget) burden, and, following the corona pandemic, to reduce contact frequency, leaves more room for a combination of on-site and remote monitoring. Very different from the old version that allowed for remote monitoring in “exceptional circumstances” only. The 2020 version specifies that
“Centralised monitoring is a remote evaluation of accumulated data and compliance to provide additional monitoring capabilities that can complement or reduce the extend and frequency of onsite monitoring.”
Note that centralized monitoring is different from remote source data verification, which generally speaking is only allowed when justified and currently is limited to the corona pandemic period and/or pseudo anonymized data (also refer to my other blog post on this topic).
Interestingly in this section on the monitoring plan, there is extra attention for the (local) data-protection regulations, which to my opinion was pretty much covered in the previous version in the section on the Informed Consent, but apparently there was a need to re-emphasize this essential aspect of clinical trial data collection and review following the implementation of the GDPR in May 2018.
One of the most challenging aspects of a clinical study, I always find, concerns the collecting safety data and the ongoing need for alignment with other teams/ departments involved in the review and follow-up of ADE’s/ incidents and device risks, and I am happy seeing the extra attention the new version of the ISO 14155, referencing ISO 14971, is paying to the performance and updates of risk management activities throughout the full cycle of the clinical trial (chapter 6.2 and the new Annex H):
“(Residual) risk(s) to the study participant due to the investigational device and/ or the clinical procedures required by the study protocol shall be weighted on an ongoing basis versus potential benefit …”
Also interesting in this respect is the specific attention for investigational medical device training for users. An essential, and often underestimated, aspect of medical devices, that again should be ongoing throughout all phases of the clinical trial to minimize risks for the study participants involved, but also to ensure functioning of your device as intended.
Terms and definitions have been updated for better alignment with those listed in the MDR. The definition for serious adverse events for example now includes wording that these include a serious deterioration in the health of users, or other persons, and a new definition concerning a serious health threat has been added.
Furthermore there is an almost complete new section on adverse event and device deficiency escalation with more attention for corrective and preventive actions, as well as device deficiencies that could have led to a serious adverse device effect, if no action had been taken or circumstances had been less fortunate. The standard emphasizes that such events should be reported as thought an event occurred. Since, in addition, the standard emphasizes that any person with information that could impact subjects’, users or other persons’ safety, must inform the principal investigator and the sponsor of their concerns, and when combined with the enhanced attention for the clinical trial interrelationship with risk management, you may want to review and amend your safety data collection and review processes following this ISO update, if not already done.
for the study design. Similar to what we saw with MEDDEV 2.7/1 Rev 4, there is much more attention for the statistical substantiation of clinical trials, and the statistical section in Annex A (A7), has been more than doubled. Indicating the leaning towards a higher level of evidence studies with a more solid basis, creating additional challenges for observational studies and leaving less room for exploratory studies.
In conclusion, it seems fair to say that with the third edition of the ISO 14155 we are dealing with a medical device good clinical practices with a wider scope and more guidance on key aspects such as risk management, monitoring and statistics. Very much in line with the overall developments in the EU medical device clinical trial environment including the MDR with a better eye for patient safety, and creating – budgetary – opportunities as well as challenges for SME’s.
Feel free reaching out in case you want to discuss any of the above or otherwise.
May 26th 2021
Note: this post has also been published on my blog.