The MDR as well as the current version of MEDDEV 2.7/1 reference ISO 14155 as GCP standard for medical device clinical investigations. Indeed, the 2011 version, but the third edition is in the making, so it can be good to familiarize yourself with what is coming our way, and anticipated for this year.
The current draft has some interesting additions, such as more attention for the relationship of clinical studies with device risk management procedures, and the product developmental stages. Besides that I find the addition of risk-based monitoring, and more extensive guidance on statistical considerations worth noticing.
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, indicate that the scope has widened; Such that the new version of ISO 14155 includes post-market clinical studies, interventional as well as non-interventional.
The scope indicates that the “principles set forth in this document also apply to post-market clinical investigations …”, 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 significant deviations should be documented.
So all very much in line with the upcoming MDR, that already specified in article 82, that also other than the regular pre-market clinical investigations should comply with the basic regulations of GCP.
New is the section on risk-based monitoring, in the chapter regarding the monitoring plan, that parallel to the current trends to reduce the study (budget) burden due to on-site monitoring visits, leaves more room for a combination of on-site and remote monitoring. Very different from the current version that allows for remote monitoring in “exceptional circumstances” only, the current draft 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.”
Interestingly in this section, there is also specific attention for the (local) data-protection regulations, which to my opinion was pretty much covered in the current 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 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 a clinical study (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 important – 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. Last but not least, the new draft version includes more detailed guidance on the
for the study design. Similar to what we saw with MEDDEV 2.7/1 Rev 4 (also refer to my previous blog post on this), 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 looks like with the third edition of the ISO 14155 we are heading for Medical Device GCP with a broader 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, 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.