The ICH guideline for Good Clinical Practice states that sponsors should evaluate identified risks against existing risk controls by considering “the likelihood of errors occurring, the extent to which such errors would be detectable, and the impact of such errors on human subject protection and reliability of trial results” (ICH E6 R2).
If the first step in risk management and control is to identify risks as well as associated mitigation strategies then ask yourself; how would you score the impact, probability and likelihood of a pandemic? High, medium, low? How would the risk be addressed? Avoid, Transfer, Mitigate, Accept? How many sponsors have even addressed the risk of a pandemic (be honest)?
A few short weeks ago typical risks to be mitigated in a clinical trial may have included protracted regulatory approval, absence of key personnel, slower than expected recruitment, higher than expected subject drop-out rate. The risks would have been identified and plans implemented commensurate with the risk; a risk log would have been created and periodically reviewed and the risk would have been closed when no longer applicable. Simpler times.
Now that most improbable of risks, a pandemic, is a harsh reality. Any decision to adjust clinical trial conduct as the pandemic escalates should be based on risk which needs to be assessed and documented on an ongoing basis. The risk assessment should focus on subject safety and data integrity and when the two conflict, subject safety prevails.
As the pandemic takes hold, we may expect to see data quality and patient safety issues due to missed visits as subjects are required to self-isolate and they may even have to discontinue; increase in protocol deviations, reduced capacity in local laboratories; site staff may be required to self-isolate or may be redeployed and with fewer site staff there may be fewer visits performed; delays in case report form entry or serious adverse event reporting; there may be delays in Investigational Medicinal Product (IMP) provision due to travel restrictions and an uptake in adverse event reporting as subjects report flu-like symptoms.
Guidance to support sponsors during the pandemic have been released by the regulators and with a very strong message; sponsor responsibilities under GCP do not stop. What remains constant is that the rights, safety and wellbeing of participants should be assured, and the data collected should be reliable.
In the wake of travel restrictions and quarantine orders, sponsor oversight activities including monitoring and quality assurance activities need to be reassessed. Remote monitoring with the proviso that subject confidentiality is not breached and that it does not unduly burden the investigator site at this challenging time has been recently supported by the MHRA, again the risk and impact of any changes to the monitoring strategy needs to be documented as part of the trial risk assessment:
As the pandemic bites we have taken a leaf out of the regulator’s book. Staying true to our mission statement, ADAMAS are doing what we can to support the healthcare industry. We have expanded our remote service offering to include the Quality Investigator Site Assessment (QISA) to monitor compliance during these quite exceptional times. The QISA allows the highest possible degree of sponsor oversight and reassurance and is supported by our encrypted document sharing platform to enable secure access to documents.
If you would like to learn more please download our guide ‘Quality Investigator Site Assessment (QISA)‘.
The novel coronavirus needs a novel approach to assure that patient safety, data integrity and scientific validity are consistently maintained. ADAMAS is well placed to assist in this regard via our remote service offerings, not only assisting our clients to maintain compliance oversight, but also providing peace of mind that while we navigate these current challenging times together compliance oversight activities can continue.
To find out more about our remote auditing services and how ADAMAS can support your audit program, please feel free to call us on +44 (0)1344 751 210 in Europe, +1-919-341-3361 in the US; or email us at firstname.lastname@example.org.
In the interim please refer to our most recent blog on remote audits and stay safe:
Remote Auditing – A Viable Alternative in Challenging Times