Have you had a look at ICH-GCP E6 (R3)?

Even though it is still a draft, it is good to be prepared for this new version of Good Clinical Practice. This is not just an addendum like R2, but a complete revision of the guideline. Of course, you will find the same spirit and the same requirements, but in a completely different structure. The aim now is not to see this guideline as a single document but as a series of documents with E3 (Clinical Trial Reports), E8 (General Considerations for Clinical Trials), E17 (Multi-Regional Clinical Trials) and Q9 (Quality Risk Management) (see https://www.ich.org/page/quality-guidelines)The principles have been expanded and the responsibilities of the various stakeholders are now in annexes.

How can you prepare yourself as a PM? Let's start with the first concept that was already underlying the previous version: quality by design (QbD). This is a well-known concept that was proposed by the CTTI (Clinical Trials Transformation Initiative Quality By Design - CTTI (ctti-clinicaltrials.org) in 2015. The idea is to start your risk assessment before writing the protocol in order to include mitigation measures in the protocol. Nice idea, but how can you as a PM ensure that this happens? If you work directly with the sponsor, you may be involved in writing the protocol. In this case your role is to challenge the study physician on every operational aspect, e.g. limiting the number of outcomes/endpoints to be collected, ensuring that outcomes are patient-centred and endorsed in outcome core sets (CONSORT Guidelines for Reporting Outcomes in Trial Reports: The CONSORT-Outcomes 2022 Extension | EQUATOR Network (equator-network.org), SPIRIT Outcomes – GUIDANCE FOR CLINICAL TRIAL PROTOCOLS (spirit-statement.org), etc.), to ensure that protocol feasibility is established. Protocol feasibility means ensuring that this protocol is reviewed by potential investigators in all countries/regions where the trial will be conducted, by patient representatives and by any external partners involved in the trial. It will allow you to identify the standard of care and study specific visits/procedures in each country/region, the potential burden on sites and patients and how to overcome it, how to ensure successful patient recruitment and retention, etc. This will improve the quality of the protocol. This takes time, and often you don't get that time, so push back, because a good protocol will make your job easier afterwards, and it will be easier to meet study milestones afterwards. These activities should be part of your planning!

Now if you work in a CRO, you often get the protocol almost final and you have to select your sites and it seems too late to apply QbD principles. So how can you ensure that QbD principles have been implemented? You can challenge your sponsor by asking questions about outcomes, data collection, study procedures, etc., provide feedback on potential operational challenges, gather feedback from patient organisations, ask more scientific questions during site selection about outcomes, data collection, standard of care versus protocol visits, etc. It is your role as a clinical trials expert to alert sponsors. Of course, this will require some investment, but it will be easily compensated if your trial recruitment is successful and you can provide reliable data.

Was it useful for you? Let me know in the comments what you think and if you would like to know more about how to apply ICH-GCP R3.