The International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) recently released a third revision of its E6 Guideline, also known as ICH E6 (R3). This revision introduces new concepts and updates in the realm of clinical trial methodologies, with an emphasis on quality, flexibility, and modernization. Let’s explore the key updates and discuss how they might affect medical writers.
1. Embracing Adaptive Trials: Adaptive clinical trials, which allow modifications to the trial or statistical procedure after its initiation without undermining the validity and integrity of the trial, receive increased focus.
Medical writers must familiarize themselves with the concept of adaptive trials, which can be complex and multifaceted. Understanding these trial designs will be necessary to accurately produce study protocols, amendments, and results, and to position new study design concepts effectively in regulatory documents. Gone are the days of rote writing of 3+3s and other standardized study designs, which could often rely on a content reuse strategy to speed up production.
2. Regular Feedback Integration: Sponsor companies are now encouraged to have more regular and early interactions with health authorities regarding trial design, especially for novel or complex designs.
As sponsors are expected to have more frequent interactions with health authorities, medical writers will need to be adept at incorporating feedback and changes into documents more regularly. This will require flexibility and adaptability, as changes could impact various sections of regulatory documents. This type of approach to medical writing will have wide-ranging implications on resourcing, whereby resources will likely not be able to cover multiple programs that could have overlapping and unpredictable needs. Also, as this type of approach to writing would be a paradigm shift, it should be acknowledged that not all medical writers will want to work this way or will be used to doing so.
3. Quality by Design: There’s an increased focus on “quality by design” principles, which emphasize planning for quality from the start rather than identifying errors or issues retrospectively.
The emphasis on “quality by design” means that medical writers will need to invest more time upfront in understanding the study design and anticipated outcomes and planning and executing the documents. This proactive approach can help identify potential issues early on and ensure that the quality of results reported in regulatory documents is high. Note, however, that the same resourcing implications as noted previously would also apply here, as would the need for dedicated staff in the quality control and quality assurance roles. SOPs, work instructions and tools need to be reviewed now to make sure that they allow for the flexibilities called for in this update to ICH E6 (R3) so that any necessary updates are implemented in advance of Annex 2 being rolled out.
4. Aligning with Clinical Practice: New guidelines emphasize that trial protocols and procedures should be consistent with everyday clinical practice.
To write in a manner consistent with clinical practice and gain an understanding of how what you write affects processes up- and downstream from medical writing deliverables, medical writers may need to engage with clinical research teams and observe what happens at clinical sites as well as what their clinical colleagues do in the day-to-day. A deeper understanding of clinical practice can enhance the relevancy and applicability of the written content. Medical writers will need trainings available on standard of care in the disease areas they are working in as well as access to any clinical practice guidelines and current literature, and the libraries and trainings will need to remain up to date. This may require resources to curate, administer, and document the trainings and materials. The curator will also need to use regulatory and clinical intelligence to document any differences in care at the national or regional level to make sure that the documents will be broadly applicable for all planned trial sites.
5. Leveraging Technology and Real-World Data: The revised guideline encourages the use of new technologies, including artificial intelligence, and the use of real-world data in clinical trials.
As the revised guideline emphasizes the use of technologies and real-world data, medical writers must be conversant with these concepts to be able to write and position real-world data effectively in clinical and regulatory documents. The biggest issue is that while real-world data is a single term, it comprises different concepts collected from many sources including electronic health records, claims and billing activities, product and disease registries, and patient-generated data, among others. Knowing how to write the safety language appropriate for a patient registry protocol does not automatically mean the writer will also know how to examine health records. These are areas where a medical writing specialist, as opposed to a generalist, will excel, and resourcing should be planned accordingly; however, as the use of this type of data increases, medical writing education will need to become available to train more specialists so that there is not an issue of supply versus demand. Likewise, each technology used in conjunction with a trial is likely to be unique; the medical writer will need to know not only the medical writing role but also be able to serve as the technical writer to tie the concepts together and to be the expert on what types of information need to be presented per the applicable regulatory guidelines. This is another area where specialty and additional educational offerings are urgently needed.
While medical writers may have been working with portions of these concepts for some time, the full impact of these updates of ICH E6 (R3), particularly those detailed in Annex 2 of the guideline, remains to be seen, as drafting of the annex is currently underway. Nonetheless, anticipating these changes and preparing can help medical writers and their organizations successfully implement the modernizations called for under ICH E6 (R3) in the field of clinical research.
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International Conference on Harmonization. E6 (R3) EWG – GCP. Accessed 08 June 2023. Available at: ICH Official web site : ICH
United States Food and Drug Administration. Real-World Evidence. 02 May 2023. Accessed 08 June 2023. Available at: Real-World Evidence | FDA