Protocol Development #16: DCTs, CIDs, Patient Engagement, DE&I, and Study Design

After 15 editions I've finally had some constructive feedback (thank you)! Namely, to help everyone see what type of resource it is, I've added the type in square brackets at the beginning of the paragraph. Incidentally, this gives an easy metric to report

 ** PD#16: 7 articles, 2 webinar recordings, 2 blog posts, 1 book, 1 ICH guideline, 1 conference proceeding **

Overall, there's been some very interesting resources released, if I had to pick my top 4 - they would be the 2 DCT webinar recordings, Leyens et al, and Coskinas et al. The webinar recordings were both surprisingly compelling and engaging and made for a useful change in tack compared to reading articles. That being said, Leyens et al provided a fascinating industry perspective on how to implement DCT components into your study; and Coskinas et al provided an interesting analysis on just how many protocols undergo important change in-flight (although limited to Australia, there is no indication that the results cannot be extrapolated to other similar countries).

DCTs

[Webinar recording] The DiMe Society Journal Club saw Charmaine Demanuele and Pirinka Georgiev from Pfizer Inc discuss their research paper on Considerations for Conducting Bring Your Own "Device" (BYOD) Clinical Studies (article link in PD#12). As novel tools for data collection, the BYOD option has potential for being more user-friendly by allowing the participants to use technology they're familiar with; BYOD is posited to ensure better participant compliance and potentially reducing the bias that comes with introducing new technology. The presenters say that the time for BYOD is now and by using their adoption framework study teams can successfully embed a BYOD approach in their study (and by extension, the protocol). Overall, the presenters depth of understanding on DHTs shines throughout - yet they deliver an engaging presentation that should provide some take-home messages for all viewers.

[Webinar recording] ActiGraph's CEO Jeremy Wyatt moderated a discussion with Robin Harris, Marie McCarthy, and Elan Josielewski about the challenges of - and best practice for - deploying and managing DHTs in studies: Operationalizing Digital Health Technologies: Successes and Failures in Clinical Research. The goals of the discussion - increasing audience knowledge, equip audience members with the right questions to ask when designing the study, and to inspire the audience on using DHTs - held true throughout the hour-long webinar. The webinar starts with an orientation by Jeremy around the FDA DHT guidelines and the DiMe four stages of operational considerations when deploying remote monitoring. Discussion kicked off with a focus on study participants and the importance of understanding and explaining the approach and why such an approach has been taken. Protocols came up - the key takeaways were 1) functionality and usability of DHTs need to be aligned with the study features, 2) DHTs requirements/vendor discussions need to start as soon as possible and must be prior to protocol finalization.

[Article - Case Study] Simmons et al published an article From hybrid to fully remote clinical trial amidst the COVID-19 pandemic: Strategies to promote recruitment, retention, and engagement in a randomized mHealth trial that details the lessons learned from their full DCT study. By transitioning from a hybrid to fully-remote study designs, the authors were able to improve screen failure rates by 7%, activity adherence by 20-30% and have a study completion rate of 82%. As the number of mHealth studies continues to grow - the lessons learned here may provide some inspiration to those looking to conduct similar studies with alternative mHealth interventions.

[Article - Research] Suman et al published an article on A cross-sectional survey on the early impact of COVID-19 on the uptake of decentralised trial methods in the conduct of clinical trials where 18 organizations provided feedback on the impact of COVID-19 on their clinical studies. Although the small sample size (and some respondents only representing units/departments rather than whole organizations) limit the conclusions being drawn, figure 2 provides an interesting view on how remote method adoption changed with COVID-19, namely pharmaceutical companies showing a higher degree of implementing remote methods to mitigate COVID-19, compared to CROs, research networks, technology companies, and universities.

[Article - methodology] Leyens et al published an article on The COVID-19 pandemic as a catalyst for innovation: a regulatory framework to assess fit-for-purpose innovative approaches in clinical research. As a follow on from Suman et al above, this methodology article provides an industry perspective/roadmap for how one pharmaceutical organization (Roche/Genentech) implements DCT components in a study. Their approach centers on 3 pillars - context, evidence, and feasibility. Table 1 provides a summary of the DCT components considered, and table 2 provides the assessment framework. To reinforce the proposed framework, the authors summarize 3 case studies. For those working in drug development, this should form part of your critical reading list.

CIDs/Master Protocols

[Article - Review] Pericàs et al published a review on Platform trials to overcome major shortcomings of traditional clinical trials in non-alcoholic steatohepatitis? Pros and Cons. In the review, the EU-PEARL NASH team outline how platform study designs with adaptive design elements can be superior in addressing the challenges facing NASH studies - and indirectly making the case for the EU-PEARL NASH program. Although the review itself doesn't provide any truly surprising revelations - and a lot of considerations that are applicable to any platform study involving drug development stakeholders, the perspective from a group that is actively engaged in setting up a platform study for NASH may serve as validation or at the very least, reassurance to others working in a similar space.

Patient Engagement

[Article - Commentary] Izmailova and Ellis' commentary on When Work Hits Home: The Cancer-Treatment Journey of a Clinical Scientist Driving Digital Medicine gives a fascinating insight into the patient perspective, not least because the author - as the patient (and digital biomarker company employee) - collected and analyzed (with a colleague) her own heart rate variability (HRV) and step count data. The anecdotal evidence from the N=1 study of what could be considered an enthusiastic early adopter highlight the need for truly integrated data collection dashboards that can help patients understand and communicate their collected data with relevant stakeholders - such as their treating physician.

Diversity, Equity & Inclusion

[Book] The US National Academies of Sciences, Engineering, and Medicine (NASEM) published a book on Improving Representation in Clinical Trials and Research: Building Research Equity for Women and Underrepresented Groups. The free 280-page resource covers why a diverse representation in clinical research matters, policies to improve diversity, barriers and facilitators to inclusion, and recommendations for improvement. I've yet to get really started but at a glance it's important reading for those wanting a deeper understanding on how we - as clinical researchers - can support inclusivity. In case you missed it - the MRCT's annotated CPT for DE&I (covered in PD#13 and Diana's October newsletter) gives protocol authors a great starting point to discuss DE&I with study teams.

Clinical Study Design

[ICH Guideline] The ICH released a new guideline titled A selective approach to safety data collection in specific late-stage pre-approval or post-approval clinical trials. In this new E19 guideline, products with a well-understood and documented safety profile may forego comprehensive safety data collection in favor of a more selective approach. In the guideline, practical considerations for selective safety data collection indicates that regulatory authority engagement is a likely requirement so may impact protocol authors in that the starting SoA may evolve as the regulatory authority feedback unfolds. In addition, the guideline may also impact benefit-risk discussions since implementation of any selective safety data collection will likely include some careful risk consideration.

[Article - Research] Coskinas et al published an article on Changes to design and analysis elements of research plans during randomised controlled trials in Australia where the researchers analyzed the protocols from 181 eligible studies (124 studies with full protocol available, 57 studies without the protocol available). From this analysis set - approximately 2/3 were drug/device studies, about half covered cancer, mental health, respiratory and musculoskeletal indications, and almost all were superiority parallel arm studies. Of the 118 protocol-available studies with important changes identified or suspected (95%), the primary analysis method had been changed in 83 studies (70%), the sample size in 60 (51%), the eligibility criteria in 59 (50%), the primary outcome in 52 (44%), the analysis set population in 29 (25%), and the primary comparison in eight of eleven (73%) multi-arm trials.

[Conference proceeding] Matsuda et al published an conference proceeding from the 2022 Portland Internaltional Conference on Management of Engineering and Technology (PICMET) titled Entrepreneurial Orientation on Clinical Development in Pharmaceutical Industry: Fixed-Model Analysis. The authors indicate that pharmaceutical advancement needs two types of organizational capability: for basic research - serendipity and happenstance, for clinical research - go/no go decision-making and protocol design capabilities. In reference to protocol design capability, the authors note that this has a significant effect on the interpretation and duration of study results, and is a fundamental capability for product lifecycle strategy. In their analysis of entrepreneurial orientation, the authors propose two recommendations for enhancing innovation and risk-taking: 1) curb excessive dependence of external resources (to enhance the accumulation of expertise); 2) enable/enhance cross-organizational learning cycle to accumulate experience that can be used for new products. If you're interested in the topic but are stuck at the paywall, the concept of organizational capabilities is also detailed in Kenichi Kuwashima's 1999 paper found here.

[Blog post] My colleagues Simin Takidar and Bipasha Das published a blog post on Taking a Proactive, Preventive Approach to Data Privacy in Clinical Documentation. It's an challenging topic and relevant to protocol development in that it forms part of the critical path between study design and submission. Unlike other clinical documents, like CSRs for example, redactable content in protocols is mainly company confidential information (CCI) and little personal protected data (PPD). Nevertheless, study teams shouldn’t be complacent in their efforts to prepare for redaction, otherwise it can trip up submission timelines.

Education Corner

[Blog post] Protocol authors in industry are typically medical writers. In that vein, AMWA's latest blog post on Medical Writing: A Professional’s Guide to Advancing Your Career might be an interesting read for many readers. The post covers topics ranging from building your value, soft skills, core knowledge, technology and writing and editing mechanics. In my experience in regulatory medical writing - and for protocols in particular - the soft skills and clinical trial design sections stood out.

[Article - Review] Unless you specialize in oncology it's likely that oncology protocols appear to be a sea of abbreviations occasionally strung together with a word in-between. Niu et al recently published an article on Signaling pathways and targeted therapies in lung squamous cell carcinoma: mechanisms and clinical trials where they provide a great orientation resource for anyone looking to break into LSCC (or who have had the misfortune of being assigned to a protocol without any preparation material).

Webinars

Sanofi and IQVIA are hosting a webinar on Sanofi Reshapes Patient Experience With Digital Technologies on Wednesday 26 October 2022 19:00 -20:00 CEST where Sanofi will discuss the new R&D model that sees 100% of its development programs informed by patient communities and 100% of Phase 2/3 studies having a remote capability built into them.

TransCelerate are hosting a webinar on Digital Data Flow (DDF): Connectathon Results and Outcomes on Tuesday 1 November 2022 17:00-18:00 CEST where they will provide an overview of the connectathon results and outcomes.