Clinical research is a collaborative process, involving close cooperation between patients, sponsors, sites, and CROs. If we are interested in improving clinical trials, we need a clear overview of how these moving parts interact with each other. That’s why, in this episode of the Research Confidential podcast, ProofPilot Chief Strategy Officer, Joe Kim, spoke with Adrienne Gaggi, Associate Director of Clinical Development at Aldeyra Therapeutics, whose combined experience of working in sites, at a CRO, and for pharma and biotech sponsors gives her a unique perspective to offer.
Career path sparked by a childhood passion
Adrienne has had a passion for developing new medicines and helping others since childhood, and that has driven her along the path to becoming a clinical research professional. Starting off as a CRA, Adrienne worked her way up through roles as a study coordinator, and later a manager of a study site, then into a CRO - including a stint in a CRO in China - before moving to the sponsor side. Her early roles were in larger pharmaceutical companies, before transferring to Aldeyra Therapeutics, the small Boston-based biotech firm where she is responsible for planning and designing all clinical trials across the multiple programs in their pipeline.
Joe opened the podcast up by asking Adrienne what was most surprising during her time at a site, and the answer was the lack of patient education about their medications. Patients coming into a pharmacy to collect their medications without even knowing the name of their drug, what it is for, or the kinds of interactions their drug may have, all highlighted to Adrienne the importance of patient education and the need to inform the public more about what goes on in clinical trials. This is an eye-opening insight for those who focus on patient recruitment and pre-screeners or call centers to assess the fit of potential patients. Patients who may misremember their medications create more burden and cost for themselves, sites, and sponsors when screening for trials. ProofPilot aims to improve this with a novel EMR record-sharing feature in its platform.
The delicate art of enrollment estimates
Adrienne then gave some insight into the complexities and challenges faced when selecting sites for a study. Typically - if working with a CRO - a sponsor may be given a list of potential sites to choose from. The sponsor must then decide on which sites to select, and on how many sites in total to use in the study, based on performance and suitability metrics (e.g., recruitment rate, experience within certain therapeutic areas, history of major deviations, and PI’s years of experience) provided by the sites. The issue is, sites often inflate their own figures to suggest greater recruitment capability than they actually have, making it difficult for sponsors to make accurate estimates of study enrollment and so sponsors in turn, discount that estimate, creating an unproductive wager around the final, realistic estimate.
The solution? Adrienne favors an upfront approach with sites, letting them know that quoting a smaller, but more reliable number of patients is more valuable and appreciated. Adrienne also acknowledges that sponsors should take some responsibility for providing more detailed study information to potential sites - rather than just the bare bones of a protocol synopsis - to enable more accurate enrollment forecasting, resourcing, and budgeting by sites.
The challenge is sponsors will often not have a complete protocol ready to offer sites by the time they start the site selection process. So, Adrienne goes back to the importance of being open and honest in interactions between sites and sponsors - including, for example, a site admitting they don’t know how many patients of a certain type they will be able to enroll - to allow study planning to at least take into account the unknowns.
Joe probed further to understand how sponsors can help sites meet enrollment targets. Adrienne felt that there are still opportunities to be had by opening up inclusion and exclusion criteria as much as possible - whilst still maintaining data integrity and patient safety. Many studies often use preexisting templates of I & E criteria, or include ‘default’ criteria - such as no HIV positivity, or no cancer in the last five years. Adrienne often questions if these criteria are really justified for a particular study and if some of them can often be removed.
Decentralized Clinical Trials: The future of clinical research?
Moving onto decentralized trials, Joe brought up a question about DCTs that Adrienne had recently posed on her social media. Namely, “are DCTs really the future, or are they just an idea hyped up by tech companies trying to sell their technology?” Adrienne described how despite DCTs being talked about a lot at meetings, conferences, and on industry social media, no one she encounters seems to talk about them during their day-to-day work ‘on the ground’ in clinical research.
Adrienne added that she thought the name ‘decentralized’ clinical trials also made little sense to her as, by pushing to streamline all the different systems (e.g. EDC, e-Consent, and wearables) into one platform, tech providers are essential, centralizing the data. Adrienne did concede that the practical aspect of having all systems under one login (as opposed to needing a spreadsheet just to keep track of your usernames for various systems) however, would undoubtedly be a major benefit.
Another hard truth about DCTs for the industry that Adrienne brought up is that technology providers are pushing sites to adopt their DCT-enabling platforms, yet this also inevitably pushes clinical research towards a future with less need for sites, and therefore less need for site staff, which may backfire in the long run.
Opportunities and challenges in DCT implementation
Exploring DCT challenges further, Joe wanted Adrienne’s take on the challenge of oversight of DCTs, asking how trials could be adequately monitored and managed if procedures were being done at home or in pharmacies, and not in the presence of the PI or any study staff.
“Sometimes I have issues with my PI even logging into a portal to do training at the start of a study. Are they going to be comfortable signing off on data for a patient they have never met?... I don’t know”
Adrienne felt that oversight of DCTs in disease areas that require more complex procedures would be difficult, and therefore patients in oncology, asthma, or COPD studies, which require biopsies, pulmonary function tests, or other complex assessments, will still need to come on-site for the foreseeable future. However, she did see a DCT approach working in other formats and therapeutic areas, like mental health, where more data can be collected via questionnaires and wearable devices. Adrienne believes a hybrid approach, based on the study format and therapeutic area, seems the most appropriate for now.
One point that Adrienne felt is often missed in the march towards DCT adoption is how, for many trial participants, getting extended attention from a PI (versus the typical 15 minutes with a general physician), and spending time with study staff is their favorite part of a trial. With all that patient-healthcare professional interaction at risk of being removed, or at least reduced in DCTs, researchers need to consider the impact this has on the patient experience, and potentially on recruitment.
Ultimately, Adrienne did not class herself as a complete skeptic on decentralized clinical trials, but she did feel that she would rather wait another couple of years until more of the technologies and practices have been tested and proven to be capable of generating high-quality data. And given the recent events with Pfizer and Care Access, this caveat certainly rings true.
Being grateful for - and investing in - what we already have
One final point Adrienne made is that there are still gains to be made in the current site-based, or even hybrid model, by investing more in patient-centricity and improving the patient experience. For example, by having adequate travel reimbursement for patients, by updating stipend amounts to align with today’s cost of living, and by paying sites enough so they can deliver a patient-centric experience in their studies, sponsors will see returns in the form of higher rates of recruitment and better patient retention in trials.