I think it’s fair to say that the Pharma R&D world is hypnotised by Decentralised Clinical Trials (DCT) at the moment. While it’s challenging to define DCT, it can be described as trials that are carried out through telemedicine and mobile or local healthcare providers, leveraging processes and technologies that are different to the traditional clinical trial model which is heavily focussed around the ‘site’ (the specific hospital or clinic selected by a pharmaceutical (Pharma) company or Contract Research Organisation (CRO)). For me and many of my peers, DCT represents providing more possibilities and options for people participating in clinical trials. While DCT isn’t a new concept, the forced acceleration of decentralisation of clinical trials during the pandemic has presented plenty of opportunity for a makeover of many of our existing processes, and fortunately site feasibility has also undergone a reformation.
For many years site feasibility (the process of assessing the possibility of running a particular clinical trial at a specific hospital or clinic (the ‘site’) has maintained persistent challenges. By definition, Site Feasibility is the evaluation of clinical trial sites by a Pharma company or CRO. The objective is to determine their ability to accomplish certain clinical study success criteria; specifically, conducting and completing the trial within budget and timelines, achieving patient recruitment targets, and generating high quality data. As an industry we’ve endured endless discussions about the problems, perils and perfunctory nature of existing site feasibility processes. From the Pharma/CRO perspective, processes are stagnant and inefficient, and predicting site performance and mitigating site-related risks to study conduct has been consistently difficult. For the sites, the processes and methods bestowed on them by Pharma/CROs are still burdensome, outdated and assume that ‘one size fits all’, neglecting the fact that their closeness to patients means they require options and flexibility. All of this has led to disappointing metrics that have barely changed over the years: 37% of sites under enrol patients, 11% of sites fail to enrol a single patient, and of 89% sites will reach enrolment targets only once the study timelines have doubled. As a result, approximately 80% of clinical trials are delayed due to poor patient recruitment. Ineffective and unproductive site feasibility processes have a significant influence on these numbers.
Working in this space over the years, I have explored different practices, strategies and solutions to solve the site feasibility puzzle, working with and within companies to attempt to redefine the process before realising that the industry’s approach towards site selection has made these challenges somewhat systemic, thus requiring a complete overhaul. More importantly, an overhaul that needs to go back to what or should I say who is at the heart of the trial…the patients.
During the pandemic, patients’ willingness to go to central clinics for treatment or monitoring declined significantly with a heightened fear of COVID infection. This was one of the primary reasons for many companies shifting their clinical trial delivery model from being centred around the clinic to be more patient-focused. With this development, the Key Performance Indicators that our industry measures itself to are evolving, and the experience and perception of the patient is becoming a critical performance measurement that directly impacts the evaluation and selection of clinical trial sites.
Let’s talk site feasibility surveys! A site feasibility survey or questionnaire is a set of questions prepared by study teams (at Pharma or CRO company) asked to staff at clinical trial sites to determine their interest and suitability for a particular study. Feasibility survey questions primarily focus on site facilities and infrastructure, site staff experience and availability, and whether the staff have been adequately trained. Questions about perceived regulatory challenges and site start-up timelines are also standard. For most of us, the most critical aspects of the feasibility assessment are the questions that appraise a site’s engagement with patients. Typically, the questions around patients have an emphasis on the number of appropriate patients in a site's database and how many they estimate they can recruit from that pool. I don’t think we have paid enough attention to many other crucial considerations of the site-patient rapport and the overall patient experience.
While it seems obvious to simply ask better questions, most companies have continued with their existing site feasibility style, however ungainly or unsatisfactory, until the acceleration of decentralised clinical trials! The COVID pandemic-driven-quickening of moving from “site-centric” trials to “patient-centric” trials has given us the opportunity to do a complete renovation of the box-ticking, cursory-style questioning and reimagine site feasibility surveys through a patient-centric lens. So, how is this being done? Well, it starts with adding depth to inquiries about the site’s access to patients and whether they have the infrastructure to support and enhance their trial experience. Of course, number of patients within a clinic’s database and the site facilities is important information, but that information becomes more useful when it is framed with an understanding of the site-patient relationship, a couple of examples are:
How broad is the patient population that the site has access to?
With the rise of decentralised trials, there is an opportunity for Pharma companies to achieve more diverse recruitment and reach broader geographies. Consequently, ascertaining a site’s ability to access a wider range of patients, even those that do not live in close proximity to the site location, is now a necessary assessment. With this, we have to understand whether the site has the appropriate digital capabilities and readiness to support and maintain an expanded patient and healthcare provider network.
Does the site have capability/experience with supporting diverse patients?
Clinical trial diversity goes beyond access to diverse populations - it includes the ability to adequately support the needs of different patient populations, in order to engage and retain them on a trial. Recent data has shown that some of the top-rated hospitals in the United States are falling short with respect to racial inclusion and diversity. I also recently read about a study in Europe that revealed there hasn’t been enough focus on the training needs of healthcare workers serving the LGBTQ+ community. It’s widely known that a significant barrier to trial participation for diverse populations is their lack of trust in healthcare and Pharma companies. As a black African in the UK, discussions with family and friends from similar backgrounds about their experiences with healthcare services has highlighted a lack of cultural awareness and sensitivity from healthcare professionals. This experience is amplified in clinical trials where there is heightened cautiousness from potential trial participants. It therefore becomes a necessity to determine whether site staff have received adequate training to support inclusive and diverse patient populations.
In addition to understanding the site-patient relationship, it’s important to ask the site more contextual information about patients that could inform the study execution strategy:
What information does the site have about patients and technology adoption?
Technology accessibility and proficiency of patients within a site’s database is being queried more (largely driven by the pandemic, as this is a critical implication to decentralised trial strategies). The sites that have the ability to track whether patients have smartphones, or provide insight into the proportion of patients who are comfortable using technology can indicate how likely or easy it is for patients to participate in virtual visits or use digital applications for consent or Patient Reported Outcomes.
Is the Pharma company’s protocol design executable from the site’s viewpoint?
In clinical development, a clinical trial protocol is a document describing how a clinical trial will be conducted including the study purpose, design, methodology, statistical considerations and organisation of the trial. Strangely, feasibility surveys have more content asking sites whether they have a -70-degree freezer instead of whether they think the protocol design is viable from their perspective and experience with patients. Additionally, many organisations still wait until they have developed their final protocol before planning for feasibility and obtaining the site’s input. Designing a protocol and identifying and selecting the right sites should run in parallel. For example, it’s necessary that Pharma companies and sites (and patients of course) collaboratively develop and assess the practicality and achievability of the patient inclusion and exclusion criteria, to make sure protocol complexity and patient burden is minimised where possible, ultimately boosting patient recruitment and enablement.
In summary, decentralised clinical trials have highlighted the need to move away from the industry status quo with haste and innovate faster. It’s great to see some of that quickened innovation being realised in the site feasibility process by recognising that the data obtained from site feasibility requires more depth around the patient experience. As I said in my blog post What’s More Personal Than Health?: “We all love data, but true patient centricity recognises the need to make data more about the person”. This attitude very much applies to site feasibility and selection. Although we’re all entranced by decentralised trials at the moment, our next steps should be to explore more strategies to reform site feasibility beyond what’s needed for decentralised trials. Our mission should be to continue removing wasteful steps and stop collecting non-critical data, but rather focus on optimising site feasibility in a patient-centric manner, to improve patient access to clinical trials and speed to new treatments.
References:
Clinical Trials Transformation Initiative. CTTI Recommendations: Decentralized Clinical Trials. CTTI White Paper. 2018. Available at: https://www.ctti-clinicaltrials.org/sites/www.ctti-clinicaltrials.org/files/dct_recommendations_final.pdf. Accessed June 3, 2021.
TRIALFACTS. Data Doesn’t Lie: Clinical Trials Enrollment Forecasting – Is It Worth It?. Trialfacts.com. 2018. Available at: https://trialfacts.com/data-doesnt-lie-part-l-clinical-trials-enrollment-forecasting-worth-it/. Accessed June 1, 2021.
Willis, R.C. Special Report on Clinical Trials: Delving into decentralization. Drug Discovery News. 2021. Available at: https://www.drugdiscoverynews.com/special-report-on-clinical-trials-delving-into-decentralization-15044. Accessed June 1, 2021.
Nuer, A. Revamping Site Feasibility as Trials Become Decentralized. Applied Clinical Trials. 2021. Available at: https://www.appliedclinicaltrialsonline.com/view/revamping-site-feasibility-as-trials-become-decentralized?utm_campaign=2021_GL_LI_SLTThoughtLeadership&utm_content=163978343&utm_medium=social&utm_source=twitter&hss_channel=tw-1199818892. Accessed June 1, 2021.
Heath, Sara. Top-Rated Hospitals Fall Short in Racial Inclusivity, Health Equity. Patient Engagement HIT. 2021. Available at: https://patientengagementhit.com/news/top-rated-hospitals-fall-short-in-racial-inclusivity-health-equity?eid=CXTEL000000604950&elqCampaignId=19400&utm_source=nl&utm_medium=email&utm_campaign=newsletter&elqTrackId=ca57b6c0317448fdbd445185b2c45143&elq=aedeed87803f4812b5138b775da42337&elqaid=20225&elqat=1&elqCampaignId=19400. Accessed June 1, 2021.
Ford, M. Europe’s nurses need more training to ‘reduce biases’ around LGBT+ issues. Nursing Times. 2021. Available at: https://www.nursingtimes.net/news/research-and-innovation/europes-nurses-need-more-training-to-reduce-biases-around-lgbt-issues-03-03-2021/. Accessed June 2, 2021.
University of California San Francisco. Clinical Trial Protocol Development. Clinical Research Resource HUB. 2017. Available at: https://hub.ucsf.edu/protocol-development#:~:text=The%20protocol%20is%20a%20document,integrity%20of%20the%20data%20collected. Accessed June 3, 2021.
Miesta, E. Bayer Overhauls Its Clinical Trial Planning Process. Clinical Leader. 2020. Available at: https://www.clinicalleader.com/doc/bayer-overhauls-its-clinical-trial-planning-process-0001. Accessed June 1, 2021.
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