Travel restrictions, stay-in-place orders, safety concerns and other factors have caused interruptions and cancellations of many clinical trials. Hitting the ‘pause’ or ‘stop’ buttons on clinical research projects can be costly, and they prevent potentially life-saving therapies from getting to market in a timely manner.
In order to avoid such harmful interruptions, sites and sponsors may need to implement changes to ensure continuity. Outsourcing-Pharma (OSP) spoke with Gen Li (GL), founder and president of Phesi, about how the pandemic has impacted trials around the globe, and how trial teams can work to keep their vital work going.
OSP: Could you please talk about some of the general ways COVID-19 has impacted trials?
GL: The pandemic has had a huge impact on trials infrastructure – many staff have been furloughed, and many labs and research institutions closed, even if only temporarily. At the same time, travel restrictions remain in place and participants are naturally worried about interacting in-person with healthcare professionals.
The effect of social distancing and the need to shield vulnerable patients has led many sites to be suspended. Now, as the immediate crisis transitions into a semi-permanent state, biopharmaceutical companies and sponsors need to take steps to work around COVID-19; this means keeping trials going by continuing to fund them, even when they are suspended.
The virus is rightfully dominating current agendas as the search goes on for a vaccine, but there are other, vital R&D projects – some many years in the making – that must be protected. We are seeing efforts by biopharmaceutical companies to make sure this is case; this includes reviewing their operating models and particularly the options around technology solutions; For example, digital solutions can facilitate meetings between patients and healthcare practitioners and help to overcome the physical barriers in place.
OSP: Phesi recently analyzed comprehensive trial site data – could you please tell me about some of the things you discovered, and what the numbers might mean for the trial industry?
GL:Our analysis of more than 300,000 global sites found a 38% increase in site suspensions since the start of the year, coinciding with the onset of several international ‘shutdowns.’ This is concerning because it costs a minimum of $30,000 to (re)activate a site and takes an average of 100 days for an investigator site to be operational.
Moreover, if we look ‘behind’ the headline figure of suspended sites, further problems emerge. There is no doubt many suspensions are the result of the pandemic, but our analysis also found many trials were destined for failure, even if COVID-19 had never happened.
One of the most common reasons for failure is poor protocol design, which is the main driver of slow patient enrollment currently being disguised as impact from COVID-19. Other reasons include poorly executed site activation, and competition.
OSP: What are some of the dangers in suspending a trial?
GL: There are implications for all a trial’s stakeholders. Firstly, for patients as participants, particularly for those with underlying health conditions, it’s an extremely uncertain time and disruption to their treatment regime will only compound the worry.
Secondly, for independent trial sites, even a short-lived temporary shutdown could spell permanent closure, as they continue to rack up infrastructure costs without any revenue coming in. Thirdly, for the sponsor, mounting costs and the time it takes to open new sites are both issues.
There’s also the serious knock-on effect of the quality of the study through loss of patient data or trial results – it is unclear what additional package approval challenges this data discontinuity will cause in the future.
OSP: How does competition (for patients, and other resources) come into play?
GL: Competition between sites and studies is certainly a factor, also being masked by COVID-19. For example, another analysis we carried out found the number of recruiting sites for Crohn’s disease, which has a limited patient population, increased in the three years before COVID-19 from under 2,000 to more than 9,000; the analysis data also show poor country allocation and site selection for several of the leading trials that are running.
This problem wasn’t created by the pandemic, but the reality is that some of these programs will inevitably be terminated so that the focus can be placed on those trials with the best chance of succeeding. Also, without an understanding of the data, it is possible that when development restarts, without predictive analysis and evaluation, the trials chosen for ‘resurrection’ will actually be those ‘zombie’ trials most likely to fail.
OSP: How can sites better overcome all these obstacles?
GL: It comes down to having a clearer understanding of the trial landscape and taking a data-led approach. Around a fifth of trials will fail, even without COVID-19 in the picture; a deeper analysis of available data enables sponsors to identify all the variables associated with their study and mitigate the risk of failure.
Moreover, almost all phase two and three trials will undergo one or more protocol amendments, so sponsors may also wish to take advantage of the current slowdown in trials to refine the design of their existing studies now using available data.
One other aspect to avoiding common pitfalls, and it’s one I believe will be a fundamental part of any successful clinical development portfolio post-COVID-19, is how sponsors use real-world patient data. For instance, although synthetic control arms are currently ‘fashionable’– by using real-world data and evidence collected from patients, we can reduce or even eliminate the need to expose patients to a placebo or comparator arm.
Ultimately, analytics has a very strong role to play in improving trials and is an essential part of the toolkit when it comes to overcoming obstacles.
OSP: What is a “data-driven” approach?
GL: Data-driven approaches are those led by the data to inform and optimize trial design and execution, and involve a systematic analysis of the clinical trial, clinical protocol, and clinical site space to identify what is most likely to work. An analysis of the clinical site environment for a therapeutic area – including geographical location, existing studies, and patient population – allows a sponsor to build a better protocol with a higher chance of a positive outcome.
Real-world data from current and completed studies are key, as is continuing to evaluate and track site performance to make real-time adjustments based on data. This data-driven approach helps sponsors design much smarter trials and improves the chance of a clinical trial with a successful outcome.
OSP: What are the benefits of a trial becoming more data focused?
GL: The biggest benefit will be getting therapies to patients faster. COVID-19 has caused significant global disruption, but it has also brought the industry to a turning point by highlighting the existing problems with trial design and execution.
Addressing these problems now by taking a data-driven approach will have a long-lasting, positive impact on drug development and commercialization – reducing the cost of trials and increasing the chances of successfully bringing a drug to market. Those companies who make the switch to become data-driven will better navigate the challenges ahead and will in fact emerge stronger.