By Ed Miseta, Chief Editor, Clinical Leader
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As COVID-19 continues to wreak havoc on companies and economies around the world, the life sciences industry is finding it, too, has not been spared its wrath. Eli Lilly and Company has already announced plans to delay most new clinical trial starts and pause enrollment for most ongoing studies. The FDA has also announced guidance for companies conducting trials during the pandemic, which focuses on patient safety, protocol modifications, virtual visits, missed visits, and COVID-19 screening procedures.
Still, the impact of the pandemic on clinical trials will be significant. In fact, a recent note from GlobalData shines a light on the impact COVID-19 will have on clinical trials. GlobalData interviewed 10 trial experts who noted the pandemic is already extensively impacting studies. The experts now expect clinical trials will likely sputter from enrollment and patient care through to data collection and analysis.
No area of trials is safe at this point. GlobalData notes trials will suffer irrespective of indication. The impact is expected to be felt for months to come. According to statistics website Worldometer, the COVID-19 virus has thus far resulted in close to 400,000 confirmed cases and over 17,000 deaths.
GlobalData reached out to several oncologists, specialists, and investigators from the U.S., Europe, and Australia to discuss preparedness programs in their clinics and how care for patients has been altered. Trial recruitment is likely to slow due to curtailed patient visits to the hospital. Reallocated resources for clinical trial management will also mean health volunteer recruitment for Phase 1 trials will also take a significant hit. Immunotherapy and chemotherapy schedules are being altered, as are follow-up and screening schedules.
Expect Enrollment To Slow
Prior to the emergence of Covid-19, patient enrollment was one of the more difficult aspects of trial start-up. That task will now be made even more difficult. One British oncologist noted COVID-19 preparedness programs are taking precedence over non-urgent activities. This would include recruitment for clinical trials. With significant resources being diverted to quell the pandemic, capabilities are being stretched. In some cities, the healthcare system is being taxed and approaching a crisis level.
To make matters worse, even clinicians are being forced to work from home to avoid exposure to the virus. For example, Dr. Leonard Saltz, a medical oncologist at Memorial Sloan Kettering Cancer Center in New York is working from home four days a week, as five employees and three patients at the center have tested positive for COVID-19. Saltz expects a three-month delay in trial operations as a best case scenario. No one knows exactly what to expect beyond that assessment since there is no precedent for this situation which continues to change daily.
The FDA and NIH have both issued guidelines pertaining to the conduct of trials during the pandemic. While pharma companies will focus on the FDA guidelines, those issued by the NIH cannot be overlooked. As noted in the GlobalData report, many studies today are conducted at research centers that have a mix of public and private funding. Those centers need to be compliant with NIH guidelines.
Dr. Sami Hoque, a consultant gastroenterologist at Barts Health NHS Trust at Whipps Cross University Hospital in London notes other activities are taking precedence. He has already stopped screening patients for trials.
GlobalData expects the extent of the impact on enrollment to depend on the nature of the study. A trial that requires multiple patient follow-up visits to a clinic will likely be more harshly impacted by the virus than a study with infrequent visits.
Data Will Be Impacted
Patients and clinics cancelling or delaying visits will hamper data collection. The experts GlobalData spoke to expect a long-term impact on data collection for ongoing studies. They believe the lack of widespread COVID-19 testing for patients may also confound the eventual results.
The impact of COVID-19 on clinics will also cause investigators to reexamine their methods. The website of U.S.-based investigator-led consortium NRG Oncology is encouraging investigators to explore alternative methods of obtaining data. Those methods could include study visits conducted by phone or videoconferencing. Guidance on the site also informs investigators that alternative procedures which do not impact patient safety, compromise the overall integrity of study data, or affect the willingness of patients to participate in the trial would be considered minor protocol deviations.
Those deviations would need to be documented in the medical record by the investigator with the reason for the deviation and justification for why it was considered to be minor. In those cases, the protocol deviations only need to be reported to the organization leading the trial. The FDA’s guidance recommends that sponsor companies consult with IRBs and IECs when deviations from protocols are deemed necessary.
Additional Covid-19 Concerns
Unfortunately, there are even more concerns for sponsor companies and clinics. One is the number of patients participating in a study who may have COVID-19 but be asymptomatic. There are also hospitals currently limiting non-essential visits, which will have an impact on clinical trial monitoring. That drop in visits will also impact data collection, data cleanup, and auditing. Companies will also need to accommodate patients who no longer feel safe visiting a hospital or clinic.
Finally, the virus itself may impact study results. The size of some studies may not be large enough to accommodate large numbers of patients who are sick due to COVID-19. Joel Wallace, IP partner at Schiff Harden, notes things could get complicated from a regulatory and data integrity point of view.
Patients infected with COVID-19 will impact standard assumptions made in the study design, such as risk of mortality in a geriatric study. Data will now have to be more carefully scrutinized, especially with respect to pulmonary side-effects. According to one doctor from MD Anderson, even if the pandemic does not factor into the outcomes of trials, it will certainly muddy the efficacy data.