How is COVID-19 impacting clinical trials?

With healthcare resources being diverted to deal with the pandemic, patients unwilling or unable to go to trial sites, and concerns about potential pharmaceutical supply chain disruption growing, most companies are unable to continue normal conduct of trials and site-based studies. The situation continues to change daily, but thus far some leading pharmaceutical companies have stepped forward to address how they are handling clinical trial difficulties, at least in the short-term, in the face of COVID-19:

Broadly speaking, the initial response has been to delay initiation of new trials, and in many cases to pause recruitment of new patients to ongoing studies. The picture is murkier for patients already enrolled in ongoing studies, but many will face disruption. Most corporate guidance issued to date covers the next four to six weeks, but with significant disruption from the pandemic expected through the summer at least, further clinical development decisions can be expected in coming weeks.

The FDA and EMA have both published initial guidance for drug-makers on conducting clinical trials during the COVID-19 pandemic, with patient safety at the forefront of all considerations. Specific measures include the conversion of physical patient visits into virtual visits and offering additional safety monitoring options for patients who can no longer access the investigational product or trial site. The FDA and EMA both acknowledge that clinical trial protocol modifications are likely to occur as trials continue to be adversely affected by COVID-19 in the coming weeks and months, though it is not clear how such considerations might affect future review in regulatory filings.

Apart from the general guidance offered by the FDA and the EMA, several medical professional associations such as the American Society of Clinical Oncology (ASCO), the European Society for Medical Oncology (ESMO), and the National Comprehensive Cancer Network (NCCN) have all provided resources informing members as to the appropriate conduct of clinical study during the pandemic. These recommendations largely echo those set forth by regulatory agencies but also provide important context relevant to specific disease areas and include recommendations on restricting non-urgent diagnostic and screening tests, conducting patient safety follow-up visits by phone, and coordinating with study sponsors to arrange for research medications to be sent directly to subjects if feasible.

In addition to the recommendations of medical societies, individual hospitals, academic centres, and community practices have also implemented their own individual clinical care guidelines, each offering distinct patient screening and testing protocols, policies and procedures, and administrative and clinician tools. The common refrain across institutions is restriction of enrollment in clinical studies to those that are most likely to benefit patients. The extent to which clinical studies will ultimately be prioritized as the burden of the pandemic on the healthcare system increases is still to be seen, however we expect potential sites to become much more selective over trial participation in the short to medium term.

We expect most pharma companies to refrain from initiating new trials over the coming weeks, however with health officials expecting multiple waves of disruption over the next 18-24 months it is likely that many companies will develop more nuanced contingency plans. Some programmes will inevitably be side-lined as a result of the pandemic, either by strategic choice or due to greater selectivity on the part of functioning trial sites, but many more will adapt planned and ongoing studies within the new realities of the pandemic. This may prompt more companies to re-evaluate the risk reward analysis of shaking up established clinical trial practices, including greater use of a real-world comparator in trial design and the use of innovative approaches to getting trial drugs to patients, remote monitoring and the use of telemedicine in trials.

Disruption-driven innovation may ultimately provide lasting benefits for the industry, though it inherently comes with risk for those attempting to navigate a rapidly changing landscape. Whether the result of active decision-making to adapt to the crisis or unforeseen future disruption, many clinical programmes can expect their final data package to be affected. Whilst the FDA and EMA have signalled some understanding that protocols will need to change, it is unclear how future regulatory and payer assessments will accommodate these differences.

References

1. https://investor.lilly.com/news-releases/news-release-details/lilly-provides-update-clinical-trial-activities-during-covid-19
2. https://www.fiercebiotech.com/biotech/covid-19-prompts-pfizer-to-stop-enrollment-most-studies
3. https://www.biospace.com/article/merck-bms-pfizer-and-others-pause-enrollment-in-some-clinical-trials-due-to-covid-19/
4. https://www.aasld.org/about-aasld/covid-19-resources
5. https://www.hematology.org/covid-19
6. https://www.asco.org/asco-coronavirus-information
7. https://www.esmo.org/newsroom/covid-19-and-cancer
8. https://jnccn.org/view/journals/jnccn/aop/article-10.6004-jnccn.2020.7560/article-10.6004-jnccn.2020.7560.xml