If you missed our live panel discussion on how the drug development industry is being impacted by the COVID-19 pandemic, we have assembled this post to highlight some of the key takeaways. Our panel included five industry experts, each with at least 20 years in the drug development industry, answering audience questions and providing their unique perspectives on how the current pandemic is shaping the future of drug development around the world.
What are the Most Immediate Pandemic Impacts in the Pharma/Biotech Industry?
Clinical Trials on Hold
The COVID-19 pandemic has impacted all phases of drug development and forced many drug development companies and clinical research organizations (CROs) to put at least some – and in many cases all – of their clinical studies on hold. While pausing clinical studies is not uncommon (especially early in development), never have so many companies simultaneously experienced a disruption of this magnitude. Despite this, Sponsors of paused studies are still finding ways to progress their programs by taking proactive steps to ensure their studies are ready to move forward when conditions improve (more on this later).
New Reality for Ongoing Studies
For those studies that have remained open, the new reality of government-mandated stay-at-home orders, social distancing, and widespread anxiety over potential COVID-19 exposure has led to many challenges. These challenges relate to fundamental study elements such as subject recruitment, clinical site access, in-person clinical assessments (e.g., blood draws), and ensuring subjects have access to study drug. Even as the stay-at-home orders are relaxed and life returns to a more normal state, these challenges are likely to continue in some form. As such, Sponsors may need to consider less traditional study design approaches to overcome them.
Study Assessment Challenges
One of the biggest challenges for ongoing studies is finding ways to ensure the timely completion of clinical assessments that have traditionally been performed at the clinical site. While it is possible to have subjects document some vital signs themselves using commonly available home-health equipment (e.g., thermometers and blood pressure cuffs), blood draws are almost always performed by a healthcare professional. These blood samples are critical for pharmacokinetics, laboratory assessments, and other key endpoints.
Some Sponsors are overcoming this logistical hurdle by providing subjects with at-home finger prick capillary blood kits. Using these kits, subjects can take samples at specified timepoints and either mail the dried blood samples to the Sponsor or bioanalytical lab for analysis or retain the samples at their homes until they can visit the trial site again. However, this option is not appropriate for all programs, including those that require larger volumes of blood for analysis, and should be evaluated on a case-by-case basis.
When remote options for blood sampling are not appropriate, it may be possible to limit the number of in-person visits to the clinical site while still collecting enough samples to allow for a robust analysis. In such cases, modeling and simulation approaches can prove vital for answering key questions about your drug.
As usual, if fundamental changes to the study protocol such as new sampling approaches are instituted, appropriate protocol amendments must be submitted and approved by the institutional review board (IRB) or similar entity, and relevant regulatory authorities should be notified.
Ensuring Access to Study Drug
In addition to testing challenges, the logistics of getting experimental drugs to subjects has required some rethinking. This has historically not been an issue, as study subjects would simply receive the study drug as part of their scheduled clinical visits. Now, rather than having subjects come to the study site to pick up their trial materials, some Sponsors have opted to ship study materials directly to study participants. While this can be a viable approach, Sponsors must ensure that subjects can safely self-administer the treatment and that the drug is stable enough for shipment and storage at a subject’s home without detrimentally affecting safety or effectiveness. Furthermore, a mechanism for maintaining drug accountability and adequate documentation must be implemented.
For drug types that might not be suitable for self-administration (e.g., infused drugs or those requiring special safety monitoring), alternative approaches may be needed. For example, it may be possible to have clinical staff visit the subject’s home to administer the drug or to utilize a clinical site with less potential exposure to COVID-19 (e.g., choosing a Phase 1 unit versus a hospital or primary care clinic).
As with adjustments to study assessments, any new approaches to drug administration must be included as a formal protocol amendment submitted to the IRB and appropriate regulatory authority.
Will Phase 1 and Phase 2–3 Studies Experience Similar Impacts?
Studies will be impacted in different ways based on the nature of the studies and the sites that support them. A lot of this has to do with the benefit-risk assessment. For example, some Phase 2 or 3 studies may not be paused when patients are seeing a clear therapeutic benefit from an experimental drug. In these cases, Sponsors, with input from medical monitors, may be able to implement protocol modifications that allow the trial to continue in a way that sustains these positive therapeutic effects while maintaining patient safety.
Most Phase 1 studies are conducted in healthy volunteers to assess the pharmacokinetics and/or safety profile of a drug. Unlike Phase 2 or Phase 3 studies, there is typically no direct benefit to subjects participating in Phase 1 studies. As such, Phase 1 studies are more likely to be paused since the risk of coronavirus transmission is not outweighed by potential therapeutic benefits. This balance will likely evolve as testing procedures for the coronavirus become more available and as sites develop strategies to minimize risks to study participants. For Sponsors, it is critical to maintain close contact with study sites to understand the processes that they are implementing to minimize risk.
Staff availability can also differ between Phase 1 study sites and Phase 2 and 3 sites. Many Phase 1 units have dedicated staff that are not necessarily involved in primary patient care, so they may be more available to continue study activities during the pandemic. Phase 2/3 sites are typically hospitals, medical centers, or other sites of direct patient care. These sites may be focusing their staffing resources toward the care of COVID-19 patients, especially in areas with large numbers of cases. It is important to consider that even in Phase 1 units, some medical staff may decide to help with COVID-19 outbreaks, thereby limiting their availability to conduct Phase 1 studies.
What are the Long-term Impacts of the COVID-19 Pandemic on Clinical Trials?
The degree to which the COVID-19 pandemic shapes clinical trials over the long term will likely depend upon how long the pandemic lasts. For studies that initiated prior to the outbreak, the longer it takes to reopen, the less likely it becomes that previously enrolled subjects will return to the study. This may require additional rounds of subject recruitment once these trials resume to replace subjects who have been lost. In addition, drug stability may become an issue in these trials. As stocks of experimental drugs sit idly in storage, it is likely that many will pass their established expiration dates. To overcome this, Sponsors may need to conduct additional stability testing to extend the expiration dates or may ultimately need to manufacture and test new drug batches.
While the added time and expense of addressing pandemic-related issues in clinical trials is an obvious hurdle, there could also be some silver linings for how clinical trials are conducted moving forward. Many of these relate to virtual drug development. Clinical trial Sponsors and clinicians have been increasingly adaptable in conducting virtual study visits with participants and acquiring study data remotely. Furthermore, wearable devices are being deployed to aid in remote monitoring of vital signs, and mobile apps are quickly replacing pen-and-paper study logs. These technologies have become increasingly relevant during this pandemic as Sponsors evaluate methods to minimize face-to-face interactions with study participants. As more Sponsors implement these new approaches, it seems likely that we will begin to recognize them as standard study elements that will remain with us long after the pandemic has faded.
How Will Nonclinical Studies be Impacted?
Since nonclinical studies do not typically involve as much human-to-human contact, the impact on nonclinical work is expected to be less than on clinical studies. However, nonclinical sites will still likely feel some of the burdens of the pandemic, especially with stay-at-home orders limiting the ability of laboratory staff to perform their duties and the potential for disrupted supply chains. Other challenges include the potential need to store study samples for extended periods until they can be analyzed. In such cases, it is important to evaluate the long-term stability of stored samples to ensure data quality once they are analyzed.
How are Regulatory Authorities Responding to the Impacts of COVID-19 on Drug Development?
As regulatory agencies devote their full attention to reviewing tests, therapies, and vaccines for COVID-19, this could result in deprioritization of programs that are not related to COVID‑19. However, this response to the ongoing pandemic does not mean that regulatory authorities are ignoring the issues facing other therapeutic areas.
Global regulatory authorities including the FDA, EMA, and MHRA have promptly released several guidance documents for drug Sponsors since the start of the pandemic, all with one primary goal in mind – the safety of research subjects and patients. These documents have provided critical input on several issues related to study progression during the pandemic, including COVID-19-specific risk mitigation.
Regulatory agencies have demonstrated a great deal of flexibility and transparency thus far. In particular, the FDA guidance “Conduct of Clinical Trials of Medical Products during COVID-19 Public Health Emergency” has been maintained as a “living document” with multiple Q&A updates to address the evolving uncertainties associated with drug development in the current environment. Reviewing these guidance documents as they are released and updated is critical to ensuring that your development strategy is compliant with current regulatory thinking and expectations.
What Can Drug Developers Do if Their Studies Are Paused?
Even though clinical studies have been paused, there are still steps you can take to keep your program moving forward. When studies can be restarted, the goal should be for your study to start in a smooth and thoughtful way. If there is a large backlog of studies, clinical sites and CROs are going to favor studies that are ready to go on Day 1. For Sponsors, this mean ensuring that your protocol and study manuals are up to date, that potential issues have been addressed, and that all IRB approvals are in place. The key is to be proactive.
One thing companies can do to position their studies for success is to assess whether there are any useful data that can be evaluated now. These analyses could be used to terminate a study early (if sufficient data have already been collected) or could inform next steps in the overall development strategy. Evaluating data now might help Sponsors in their decision making on how best to progress their drug once studies are able to resume.
Now is also a great time to address any gaps in your development program. In this case, a gap analysis should consider both your overall strategy and potential issues related to COVID-19. One outcome of a productive gap analysis could be delaying less critical studies to focus on those studies most critical for approval.
In addition to the strategies above, taking the time now to re-group, get organized, and write critical study documents can give you a head start when clinics and CROs start accepting new studies. Updating new and ongoing protocols to address the unique safety considerations of the pandemic is particularly important while you are waiting to restart or initiate a new study. Finally, depending on where you are in your development program, consider using any “down time” to work on documents to support regulatory filings or other key regulatory interactions.
Drug development has not been spared from the negative impacts of the COVID‑19 pandemic. With the flurry of investigations surrounding therapeutics and vaccines intended to treat and/or prevent the spread of the novel coronavirus, drug development programs related to other indications have taken a temporary backseat. During this difficult time, it is important to consider what you can do now to strengthen your drug program for the future.
Nuventra’s team of experts are here to support your needs through:
- Strategic gap analysis
- Protocol review for COVID-readiness
- Interim analysis of paused and planned studies and other activities related to strengthening your development program
Lastly, Nuventra is committed to doing our part in fighting this global pandemic by helping Sponsors bring their COVID-19 vaccines and therapies to the general population as soon as possible. Our team has years of experience in developing therapies for viral infections, and we have former FDA staffers who are ready to help.
Please contact us with any questions you may have related to developing your vaccine or anti-viral therapy.