Clinical Researcher—May 2020 (Volume 34, Issue 5)

GOOD MANAGEMENT PRACTICE

Ryan Bailey, MA

As the world grapples with the coronavirus (COVID-19) pandemic, many in the clinical research community are eager to support trials that will help us better understand the virus and how to treat and prevent it. However, conducting urgent infectious disease research poses unique challenges for researchers, not least of which is the pressure to respond as quickly as possible to identify successful treatments for those who are or could be affected by the illness.

Although COVID-19 is unprecedented in its worldwide impact, we can look to previous pandemic research to guide us in these efforts. Following the 2009 H1N1 outbreak, Rho helped coordinate a trial to assess the safety and immunogenicity of an H1N1 vaccine in adults and children with severe asthma. Our experiences with that trial and other infectious disease studies in recent years have taught us a few lessons about running trials during a pandemic.

Rely on Existing Relationships

Pandemic research is driven by an incredible sense of urgency as infections spread and people tragically lose their lives. We are compelled to mount a rapid response, but we must do so without jeopardizing patient safety or the scientific rigor of our research.

One of the strategies we rely on is to take advantage of existing partnerships and data sources to expedite study start-up and patient recruitment. For instance, pandemic research may not be the best time to attempt to work with a number of new sites. Instead, this is a good time to utilize any existing relationships with sites that have a proven record of success to ensure more streamlined operations.

While it is not always feasible to rely on sites you have worked with previously, you cannot underestimate the efficiency gained from working with tried and true partners.

Address and Overcome Barriers to Patient Recruitment

Another tactic we recommend is to use patient databases and registries for subject recruitment. One of the biggest hurdles to conducting a timely trial is identifying and enrolling your target population. Look for opportunities to tap into patient registries where you can pre-screen subjects for eligibility criteria. Likewise, this can be a good time to leverage relationships with patient advocacy groups, which often have access to patient networks in your target demographic and may be willing to help promote your study.

Patient registries can also be helpful if they allow you to recruit subjects with prior experience participating in clinical trials. Enrolling research veterans can lead to better participation and adherence, especially if you need to rely more heavily on virtual clinic visits during a time of social distancing.

The participant with prior experience in a trial will likely be better prepared to handle the challenges of participating remotely. However, while such groups can be advantageous for quick enrollment, take care to ensure you avoid introducing bias by recruiting a sample of convenience.

Additionally, patient registries or electronic health records can be an important source for collecting pre-existing data. Having information about a patient’s diagnoses, comorbidities, and medications already on hand can save valuable time, as it provides important baseline data that you would otherwise need to collect through lengthy questionnaires. Similar to the process of enacting patient recruitment strategies, you also want to balance convenience with scientific rigor to ensure such data are timely and reliable.

Prioritize Participant Care and Education

In the rush to launch a trial, be careful to not overlook the mental and physical needs and limitations of participants. Trials can be demanding, especially if participants are asked to undergo a variety of procedures and follow ups for data collection in a short window of time. To ensure the utmost comfort and peace of mind among your patients, seriously consider the collective visit and data collection burdens being placed on these individuals to ensure they are reasonable and manageable.

The uncertain and evolving nature of a pandemic will certainly evoke some level of fear and anxiety among potential trial participants, and they may display some reluctance to participate due to fears about the disease or treatment. Site teams have an ethical responsibility to carefully explain all potential risks to the participant during the consent process, but you may also need to help dispel fears that are based on misinformation or misunderstandings.

Maximize Your Monitoring Strategy

Another way to gain efficiency is to think critically and creatively about your approach to clinical monitoring. With travel restrictions in place, how can you shift to more remote monitoring? Is 100% source data verification needed, or can you get by with a risk-based model that reduces the monitoring burden? Can you combine the purpose and type of visits into fewer interactions? This could look like combining site qualification and initiation visits, especially for sites with a history of success, to help buy more time in moving the trial forward.

You will also want to consider how the unique characteristics of infectious disease trials impact your plan for data monitoring. Many trials monitor data collection on a routine basis, but the rapid pace of pandemic research requires close and more consistent data monitoring and management. Such studies should implement a process for monitoring patient safety data and any other critical variables on a frequent or even daily basis, making sure to still observe blinding rules.

Data visualization tools are valuable at this stage in terms of providing data insights as well as the rapid identification of outliers and trends that may require closer scrutiny. Whatever the case, any planned changes to traditional clinical and data monitoring should be addressed early on between sponsors, contract research organizations, and participating sites to ensure important steps are not sacrificed in the name of expediency.

Opt for Simplicity

A common temptation during trial design, especially in epidemiological studies, is to collect as much data as possible from participants—the rationale being that a more robust dataset will yield more new knowledge about the disease.

However, additional data collection drags out all phases of a study, from planning and start-up to execution, data management, and analysis. The best way to fight these costly delays is to push for simplicity in trial planning; this may include making sure the protocol does not get bloated with unnecessary visits, procedures and data collection. Instead, focus on only the most important outcomes and be disciplined in keeping the study simple and straightforward.

Likewise, it is important to keep in mind that even when a therapy fails to produce the hypothesized outcome, such results are still important for public health. With novel viruses and outbreaks, any scientifically sound information is valuable. While negative results are disheartening to researchers and patients alike, they are important for ruling out ineffective treatments and guiding future research.

Conclusion

Pandemics are urgent and unpredictable, and they rarely offer the ideal setting for conducting controlled clinical trials. Despite these challenges, clinical research plays a critical role in the treatment and prevention of infectious disease outbreak

The unique nature of clinical research during pandemics requires researchers to move as swiftly as possible without sacrificing the safety and well-being of subjects and overall data integrity. To achieve this balance, we recommend leaning on existing networks of sites, patient registries, and databases to expedite start-up and enrollment; planning ahead for the needs of your patients; thinking creatively about your monitoring plan and data monitoring strategy; and prioritizing simplicity in trial design.