The FDA recently released new guidance on drug development for the prevention and treatment of COVID-19, emphasizing the need for flexible trial designs, diverse patient populations and mechanisms to ensure data accuracy.
Digital components that empower decentralized recruitment, e-consent, symptoms/adverse events monitoring, wearable data capture, and telehealth visits could provide researchers with a path forward to ensure patient safety, while minimizing the strain on over-extended healthcare systems.
New, unique challenges face COVID-19 studies. Trial designs must consider hotspots where disease severity is highly variable, ranging from mild to mortal. Defining the start and end of the disease can prove difficult, as patients experience a myriad of symptoms rarely uniform in severity or duration.
Thus, the FDA has outlined several considerations for achieving diversity among the study population. Depending on trial design, it is recommended that researchers include a combination of in-patient and out-patient participants, health care workers and first responders, high-risk individuals with comorbidities, a geriatric population (via nursing homes or care facilities), and racial and ethnic minorities.
The Agency advises that, in certain instances, “…it may be appropriate to conduct decentralized or platform clinical trials.” The ability to employ remote-data collection, to shift geographies and rapidly enroll, use electronic consent/monitoring, is essential and these needs are addressed through the use of virtual clinical trial systems.
For treatment trials, the FDA advises “…sponsors to categorize the baseline severity of the enrolled population.” Symptoms such as fever, cough, sore throat, malaise, headache, muscle pain, gastrointestinal symptoms, shortness of breath, or dyspnea should be tracked without significant gaps in data. Many symptoms can be troublesome to record, as terminology needs to be defined, and the severity and duration of symptoms can impact data accuracy.
The development and use of novel specific patient reported outcomes (PROs) and electronic PROs (ePROs) is vital in characterizing the baseline severity of the disease, the short term symptomatic phase and the long term follow up period where further manifestations of this disease may emerge.Sending patients an app to enroll, consent, monitor symptoms and conduct telehealth visits on their smartphones enables reminders and email alerts for diary completion. This helps minimize missing data and can be rapidly deployed to the needed populations while maintaining and maximizing safety considerations.
Patients and healthcare providers are facing unprecedented challenges: inaccurate patient reporting of symptoms, symptom measurement tools that are not well developed or sufficiently specific and social distancing between patients and providers. In addition, constant news about COVID-19 research influences both beliefs and behaviors and may increase placebo response rates. As a result, virtual patient training on accuracy in reporting will be key to the success of COVID-19 studies. Both parties need training on their responsibilities in the study. This includes expectations, importance of PRO/ePRO diary compliance, medication adherence and the role of placebo within the research. The more diverse the population, the more critical it becomes to deploy standardized training so that patients and providers align on objectives.
Training in COVID-19 studies may help to avoid false-positive outcomes and accurately enroll the target population at baseline. For example, if patients inflate baseline symptoms, then enter a study as moderately symptomatic and rapidly “improve” once enrolled, it cannot be known whether the study drug was efficacious. Virtual training on the importance of accurate reporting can facilitate precise baselines and enable true clinical signals to emerge.
Finally, patients must understand their symptoms to report them; training on the symptoms is essential. Developing drugs to prevent and treat COVID-19 has brought a unique set of clinical challenges and emerging variables. Virtual solutions are poised to rapidly provide flexibility, access, and information – enabling trial designs to adapt as interim analyses are conducted. Most importantly, they increase the likelihood of accurately eliciting both efficacy and safety signals.