Low patient accrual has historically been the primary cause of trial delays, suspensions, or terminations. This highlights the significant challenges in the recruitment of clinical trial subjects in a pre-pandemic world. It is therefore unsurprising that during the coronavirus disease 2019 (COVID-19) pandemic, an excess of 500 companies have announced that they have delayed initiation, suspended recruitment, or terminated clinical trials. When these trials resume, it is highly probable that potential trial subjects will have a heightened sense of anxiety regarding COVID-19 and therefore may have reservations about participating in clinical trials. This is especially likely in trials that require patients to be on-site, as hospitals and clinics are thought to be areas where COVID-19 is highly prevalent, thereby reducing patient confidence and making them less inclined to enrol.
In order to combat these enrollment challenges, sponsors must ensure that patient safety remains paramount and that all available safety measures are implemented. Investigators must adapt to the new set of standards required for in-person trials by having a parallel set of measures to the trial protocol, including routine COVID-19 testing and an enhanced level of deep cleaning. Sponsors must also ensure that adequate personal protective equipment (PPE) is available. Providing subjects with safe transport to and from the site should also be considered where available, as means of added incentive. All additional measures taken to prevent potential participants from contracting COVID-19 during their participation in a study must be relayed to the participants to increase their confidence in the safety of participating in trials.
In addition, direct-to-patient drug delivery with remote monitoring could increase the participation of subjects and alleviate concerns of potential COVID-19 infection by in-person visits. Regulatory authorities such as the FDA and MHRA have released new guidelines that promote the use of risk-mitigating strategies such as minimizing the number of participants at sites. Thus, a move towards decentralized clinical trials could mitigate the spread of COVID-19 while also being favourably regarded by the regulatory authorities.
Moving forward, trial coordinators must also take great care in selecting trial sites, giving priority to those who have previously utilized remote monitoring, as implementing new technology is typically a lengthy process.
Nevertheless, the move to decentralized trials raises a number of issues with the most pressing being subject safety unrelated to COVID-19. A lack of clinical supervision when administering investigational medical products (IMPs) with unknown safety profiles may compromise participant safety. For example, a lack of clinical supervision could lead to improper drug administration, potentially putting patient safety as risk while also potentially affecting the administered dosage. Trials that involve off-site self-administration will require participants to engage in a rigorous training program to ensure proficiency. This may be implemented through a combination of instruction manuals and online training. The method being utilized should be tailored to the trial population, such as a greater focus on the use of paper instead of digital manuals for older cohorts.
Additionally, proper adherence to trial protocols will need to be monitored effectively. For example, any deviation in administering investigational drugs from the study protocol by the participants will result in inaccurate conclusions being drawn regarding the drug’s safety and efficacy profiles. To overcome this, investigators must put in place a study compliance tracking system for dosing and sampling to send for lab testing where required. Furthermore, correct storage and adequate monitoring of the IMP is vital in preserving the integrity of the product. The study sponsors must outline the correct storage environment of the investigational drug.
In order to implement a direct-to-patient drug delivery program, the trial sponsors must ensure there is a reliable remote monitoring and data collection system in place. This system must ensure that subjects are adequately monitored, allowing for accurate reporting of adverse events and appropriate support when required. The system must also include a centralized data collection method to ensure that the data from each source can be sufficiently examined and compiled for complete evaluation. Trial coordinators should also look to increase the level of emotional support provided to patients to prevent feelings of frustration and isolation, which could ultimately lead to higher rates of patient drop out.
Although regulatory authorities have recently relaxed guidelines, it is imperative that investigators regularly communicate with regulatory authorities to ensure any new measures that they implement will comply with guidelines and that all measures are being taken to uphold the integrity of the trial.