Greater Trial Flexibility Critical to Further Implementation of Innovative Approaches
To take full advantage of innovations highlighted during the pandemic and apply them to future trials, certain barriers, including protocol complexity, limited resources and cumbersome review processes, need to be overcome.
First, using simpler, broader protocols can encourage the adoption of innovative approaches without requiring formal protocol amendments, according to a new report from the Good Clinical Trials Collaborative (GCTC).
Gathering feedback from more than 500 researchers involved in trials, the collaborative saw strong consensus that protocols should allow for pragmatic adaptations without requiring new approvals, which can cause delays and serious repercussions for trials.
“For example, a flexible protocol may describe the need for a consultation but not dictate how it will be conducted, allowing the option for in-person, phone or video-call consultations, depending on the circumstances,” the report said.
More than half of researchers said they had to make changes for their trials to continue, a good deal of which could only be enacted through formal protocol amendments. Others cited issues caused by delayed approvals, including the loss of primary data and patients having to end treatment, and others suggested they avoided certain implementations because they believed approval would take too long.
Second, it’s important to make sure that the proper infrastructure and resources are in place to support innovative approaches. Certain flexible and decentralized approaches, such as direct-to-patient services and remote data collection, can fail when the proper amount of resources aren’t allocated.
For example, GCTC found that some trials were unable to shift to using electronic case report forms (eCRFs) during the pandemic because they relied on paper CRFs, which posed logistical and data protection challenges during remote working and caused frustration. Having to adapt to remote and hybrid operating approaches during the pandemic illuminated the reliance of many trials on paper forms, the report said.
On implementing innovative measures, concern mostly centered on inappropriate resources rather than the measure itself. Researchers noted that certain staff couldn’t do electronic/telephone followups from home because they lacked the right equipment or didn’t have a fast-enough internet connection. This concern about lack of resources spanned several areas, including consenting, data collection, direct-to-patient delivery and the use of local services, according to the report.
Lastly, a more coordinated approach to ethics and regulatory reviews is critical to fully opening the door for the adoption of innovative strategies. This would, for instance, help streamline the approval of amendments and simplified protocols and cut down on unnecessary work for trial staff. Researchers suggested that a more coordinated way of reviewing amendments might help ward off trial delays and make reviews more efficient. Additionally, trials with multicenter studies said that they would like to see ethics reviews be valid for all participating centers, whether they are global, regional, national or local studies.
“A more streamlined process could contribute to less unnecessary work for trialists and reduce the number of amendments each center must process,” the report suggested.
The collaborative cautioned that any moves to increase flexibility should be backed with “a proportional and evidence-based approach” to ensure that the changes benefit the participants.
GCTC found that 95 percent of the researchers it communicated with reported being affected by the pandemic, but with adaptations, 56 percent were able to carry on. Just over one-third (37 percent) said their trials were paused or suspended, while only a small fraction (2 percent) said they had to pull the plug due to the pandemic.
Remote and electronic consenting approaches, for instance, were viewed positively by researchers, many of whom said they would likely use them again. These approaches included getting consent over the phone, using tablets to record consent and other measures of obtaining consent without a physical signature on a document. Inefficiencies in traditional consent methods were noted, including their being overcautious or repetitive, and the suggestion was raised that it may be possible to cut down the amount of times patients are asked to consent.
Remote data collection was also employed during the pandemic, with many trials using virtual assessments, samples sent by mail and eCRFs. But in this area, concerns were raised; researchers reported not all outlets were suited for the approach, meaning there was a reduction in the total amount of data collected. For example, the remote collection of physiological data, such as imaging and blood biochemistry, was particularly challenging, and trials that directly relied on these measures had to stop, according to GCTC.
Importantly, the quality of data gathered by remote data collection, particularly where patients measured their outcomes themselves, was flagged as an area of worry. Some home tests were less accurate than the ones used by trial staff, for example, and other home tests were simply not good enough to yield useful results. The researchers suggested that using reliable home tests and specialist equipment (including home blood pressure or lung function testing equipment) might help increase the quality of remotely collected data.
Direct-to-patient deliveries were viewed in a generally favorable light, but again, there were concerns and bad experiences. Some encountered logistical barriers, including mail service delays, while others ran into country-level regulations that limited what they could ship by mail. Some trials encountered additional complications when they were shipping medical products internationally, and others had concerns about maintaining data protection, privacy and blinding. Overall, the consensus was that direct-to-patient services made trials harder to carry out, though some still felt they were worthwhile in the end because of the benefits to participants.
Remote visits and the use of local services were viewed favorably, with decentralized approaches improving the patient experience and online/local assessments and intervention delivery deemed convenient and easier for the patient. Some researchers did note that they ran into a lack of resources that led to more work for some staff, and others expressed concerns that decentralization made trial management a greater challenge.
In August, GCTC called for public feedback on the first draft of its guidance for good RCTs, putting forward recommendations for data management approaches, trial size, statistical analysis, safety reporting, collaboration with other organizations, use of existing resources and effective trial monitoring (CenterWatch Weekly, Aug. 9).
For the full report, contact GCTC at www.goodtrials.org.