For Faster Trials, Improve Feasibility

Clinical trials are expensive and slow, but we are on the precipice of change. My aim is to bring people together to accelerate trials. One area that could accelerate trial execution (and reduce burden) is improving trial feasibility – the process by which a sponsor or CRO identifies trial sites; indeed, this area is ripe for better collaboration. Put simply, trial feasibility involves inquiries about the principal investigator, site facilities, projected patient enrollment, and additional administrative matters.

The current process is broken – and those fractures have downstream effects that negatively impact every stakeholder. A recent survey found that 49 percent of sites think the burden of feasibility questionnaires has worsened over the past few years, and 30 percent consider the current feasibility processes to be very or extremely burdensome. Burden leads to burnout, which leads to an increase in personnel, which necessitates higher overheads. It’s high time we fixed these burdens – especially given the relative ease with which to implement solutions. In fact, some remedies are a matter of common sense. Here, I share eight uncomplicated dos and don’ts to improve feasibility for faster trials.

1. DO automate feasibility forms
 

Completing feasibility forms should be more automated and less manually repetitive. At a busy site, hours are spent each week on admin and entering information considered to be basic capabilities of any research clinic, such as whether they have a refrigerator for drug storage and a centrifuge for processing blood samples. Why don’t companies retain this basic information for preferred principal investigators? Imagine filling out nearly identical New Patient Intake forms multiple times a day. Unless working with a new principal investigator, all previous form responses should be pre-populated for the site, with the option to update any form with new information. 

2. DON’T limit sessions for online feasibility forms
 

To ensure accuracy, online feasibility forms need to be editable over longer periods of time, including multiple online sessions. Why? Sites need this time to analyze the patient population and consult with the lead physician and auxiliary services, such as pharmacy and infusion nurses. The more departments involved, the more edits there are likely to be and the longer the process will take – up to a few days, even at sites that move quickly. Managing full clinical schedules leaves less time to devote to research. 

3. DO preview the feasibility form with sites
 

Sponsors and CROs should set up roundtables with site personnel to review the feasibility form prior to use to identify questions or concerns – and rectify them upfront. In certain chronic conditions, for example, excluding other conditions drastically decreases the number of possible patients who qualify for the trial because of common comorbidities. In other cases, a poorly devised visit schedule can lead to unnecessary dropouts. Research staff with experience in the study’s therapeutic area can be instrumental in identifying and thwarting issues before it’s too late.

4. DON’T expect a two-page protocol summary to be enough
 

Sites cannot be expected to know how many patients they can enroll based on a two-page protocol summary! This does not give the site all the inclusion/exclusion criteria needed nor does it offer insight into what the true lab and IP requirements are, how the trial compares with standard of care, and whether or not the trial will be accepted by the community. 

There is no informed feasibility without a full and final protocol. Summaries set sites up to give bad information about patient enrollment, which will later appear as false. It may also lead to sites having to defend not meeting enrollment goals, which (ironically) leads to numerous emails and meetings that distract from the job of enrolling patients. Leadership at the sponsor must then report back to stakeholders about a trial’s underperformance; Gantt charts and milestones are created around expected enrollment rates, and every projection from the site, the CRO, and the sponsor is proven wrong. 

5. DO conduct feasibility form reviews as a matter of business
 

The sponsor or CRO should conduct a post-enrollment review to see if the original feasibility form reflected the reality of the trial. Did the sponsor/CRO get the most critical information into the feasibility questionnaire, reflecting the key points for patient enrollment? Were there large discrepancies in feasibility answers versus actual enrollment, or were most sites on target? If there is a consistent trend of discrepancies, it is a telling reflection of subpar trial-specific questions.

6. DON’T get ahead of yourself with site initiation visits (SIVs)
 

Do not hold SIVs if there is a reasonable chance that the protocol will be amended over the first few months. First, this is excess work for everyone and will slow enrollment on most trial types. Second, site teams will need to be retrained, which is rife with the possibility of protocol deviations. Third, the clinical trial management system (CTMS) must be entirely updated with changes that affect the visit schedule and possibly the budget. Not all CTMS systems have change dates for amendments, which can be an extremely labor-intensive process. Fourth, the sponsor/CRO likewise faces the possibility of increased protocol deviations and the invisible and actual costs of budget amendments.

7. DO keep the patient and physician relationship in mind
 

If the protocol amendment changed inclusion/exclusion (I/E) criteria, or anything that might change physicians’ or patients’ interest in the trial, this will decrease patient enrollment and sour the physicians’ relationship with the sponsor and/or site. For certain trial types, providers are excited to talk to their patients about a trial, and begin doing so months in advance. Hurting the provider–patient relationship is a sure way to destabilize the trial’s success. (It probably goes without saying that I/E changes also nullify the original feasibility form responses.)

Sponsors and CROs must recognize that meeting the first patient/first visit milestone is less important than the milestone of completing enrollment. It is better to start a trial a few months behind schedule and meet the enrollment date and goal (with fewer protocol deviations) than it is to meet the first patient/first visit goal and suffer inefficiencies through the entire trial lifespan.

8. DO enlist a site ambassador
 

Every large site has people who can explain what is good, bad, or neutral about any feasibility process. The people who complete dozens of these per week have opinions about every CRO’s and sponsor’s process. Engage the most vocal of these people, and you’ll be set for incredible success.

Think long term for success
 

To summarize, companies that focus on short-term milestones will always face delays. Rushing or short-cutting the feasibility process will cause problems downstream that end up being even more costly than a delayed startup. So, “measure twice, cut once” by submitting the full, final protocol to sites for their experienced re-assessment prior to starting any trial startup activities. 

Take a collaborative approach to feasibility. The full process should be i) initial feasibility form, ii) study award, iii) final feasibility form, iv) decision by both parties to proceed, v) study startup launch. Follow these steps to increase the accuracy of enrollment projections and actual enrollment – and ultimately accelerate trial timelines.