Research organizations closely analyze sponsors and studies for a good match
Key strategy: Send sponsors questions
Both new and mature clinical research organizations can reduce clinical trial problems and failures through initiating or improving protocol feasibility analysis processes.
"We don't want an investigator to sign a contract with a pharmaceutical company and not fulfill that contract because we don't have the resources or patient population," says Marietta Barton-Baxter, CCRC, administrative director of the Clinical Research Development and Operations Center (CRDOC) at the University of Kentucky in Lexington, KY.
So the key is to thoroughly analyze each protocol to make certain its patient population, enrollment goals, timeline, and other aspects will fit with a particular research organization, she says.
For new central clinical trials offices, protocol feasibility analyses are a way to create a more efficient and effective CR process from the start, says Rachel Sheppard, MBA, CCRA, CCRC, project director of the Office of Clinical Research Services and Support at the University of Louisville in Louisville, KY.
Although the University of Louisville central clinical trials office was established in July, 2008, the office's core group has been working together for about nine years as a departmental research institution, Sheppard says.
The office now has 120 trials entered in its database, and 17 protocols have been rejected, mostly based on inclusion/exclusion criteria, but also some rejected based on timeline, she says.
The protocol feasibility process is voluntarily offered to investigators and departments and not everyone participates, she says.
Sheppard estimates the study's success rate in enrollment is close to three times greater for protocols that have been through the feasibility process than for those that were not submitted to the process.
"Over time we saw that many of the projects we accepted were not appropriate," Sheppard says. "We had many instances where we felt we could have done a better job of investigating the research before we accepted it."
The old paradigm was that sites should accept any research protocols sponsors offered.
"That, of course, is not the case," Sheppard says. "So we wanted to evaluate protocols in a more efficient, standard way."
The key is to develop a protocol feasibility analysis process.
This can be a formal process in which various people are assigned roles and have tasks to complete, or it can be an informal process in which experienced CR employees make recommendations based on their past experience.
For instance, the CR office at the University of Kentucky has a less formal process that relies on the expertise of its staff to weed out inappropriate protocols, Barton-Baxter says.
Here are suggestions for establishing or improving a protocol feasibility analysis process:
1. Find out more about the protocol and sponsor.
Both the University of Kentucky and the University of Louisville CR offices send sponsors questionnaires as part of their protocol feasibility process.
If a CR organization has had no past experience with a particular sponsor, then it'd be wise to research the sponsor's reputation and past performance, Sheppard and Barton-Baxter suggest.
"I'm a member of a number of different site manager list servs," Barton-Baxter says. "I know which pharmaceutical companies are not on the up and up."
Also, the University of Kentucky contracts with many sponsors repeatedly, so the CR office knows how each handles studies and issues that arise during a trial, she adds.
"Every time I have this discussion with people who are new to this field, everyone wants a fail-safe way to see if it's feasible for them to do this study," Barton-Baxter says.
But there are no guarantees, she adds.
Sites can do their best to make certain a sponsor is reliable and fair, and then only experience will show if their judgment is correct.
2. Ask for opinions from various experts in your organization.
"When we're just starting to look at a study, we get all of our troops together to look at where we are," Barton-Baxter says. "We have a working meeting at the beginning of every study."
Usually, this means the principal investigator (PI) will meet with the regulatory manager, clinical manager, and marketing and recruitment manager, if the clinical trial will be utilizing all of these resources, she notes.
At the University of Louisville, various CR disciplines also are involved in the protocol feasibility process, including the investigator, regulatory manager, and clinical team, Sheppard says.
Various individuals give a recommendation for whether the organization should do this particular study, she adds.
Then, one person reviews the recommendations and makes a final decision.
"We leave it up to each individual department to decide how they want to approve feasibility," she says. "For some it's the department chair that makes the decision; for others it's the principal investigator."
3. Use a feasibility form to document criteria and decision.
"We have a feasibility form that we complete internally for evaluation of the protocol," Sheppard says. "The form is important to us because it provides information on the protocol in an organized way, based on functional areas."
For instance, there's a section on impact, which is very important to PIs, she notes.
"Investigators look at the impact of the protocol on patient care, reputation, academic activity," Sheppard says.
The PI will answer the questions in this section and then make a recommendation about whether the study should be done based solely on the study's expected impact, she adds.
The form asks PIs to make a small explanation for their recommendation.
"If there is no other treatment for the patient or patient population then they are encouraged to give more information on the form," Sheppard says. "They might say, 'This protocol is very important to this population, so unless there are considerable financial issues, I'd like to proceed.'"
The form also has a section on enrollment. PIs and the clinical team will examine the protocol's inclusion/exclusion criteria to see if they're appropriate for the site's patient population, Sheppard says.
Another section involves procedures.
"We look at whether the protocol's procedures are in line with our standard practice," Sheppard says. "We address whether they are ethical for the patient population and whether they'll be difficult to schedule."
Clinical trial coordinators, PIs, and the clinical team collaborate on making a recommendation regarding the procedures section.
A financial section is reviewed by the CR financial manager, who answers questions about whether the site has worked with this sponsor or clinical research organization (CRO) in the past and if there was a successful financial relationship, Sheppard says.
"Is the company solvent? Have all the expenses of the trial been identified in a draft budget?" she adds.
The general protocol section discusses whether the protocol agrees with ethical judgments for patient treatment, she notes.
"Is this study similar to other projects we've performed in the past? Are there any issues related to placebos or standard of care, special equipment, subject compliance?" Sheppard says. "We take an overall look at the protocol and ask whether we anticipate any problems in IRB approval."
The clinical team and regulatory manager review this section.
Another section relates to sponsor expectation, and this one will include information from the sponsor questionnaire about the study's timeline, number of subjects expected to be enrolled, and the duration of the project, Sheppard says.
After each section of the six-page form, an assigned person makes a recommendation, putting his or her initials beside either recommended or "not recommended."
Occasionally, reviewers will disagree and they might write a note documenting the disagreement, such as the following: "I don't think this is a problem, but the rest do," Sheppard says.
Also, the person who makes the final decision should document reasons for turning down a particular study, and these typically are sent to sponsors.
"We encourage that person if they reject the study to identify the reason for rejection so we can send it back to the sponsor," Sheppard says. "If they decide to have a protocol amendment then it could impact our decision whether to participate in the study."
At times, the organization has heard from sponsors who have asked the research team to take a second look at a study after they made changes based on the feedback, she says.
There was at least one case where the institution did reconsider and accept a protocol that had been changed, she adds.
The protocol feasibility program has been successful thus far.
"Study coordinators are very happy with this feasibility process because they feel like they finally have a say in how trials are accepted," Sheppard notes. "The PIs also feel they get a say in the evaluation because of the impact section."
The process is being tweaked as it evolves.
"Since this is a new process, we're still defining how to make it a better and faster process because it does add time at the beginning of a study," Sheppard says. "But we feel like we're doing a better job of selecting trials now and in the long run there are fewer people spending time on a trial that won't be successful."
Both new and mature clinical research organizations can reduce clinical trial problems and failures through initiating or improving protocol feasibility analysis processes.You have reached your article limit for the month. Subscribe now to access this article plus other member-only content.
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