Premier Research's New Rare Disease and Orphan Drug Survey Accentuates Difficulty of Recruiting Patients, Motivating Patients to Take Part in Study

A new survey of clinical trial decision makers commissioned by Premier Research and involving 50 biotech and pharmaceutical firms in North America and Europe reveals that more than two-thirds (69%) of respondents said that among the most difficult factors in recruiting patients into a rare disease clinical trial was not only finding and motivating patients to join and remain in trials, but identifying and setting up investigative sites for studies.

"Much of the success in patient recruitment is based on finding the appropriate site for the small patient populations we have to work with," Premier Research Executive Director, Clinical Trials Management, Angi Robinson said. "It's worth noting that these studies become even more difficult to manage when they are conducted outside of Western markets."

An example of this was brought to life recently when Premier flew patients from the Middle East to a trial in the UK, which required oversight of countless details from arranging for transportation of patients and parents, to visa requirements, language issues, and ongoing follow up with patients upon their return home.

Nine of 10 (88%) said the number of patients they are required to enroll in a rare disease and orphan drug study is reasonable — a surprising finding given the inherently smaller universe of patients available to enter such a study and the respondents' perception of the difficulty in finding qualified sites and recruiting patients.

Regulatory Factors

More than two in five (43%) respondents said that securing regulatory approval for the design of their clinical study was "difficult" or "extremely challenging."

Interestingly, just over two-thirds of respondents (67%) either "strongly agree" or "agree" that regulatory organizations are more flexible when giving advice and/or direction during a post-Phase II meeting than they are later on in the review of data during the "NDA," or new drug application process.

"There is a belief that regulators are fairly realistic in discussing clinical trial design when it comes to developing new treatments for rare diseases," Premier Research VP, Regulatory Affairs and Pediatric Consulting, Charli Sanders, M.D., said. "Experience in working with regulators can help to facilitate the process."

Adaptive Design

Adaptive trial designs are used in rare disease/orphan drug studies at a rate that roughly mirrors more traditional study penetration. "This was somewhat unexpected as we thought adaptive design would be more prevalent with a smaller patient pool," Robinson said.

The use of adaptive trial designs is relatively low, but in comparison to the overall penetration of these designs, there seems to be some interest in using them for rare disease/orphan drug studies. Only two-fifths of respondents indicated that none of their rare disease/orphan drug trials utilize adaptive trial designs.

Advocacy Groups and Medical Networks

Advocacy groups and medical networks play a substantial role in the clinical development of rare disease/orphan drug compounds, and, in fact, advocacy groups were used by more than half (60%) of the respondents to assist with their site or patient recruitment.

Just over two-fifths (42%) indicated that the use of advocacy groups to meet patient recruitment goals was "successful" or "vital to the program."

"Advocacy groups and medical networks have great potential to aid in patient recruitment and sponsors recognize the importance of working with CROs that have those relationships," Robinson said.

• Nearly four in 10 (38%) said advocacy groups were most helpful in increasing the awareness of the clinical studies. Respondents were quite divided about what the challenges were in working with patient advocacy groups:

• 24% said the patient advocacy groups needed more convincing as to how it would benefit them and/ or their patients before they would assist;

• 17% said communications and logistics needed to be improved;

• 10% said there were contracting or legal issues; and

Roughly half of the respondents (46%) used medical networks to assist with site or patient recruitment efforts. Of those who had worked with medical networks, one-third (32%) said their experience had been "successful" or "vital to the program" in terms of meeting patient recruitment goals and timeliness.

Medical networks were much more successful in Europe vs. North America. In fact, 63% of European respondents indicated medical networks were "vital to their program" (18%) or "successful" (45%) in meeting patient recruitment goals.

Of the dozen respondents who had experience with both patient advocacy groups and medical networks, nine (75%) indicated that patient advocacy groups were more helpful in meeting their patient recruitment goals.

Complexity of Rare Disease Trials Leads to Use of CROs

The complexity of rare disease trials underscores why 75% of rare disease/orphan drug studies are outsourced to a contract research organization (CRO).

The vast majority of respondents who outsourced their rare disease/orphan drug trials were "satisfied" (86%) with the CRO they selected.

Half (50%) of survey respondents indicated that operational experience with small patient populations was among the most valued CRO attribute.

Expanded Access and Compassionate Use Programs

Expanded access/compassionate use programs are common among rare disease/orphan drug trials. More than one-half (59%) of respondents indicated that half the time or more their company runs an expanded access or compassionate use program alongside their rare disease/orphan drug trial.

Rewarding Work

Compared to traditional clinical trial populations, the vast majority (73%) of respondents indicated that working on rare disease/orphan drug trials was either "somewhat more rewarding" or "incredibly rewarding."

"You can hardly overstate how gratifying it is to be a part of a team that develops a treatment for a rare medical condition, especially when it involves children, as many of these rare diseases do," Robinson said. "Our fondest wish is to play a role in the effort that finds a cure for these illnesses."

About the Survey
For this survey, 50 clinical development decision-makers in the US and Europe were interviewed by an independent third party research firm during February 2013.