It is not just recruiting and retaining patients that make rare-disease studies particularly challenging, it is also identifying and setting up the right sites, a survey of clinical development decision-makers has found.

More than two-thirds (69%) of respondents in the survey commissioned  by Premier Research, the clinical-development services company based in Philadelphia, US, regarded finding and implementing qualified sites as among the most difficult features of getting rare-disease and orphan-drug trials off the ground.

 “Much of the success in patient recruitment is based on finding the appropriate site for the small patient populations we have to work with,” said Angi Robinson, Premier Research’s executive director, clinical trials management.

If patients need to be imported from outside Western markets, the complications multiply, Robinson noted.

For example, Premier recently flew patients in from the Middle East to a rare-disease trial in the UK, necessitating “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”, the company noted.

Regulatory barriers

In the survey involving 50 biotechnology and pharmaceutical companies in North America and Europe, regulatory requirements also emerged as a significant barrier to trial set-up.

More than two in five (43%) respondents said securing regulatory approval for the design of a rare-disease study was “difficult” or “extremely challenging”.

Engaging earlier rather than later with regulatory agencies seemed to help here.

Just over two-thirds of respondents (67%) either “strongly” agreed or agreed that regulators were more flexible when giving advice and/or direction during a post-Phase II meeting than when reviewing data for a new drug application. 

Despite these problems, 88% of survey respondents felt the number of patients they had to enrol for a rare-disease/orphan-drug trial was reasonable, Premier reported.

Advocacy boost

As the company noted, advocacy groups and medical networks play a significantly role in the clinical development of rare-disease/orphan-drug compounds.

The survey results showed that advocacy groups were used by 60% of respondents to help them with site or patient recruitment for rare-disease/orphan-drug trials.

Just over two-fifths of these respondents (42%) said using advocacy groups to meet patient recruitment goals was “successful” or "vital to the programme”.

About four in 10 (38%) felt advocacy groups were most helpful in increasing awareness of clinical studies.  

Roughly half of the respondents (46%) used medical networks to assist with site or patient-recruitment efforts in rare-disease/orphan drug trials. Of those who worked with medical networks, 32% described their experience as “successful” or “vital to the programme”.

Medical networks were far more productive in Europe than North America, with 63% of European respondents saying the networks were “vital to their programme” (18%) or “successful” (45%) in meeting patient recruitment goals.

Heavily outsourced

One measure of the complexity involved in rare-disease/orphan-drug trials is that 75% of these studies are outsourced to a contract research organization (CRO), Premier Research pointed out.

In the survey, 86% of respondents who outsourced their rare-disease/orphan-drug trials declared themselves “satisfied” with the CRO they had selected, while 50% said operational experience with small patient populations was one of the most valued CRO attributes in this field.

According to Premier Research, the company has managed around 100 projects apiece in rare-disease and paediatric research over the last five years alone.