Survey Notes Continued Confusion About PREA and PIP; Many Sponsors Unaware of FDA’s Priority Review Process
PHILADELPHIA, July 20, 2015 — A new survey of clinical trial decision makers commissioned by Premier Research reports that identifying an adequate number of children suitable to be patients is far and away the single greatest challenge in conducting a pediatric clinical trial.
The Premier Research survey also revealed a surprising lack of awareness among clinical trial sponsors that, as part of the Safety and Innovation Act (FDASIA), FDA will award priority review vouchers to sponsors of rare pediatric disease product applications that meet specific criteria.
“FDA’s Rare Pediatric Disease Priority Review Vouchers Draft Guidance for Industry can benefit sponsors tremendously,” Premier Research’s Director, Regulatory Affairs, Nachiket Dave said. He noted that products which undergo priority review generally are given an approval decision — positive or negative — within six months of the filing date, rather than the usual 10.
“Yet 96 percent of survey respondents indicated they have not even read the FDA guidance,” Dave said. “So it should come as no surprise they have little to no understanding of the priority review process.”
For this survey, 50 clinical development decision makers (mainly U.S./Europe) were interviewed by an independent third-party research firm in May 2015.
Six in 10 Claim Too Few Patients to Meet PREA
The difficulty in recruitment reported by Premier Research in its 2012 benchmark survey on pediatric clinical trial challenges continues today, three years later, to be a major issue for the majority of respondents. In fact, six of 10 respondents agreed that if every company complied with PREA*, there would not be enough patients to fill the studies.
PREA (Pediatric Research Equity Act) requires biotech and pharmaceutical companies to study their products in children. When pediatric studies are required, they must be conducted with the same drug and for the same use for which they were approved in adults.
“Recruitment for pediatric populations will always be challenging because it comes down to dealing with parents,” Premier Research Executive Director, Pediatrics and Rare Diseases, Angi Robinson said. “You’re talking about volunteering your child for research. You think twice. We make every effort to reduce the burden on the family. Predictive modeling is one way we do it. Identifying mitigating strategies is key, because the basics won’t change.”
Robinson noted that while pediatric research may never be easy, having the medical infrastructure and knowledge — its own pediatricians, investigative sites, and relationships with pediatric patient networks and advocacy groups — gives Premier Research an edge. “The growth of patient networks is the biggest change for the better we’ve seen in the past three years,” she said.
She added that the Premier Research Pediatric Certification Program is another way the CRO immerses its team in a pediatric environment. “We created a proprietary five-module educational program that’s required training for our operational staff,” Robinson emphasized.
“It covers guidance, consent and assent, medical considerations — it runs the gamut,” she continued. “We adopted it in 2014 and continue to evolve the training curriculum to stay ahead of the curve.”
Meeting the Challenges of PREA Compliance
Sponsors continued to find complying with PREA to be highly challenging. One third did not know there was room for sponsors to amend and revise their PREA obligation, nor were they even sure of how to initiate the compliance discussion.
“There continues to be a lack of transparent understanding and comfort level with PREA, irrespective of sponsor size,” Dave observed. “The smaller biotech startups tend to need more help because they have less expertise than the big pharma companies. But competing priorities and competition for resources means that sponsors at all levels haven’t created the internal level of expertise needed to deal with PREA. That’s why they reach out to CROs.”
Dave noted that “there is always a learning curve with any new regulations,” he added, “and at the same time we’ve seen a steady influx of micro firms into the pediatric clinical space. The micros have not had the time to accumulate the institutional knowledge of big drug companies.” He added that the PREA pediatric review process is quite specialized.
“Not surprisingly, we have seen where sponsors have started a pediatric program that was poorly designed or the protocol was not suitable to recruit patients or the site they were using was not performing well. Traditionally, because so many companies design protocols just for adult populations,” he explained, “they tend to design their pediatric protocols the same way. But pediatric populations are discrete. Premier Research is sensitive to the needs of these populations. We understand the pediatric patient, which you really have to if you’re going to design an effective protocol.”
EUROPEAN SURVEY RESULTS
Survey results from biopharmaceutical companies that operate in Europe were similar to the results from the U.S. respondents when it came to the issue of finding an adequate number of pediatric patients.
Only one in five respondents said they have a full understanding of PIP. One quarter have either no understanding of PIP or have never heard of it.
Dave noted that relative to the number of companies and size of companies doing research, the U.S. has the greater pool of clinical trials, but there aren’t significant hurdles in either region. “The U.S. really has caught up to Europe in opening the doors to pediatric research, such that there is even greater sharing of pediatric clinical trial data in the U.S. than in Europe due to FDA working more closely with its European counterpart, the EMA.”
He added that traditionally Europe has been somewhat more aggressive in getting pediatric compounds to market faster than has the U.S. “If you’re a biopharma firm,” Dave said, “your compound may make it to market faster in the EU simply because the EMA moves quickly. Once a new compound has been approved by the EMA, however, that can help win quicker approval in the U.S.”
Most Are Unfamiliar With Priority Review Process
Biotech and pharma companies in Europe tend to rely even more heavily on CRO outsourcing. More than seven in 10 (71%) sponsors in the EU said they call on outside expertise to ensure pediatric regulatory compliance. As in the U.S., that number is a major increase from three years ago.
“The rare pediatric disease priority review process requires special expertise,” Dave said. “In the U.S., not enough companies take advantage of what FDA offers.” He added that the priority review process provides sponsors with an opportunity for early dialogue and interaction with FDA.
“What an experienced CRO can do is to actually take the customer to FDA and sift through the layers of data,” he explained. “We want the agency looking at exactly the data our customer should be presenting. Inexperienced companies will deluge FDA with irrelevant data. Yet the whole point of the process is for FDA to expeditiously fast forward their review of a sponsor’s application. We move our customer along the FDA approval pathway as efficiently as possible.”
He added that underlying any successful priority review process is the network of relationships that a CRO has with key hospitals and researchers.
“At the end of the day this is a relationship business,” Dave stressed. “We have the kind of relationships that even transcend our expansive database of sites and trials. Our folks can pick up the phone and contact the heavy hitters in this space and gather data that other institutions and companies just can’t. You don’t build those kinds of relationships overnight either.”
Dave noted that Premier Research offers regulatory services that assist customers in complying with and managing pediatric commitments (e.g., PREA, PIP, PedEx, pediatric vouchers agreements). He added that Premier Research’s consultative services for the pediatric space — which, in many cases, are applicable to rare disorders — include, but are not limited to:
- PERT team protocol design, pediatric plan content production, and operations consultations.
- “Walk the protocol” simulations.
- FDA special meetings and engagements for agreements.
- Population pharmacokinetic (PK) plans and interactions for agreements.
- PRPs/PIP authorship and amendments and modifications/appeals.
- Re-engagement and re-medialization of PREA/PIP agreements.
- Regulatory data research and pop PK model design and simulations.
- Data extrapolation (both animal and human) for use in pediatric plans and/or endpoint determinations, as well as dose finding/selection for pediatric patient studies.
About Premier Research
Premier Research is a leading contract research organization serving the needs of biotechnology, pharmaceutical and medical device companies worldwide. The company has a wealth of experience in the execution of global, regional, and local clinical development programs with a special focus on addressing unmet needs in such areas as analgesia, CNS, rare diseases, medical device and diagnostics, and pediatric research. Premier Research operates in 50 countries and employs more than 1,000 professionals, including a strong international network of clinical monitors and project managers, regulatory, data management, statistical, scientific, and medical experts. With its mission to improve productivity in clinical development, the company aligns itself with the mission of its customers to bring new medical treatments to patients promptly, accurately, and cost-effectively.