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February 29 was the ninth annual Rare Disease Day, when hundreds of industry organizations and patient groups around the world held events to raise awareness about rare diseases and the research that needs to be done to help the millions of patients suffering worldwide.

Rare disease research can be particularly difficult for a number of reasons, but one of the biggest challenges is recruiting. When you are developing a drug to treat a very small population of patients, or a tiny subsection of a larger population, it can feel overwhelming to even imagine how you will set up sites and attract enough patient to make the research work. The truth is, there is no silver bullet, but there are strategies researchers can follow to make this process faster, easier, and a lot less expensive. As we acknowledge Rare Disease Day, I think it is fitting to share this best practice example of how to one big pharma company took a different approach to recruiting, and how it paid off.

Investigate the investigators

We recently worked with a biopharma company that was preparing to launch a Phase I study for patients with an extremely rare form of an already rare disease. The targeted patients, who have a unique gene mutation, represent just two percent of the entire disease population, and the sponsor was uncertain about how to identify and recruit enough patients to support the goals of the trial.

Rather than opening dozens of sites around the world and hoping the right sub-group of patients would turn up, they took a more strategic approach by conducting an in-depth review of all of the literature published about this disease and the specific patient population to identify key opinion leaders globally. The review, which began with a Google search, identified dozens `of investigators whose published work suggested that they were focused on the disease and would likely have access to patients with this specific genetic mutation. The planning team then reached out to all of these investigators to determine who among them had a keen interest in treating patients with this specific mutation -- versus those who’d only experienced a few patients in the broader spectrum of their work. In some cases they found physicians listed on a peer reviewed article who were only accessory authors but who could suggest the best investigators to connect with.

After narrowing the search, they invited the top 20 investigators from around the world to join an innovation team and hone the protocol and recruiting process, and identify as many-pre-qualified candidates as possible. 

Most of these investigators had no experience with trials or trial design but they had been working closely with these patients, bringing valuable insight to the project. By working together, the biopharma research team and the investigators were able to educate each other about what this patient population would want from a trial, and what criteria were required to make the trial results meaningful.

One of the key outcomes of these collaborative conversations was the idea that because these patients were likely to die from the disease before the drug came to market, they would be more open to participating, if they would be given the opportunity to use the drug as an open label prescription, after initial research demonstrated enough safety data to warrant the option. Together, the research team and the investigators created a protocol that met everyone’s needs, and the investigators helped the research team target their recruiting efforts.

This initial research stage took roughly a year, but enabled the biopharma company to recruit patients to the trial much more quickly and effectively than if they had followed a more traditional approach.

A new protocol

This example offers a valuable lesson about the importance of thinking more strategically about the trial design process in rare disease research. It also highlights the benefits of working with key opinion leaders to inform the trial design and to connect with patients who might be eager to participate in a trial designed to ease their suffering.

It requires trial sponsors to set aside additional time at the beginning of the project to identify these investigators and educate them about the trial process. They also must be open to learning from these investigators what patients will need from a trial and how they can improve their protocol to meet those needs. But that time spent up front is more than made up for in savings down the line. If researchers can identify where to find these patients, and connect with them directly through their physicians, they can recruit them more easily, and set up sites that will be most likely to serve the largest number of patients in the shortest amount of time.

This is just one example of how rethinking the traditional trial design methodology can help rare disease researchers overcome some of the barriers to progress. It also underscores how important it is to build a targeted operational strategy and structure for rare disease clinical trial conduct. Careful planning, which may involve moving away from traditional operational models, enhances the opportunity for a unique and successful operational strategy.

Rare disease research is becoming an increasingly attractive development path for biopharma companies around the world. The biopharma companies that are willing to adapt their methods, partner with global experts, and embrace new ideas will be the ones to see the most success in this space.