Speeding the Development of New Therapies for Patients

Inside the Massachusetts General Hospital’s neurology department is an uncommon resource for clinical investigators. The Neurological Clinical Research Institute (NCRI) is a contract research organization that runs clinical trials for investigators both inside and outside of Mass General.

But the ultimate goal of NCRI is to speed the development of drugs for neurological disorders. So far, with the help of exciting initiatives in information management and the coordination of research networks, it is meeting that goal.

“The NCRI isn’t a secret, but it’s not well-known that we have this great strength here,” says Dr. Merit Cudkowicz, chief of Neurology and NCRI co-director. “We’re bringing scientists, clinicians, patients and families together so that we can bring new drugs to patients as efficiently as possible.”

Founded in 1994, NCRI has amassed a track record of successes using its resources and infrastructure to launch new clinical trials. While NCRI helps many, it is of particular value to researchers with exciting leads for potential new therapies, but no experience moving those ideas into testing.

For instance, one bench scientist at Mass General with no trial experience wanted to begin testing a novel drug for amyotrophic lateral sclerosis (ALS). With NCRI’s help, his trial is now enrolling patients at ten centers across the United States. Such assistance is available to researchers outside of Mass General, too. “We can help them develop a protocol, get funding, and get the therapy into a patient trial,” says Cudkowicz.

The Power of Shared Data

Beyond helping individuals and small groups get trials off the ground, NCRI has also launched several initiatives for sharing data. These initiatives, called PRO-ACT, PharmaEngine and NeuroBANK™, are increasing the power of data collected through clinical trials, clinical research and patients’ hospital visits.

Data about patients and their diseases is critically important to researchers trying to understand neurological diseases. But all too often, data collected during trials remains hidden inside isolated databases or investigator filing cabinets. For diseases that are considered rare, such as ALS, isolated databases don’t contain enough information to shed light on the disease and how it progresses.

So in 2011, Alex Sherman, Director of Systems at NCRI, in collaboration with Prize4Life and the Northeast ALS consortium (NEALS), created a shared database called PRO-ACT, which stands for The Pooled Resource Open-access ALS Clinical Trials. Many biotechnology and pharmaceutical companies and academic institutions around the world contributed data to this initiative, which now contains nearly 11,000 de-identified patient records.

Using this data, analysts have been able to create algorithms that predict disease progression. One predictive model has proved so powerful that it is currently under consideration for use in clinical trials to reduce sample size and speed up the drug approval process. “If this approach works, if we can predict how a patient’s disease would progress without the drug using this model, we might be able to lower the cost of clinical trials by reducing the size of placebo arms,” says Sherman.

For research projects in the pre-clinical trial phase, NCRI developed NeuroBANK™, a patient-centered platform for the collection and sharing of patient data for trials. NeuroBANK™ links data about an individual patient across multiple trials and also links patient records to medical images, genetic data and tissue repositories.

Researchers designing neurological clinical research studies can choose to use NeuroBANK™ instead of creating their own database, speeding the development of the trial. In addition to being a valuable resource for data sharing, says Sherman, “we look at it as an accelerated research environment.”

The Power of Research Networks

Five years ago, the National Institutes of Health launched NeuroNEXT, a network for excellence in neuroscience clinical trials. The network consists of twenty-five centers across the US, the NCRI, which coordinates clinical trial operations, and the University of Iowa, which coordinates data and statistical analysis.

The goal of the network was to efficiently conduct seven high-impact phase II trials over seven years. Five trials are in progress today, and two more will start this year.

The network has vastly reduced the time it takes a trial to get off the ground. In the past, once funded, a trial might take another year to enroll the first patient. “There was a lot of duplication of effort,” says Cudkowicz, particularly in terms of ethical reviews and contract negotiations.

In contrast, NeuroNEXT sites have agreed to one ethics approval process and a single master contract. This cooperative effort has, on average, reduced the time from funding notification to first patient enrollment from up to one year to about three months.

The work of NeuroNEXT also translates into real gains for patients. In the four studies NeuroNEXT has started enrolling, all have met their recruitment goals or are on track to meet them, including one trial that recruited infants less than six months of age with a rare disease called spinal muscular atrophy. “Everyone said it would never recruit enough people, but we completed recruitment ahead of schedule,” says Marianne Chase, Director of Research Operations at NCRI.

This, it turns out, is not common. Many clinical trials never recruit enough people to come to a conclusion about whether a drug is worth continued investment or not. “Our initiatives at NCRI are all about lowering the barrier to developing the best treatments for our patients,” says Cudkowicz.

For more information, please visit the NCRI website.