Alex Philippidis Senior News Editor Genetic Engineering & Biotechnology News

Registries connect patients with advocates, clinicians, and drug developers.

The “Father of Modern Medicine” is also the father of patient registries. Hippocrates (c. 460 BC–c. 370 BC) urged doctors to record the symptoms they observed daily in their patients: “The physician must be able to tell the antecedents, know the present, and foretell the future.” (Of the Epidemics, c. 400 BC).

The first modern registries, focused on patient populations with specific diseases, emerged in the 20th century, with their use expanded for disease- and drug-based research by the 1980s. Now, in the age of Big Data, the registries give new meaning to community organizing by growing, or planning to grow, into sources of some of the most valuable data around—namely, the experiences of patients, and the genetics behind them.

Among the latest registries to launch is one by a research partnership focused on better understanding the importance of mutations and variants, including variants of unknown significance found by multigene testing for hereditary cancer. Ambry Genetics has joined institutional partners—including the diagnostic testing labs of Memorial Sloan Kettering Cancer Center (MSKCC), Mayo Clinic, Abramson Cancer Center of the University of Pennsylvania, and Dana-Farber Cancer Institute—to create the Prospective Registry of MultiPlex Testing (PROMPT).

The partners are developing an online registry for patients who have undergone hereditary cancer testing. PROMPT is open to anybody who has had a hereditary cancer multigene panel test through any laboratory. Results go directly to a clinician, who passes the information on to the patient. Enrollment in the registry occurs directly through the patient rather than via coordination from the provider.

“That’s a new model as well, because the majority of registries that we [hereditary cancer genetics clinics/researchers] have done in the past have been clinician-driven consent processes and so forth, rather than patient driven,” Jill S. Dolinsky, RN, MS, CGC, Ambry’s senior manager of clinical research, told Clinical OMICs. “The answer to why registries are needed is so we can study people with mutations and variants of unknown significance in these genes and better understand how they impact medical management, but the reason such a large, nationwide registry was necessary for PROMPT also has to do with the diversity in laboratories running and clinicians ordering testing now compared to the 1990s.”

The migration of genomics into the clinic not only led to more genetic testing, but to more testing outside large academic centers by community providers.

“We want to gather a whole bunch of families that have mutations in rare genes together in one place with permission for re-contact, so that we can then go back to those families, and say, ‘Alright, now what we want is to do is collect samples from your family members, send them to this researcher who’s interested in doing this work, and calculate out in aggregate what the risks are for, say, RAD51C,’” Mark E. Robson, M.D., clinic director of the clinical genetics service at MSKCC, told Clinical OMICs.

While PROMPT’s first phase focuses on building infrastructure, he said, it will grow over time to enable research into variants of unknown significance, and mutations that hold potential for raising the risk of cancer.

Dr. Robson cited a recent study quantifying the risk of breast cancer for female PALB2 carriers, as compared to the general population—eight to nine times as high among those younger than 40 years of age, six to eight times as high among those 40 to 60, and five times as high among those older than 60. This study, which was published online August 7 in the New England Journal of Medicine, made it possible to assess 362 members of 154 families for PALB2. It was co-authored by no fewer than 48 researchers.

“If you look at the PALB2 paper, fundamentally that’s what we’re trying to do. We’re just trying to do it faster,” Dr. Robson said. “In theory, anybody with access to an Internet connection could say, ‘Yes, I recognize that the scientific community doesn’t know what to do with a BARD1 mutation. My family has a BARD1 mutation. I want to contribute to the effort to figure out what this means.’”

“Instead of relying on academic centers to contribute all their data into some central place, we’re trying to go directly to the people who have the mutations, and ask them to join up and help the effort,” Dr. Robson added.

PROMPT is among registries managed on behalf of research partnerships, patient advocacy groups, and biopharma companies through the CONNECT platform of PatientCrossroads. Through CONNECT, the company also offers access to registries for 300+ conditions, with a combined enrollment of some 60,000 patients. Registries that are managed for clients include more than 50 patient groups, more than a dozen drug developers, nearly a dozen research institutions, and the NIH—for which PatientCrossroads runs the National Down Syndrome Registry.

“Being able to find other people and understand what treatments they’re using, what works, what didn’t work, is very beneficial to the community,” Kyle Brown, PatientCrossroads CEO and founder, told Clinical OMICs. “We don’t let people contact [patient registrants]. This isn’t a social network. But they could certainly see the charts and graphs of everyone else.”

Advocacy organizations can have their patients use the registries at no charge. Funding for PatientCrossroads comes from biopharmas seeking to access the registries as sources of patients for clinical trials on drug candidates. Industry clients include pharma giants such as AstraZeneca, Eli Lilly, Merck & Co., Novartis, Pfizer, and Shire.

PatientCrossroads began as “Facebook for researchers,” Brown recalled, until leaders within the Duchenne muscular dystrophy community, led by Parent Project Muscular Dystrophy (PPMD), began discussing an information portal that would link patients, their families, friends, and caregivers to information on medical research, clinical care, and clinical trials. The result was DuchenneConnect, a pioneering patient-report registry focused on Duchenne and Becker muscular dystrophies and launched by PPMD in 2008 (see “The Making of a Model Patient Registry” below).

Today PPMD is one of more than 50 patient-advocate clients of PatientCrossroads. Another client is the American Partnership for Eosinophilic Disorders (APFED). It has drawn more than 2,000 registrants to the patient registry it launched more than a year ago.

“One of the problems with the medical literature for some rare diseases is that the people who are going to the major academic centers to get helped tend to have more severe forms of disease, so that much the literature that’s published is based on a phenotype that’s more severe than might be seen in the community,” APFED president Wendy Book, M.D., told Clinical OMICS.

“One of our main goals was to capture the larger number of patients who are seen in the community and get a sense of the true phenotypic spectrum,” Dr. Book added. “We wanted to get a broader view to ensure that we could really get at the issues that are important to the patient community at large, not just academic researchers at, say, a tertiary center.”

Another important purpose for APFED’s registry is ensuring it can contact large numbers of people with eosinophil-associated diseases for future clinical trials.

APFED is among the patient advocacy groups working with the Consortium of Eosinophilic Gastrointestinal Disease Researchers (CEGIR), an organization created through a five-year, $6.25 million NIH grant awarded earlier this month to expand the Rare Diseases Clinical Research Network. The consortium will research eosinophilic and allergic disorders and train investigators in conducting clinical research.

Over time, APFED hopes to use the registry to survey patients for information about specific diseases that could help guide future clinical trials.

Let’s say “company A is interested in drug X” and wants to identify the important side-effects and outcomes as well as the patients’ expectations, Dr. Book proposed. “It’s a great opportunity to survey the patient perspective, and have a large number of responses from a broad patient base very quickly.”

The Making of a Model Patient Registry

DuchenneConnect, a pioneering patient-report registry focused on Duchenne and Becker muscular dystrophies and launched in 2008 by the Parent Project Muscular Dystrophy (PPMD), has emerged as a model for developing, using, and growing patient registries.

The registry emerged after leaders within the Duchenne muscular dystrophy community and PPMD began discussing an information portal that would link patients as well as patients’ families, friends, and caregivers to information on medical research, clinical care, and clinical trials.

“We wanted to do anything we could to 1) speed up the research process and 2) make the space as appealing and accessible as possible for clinical trial sponsors and other clinical researchers,” Holly Peay, MS, CGC, PPMD’s director of DuchenneConnect, told Clinical OMICs.

As of September 30, DuchenneConnect had 3,287 registrants—people with Duchenne and Becker muscular dystrophy as well as carriers. About 60% of patients registered are under age 17, reflecting the life-limiting nature of the diseases—as well as high interest in clinical trials among families of younger children, said Peay, who is also PPMD’s vp, education and outreach.

DuchenneConnect relies on reports generated by patients themselves or their parents. “There are limitations to that, but there are also strengths, because there’s a lot of interesting information that we can get from the patient that has nothing to do with their clinical encounters,” Peay continued. “It’s really more day-to-day experience of having the disease.”

Soon, clinicians will also be able to contribute data. The registry’s platform and functionalities were created through collaboration between PPMD and the platform’s developer PatientCrossroads—which has developed an enhancement allowing doctors to contribute a missing piece of data to patient self-reports, such as forced expiratory volume or forced vital capacity.

Data from the registry is being used by drug developers for clinical trials. Dialogue with companies comes as they start planning trials, sometimes years before the first patient is dosed. Relevant questions include whether enough patients exist in an age cohort or geography, how best to inform potential patients, and which clinics would be best able to carry out the study. PPMD’s Certified Duchenne Care Center Program designates clinics whose care meets top standards.

“A company came to us a couple of months ago, and asked whether the ability to do some of the dosing at home would actually be seen as a benefit to families, or an additional burden,” Peay related. “We can find that out. We can ask a number of families about that and get their perceptions. We give feedback on feasibility. We give feedback on the protocol: Is the protocol burdensome? Are there things they can do to reduce the burden? We look at their recruitment materials frequently, and try to make sure that they’re going to be understandable to the community.”

DucheneConnect is one of 18 patient advocacy-created registries that have joined 11 clinical data research networks based at healthcare systems to form PCORnet, a national coalition of networks formed to support the conduct of clinical outcomes research. PCORnet is being funded with more than $100 million from the Patient-Centered Outcomes Research Institute (PCORI), a private, nonprofit organization created by the Affordable Care Act.

In February, DuchenneConnect received $970,000 from PCORI toward enhancements, under a collaboration with PatientCrossroads, Geisinger Health System, and UCLA’s Department of Human Genetics, a partner with the registry in comparative outcomes research since 2011.

Work will include gaining patient feedback on the registry and research priorities, adding new technologies for easier registration and data updating, and exploring if and how the registry can access data from patients’ electronic health records. “We’re somewhat optimistic that for at least a good subset of our patients, we’ll be able to offer that capability within the next couple of years,” Peay noted.

This article was originally published in the November 5 issue of Clinical OMICs. For more content like this and details on how to get a free subscription to this digital publication, go to

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