NEALS: Sharing Among ALS Researchers and Participants

See also Part 1, Part 2, and Part 3.

In the world of neurodegenerative disease trials, no researcher can afford to be an island. Willing participants—particularly with a rare disease such as amyotrophic lateral sclerosis (ALS)—are scattered so sparsely across the country that any one clinic cannot hope to recruit sufficient numbers. The scientific community in general is increasingly realizing that it is all about collaboration, said Michael Benatar at the University of Miami Miller School of Medicine. Benatar is one of more than 140 ALS investigators who are members of the Northeast ALS Consortium (NEALS) (see Part 1).

NEALS was founded so that researchers, working together, could complete more and better clinical studies than they could alone. From the start, anyone with an interest in ALS, and a trial-capable clinic, has been welcome to join. Because NEALS has spread beyond its New England roots—there are now member sites across the U.S. and in Canada and Europe—some members joke that the NE actually stands for Non-Exclusive. But the sharing does not stop there. Scientists can access six datasets from past trials and obtain biofluid samples from NEALS’ growing repository. Non-members pay a $1,000 administrative fee for these resources.

NEALS’ newest initiative is to share its expertise with patients. With recruiting trial volunteers a big challenge in the field (see Part 2), NEALS hopes that educating people with ALS about the process of clinical research will inspire them to participate. This year’s annual NEALS meeting, to be held 26-28 October 2011 in Clearwater Beach, Florida, convenes not just doctors and scientists, but also 10 patient-caregiver pairs. These 20 people will attend the inaugural Clinical Research Learning Institute, a one and a half-day retreat where clinical researchers will teach them the ins and outs of clinical trials. They will address questions such as these: Why does the research take so long? What rules do scientists have to follow? NEALS is co-developing the program with the ALS Research Group—another consortium dedicated to improving patient education and care, as well as supporting research—and the retreat is sponsored by the ALS Association.

After the retreat, the 20 participants can share what they have learned with the larger ALS community, serving as informal ambassadors to promote trial participation. We are trying to generate a buzz, said Richard Bedlack, who heads the ALS Research Group and the Duke ALS Clinic in Durham, North Carolina. These NEALS ambassadors might write letters to the editor and lobby Congress, he said. They might also blog, or participate in support groups, and point their peers to NEALS as a source of information, added Breen Power, NEALS’ marketing and outreach manager at Massachusetts General Hospital (MGH) in Boston. Merit Cudkowicz, NEALS’ co-founder at the hospital, said she is also looking forward to hearing from people with ALS about what keeps them from joining trials.

In November, the NEALS website will launch an updated version intended to serve as an information hub for patients, Power said. Recently, the consortium defined a position for an ALS Trial Expert. This new hire will get up to date on all trials, serve as a patient liaison to companies testing ALS treatments, and as a go-to person for patients’ questions. Once trained, this person will answer the group’s new trials expert hotline, 877-458-0631, or alstrials@partners.org, replacing a clinical research fellow who is a NEALS member at MGH. The lines have been pretty busy, Power wrote in an e-mail to ARF. We have been getting great feedback [from patients who call in].

Explaining trial rules to patients and helping them understand their options are new aspects of NEALS. The consortium already has a track record of sharing information among ALS investigators, such as for de-identified data from past NEALS trials of topiramate, celecoxib, creatine, coenzyme Q10, lithium, and arimoclomol.

Researchers reanalyze data from these past trials, which are available subject to approval by a NEALS committee, to yield new results. For example, Cudkowicz and colleagues plumbed placebo numbers to discover that people with ALS today are living longer than they did in the past. However, muscle strength, lung capacity, and ability to perform daily activities have remained unchanged over the past decade. The researchers concluded that the increased survival is due to intensive symptom management in the later stages of disease—for example, ventilation and feeding tubes—while the underlying disease course has not slowed (Qureshi et al., 2009).

Some members of the same team also mined the archived records to discover factors that might help determine a patient’s prognosis. People with ALS who took aspirin, who had low blood chloride levels, or high blood bicarbonate levels died sooner than average. Those who took calcium supplements fared better than others who did not (Qureshi et al., 2008). Given the effects of aspirin, the study authors suggested that researchers should continue to study the impact of neuroinflammation in ALS. The immune response appears to be a key player in the disease. Although its role—as both protector and mediator of damage—remains far from clear (e.g., see ARF related news story and ARF news story on Chiu et al., 2009), scientists are already pursuing treatment options related to inflammation (see ARF related news story on Lincecum et al., 2010 and ARF Webinar).

The next step, Cudkowicz said, is to convince companies to share their data, too. This is a project called PRO-ACT, for Pooled Resource Open-Access ALS Clinical Trials database. Unlike the six individual datasets currently shared by NEALS, PRO-ACT will unite records from several trials into one pooled database. Spearheading this collaborative project is Melanie Leitner of the Cambridge, Massachusetts-based nonprofit Prize4Life. Prize4Life’s mission is to stimulate ALS research by offering prizes for achievements such as the discovery of biomarkers and treatments (see ARF related news story and ARF related news story), as well as by developing initiatives such as the ALSGene database. (Prize4Life collaborates with ARF on ALSGene and also funds this reporter’s position.)

With PRO-ACT, Leitner and NEALS’ director of systems Alex Sherman will design a data management system to merge and house raw data from Phase 2 and 3 industry trials, together with the NEALS datasets. Leitner estimated the database will contain 5,000-10,000 unique patient records. PRO-ACT’s integrated database can be used for identifying new biomarkers, providing insight into the natural history of the disease, as well as potentially providing insights into the design and interpretation of future clinical trials, she wrote in an e-mail to ARF. Obtaining the placebo numbers alone could be helpful, Cudkowicz said. The ALS Therapy Alliance provided a grant to Prize4Life to support the PRO-ACT project.

In addition to the past trials database, researchers can also apply for access to a collection of more than 4,000 vials of biological samples—serum, plasma, whole blood, cerebrospinal fluid, urine, and DNA—collected as part of NEALS studies (Sherman et al., 2011). Collection, processing, and storage of the samples—many of which stem from NEALS’ biomarker efforts (see Part 3)—are standardized. Many of the samples are stored at Mass General’s Neurology Clinical Trials Unit, while others are scattered in labs across the country.

Part of NEALS’ spirit is to support newcomers. I came into the field almost a decade ago; I did not have a mentor, Bedlack recalled. NEALS was incredibly welcoming to a new, enthusiastic, but rather naive investigator. Like so many NEALS members, Bedlack received personal mentoring from Cudkowicz and NEALS’ co-founder Jeremy Shefner of the State University of New York (SUNY) Upstate Medical University in Syracuse. Bedlack, who credits their advice for advancing his career, now tries to pay it forward by mentoring other researchers. Working with ALS doctors and scientists has been a career highlight, Bedlack said: I am inspired every day in this field.

This concludes a four-part series. See also Part 1, Part 2, and Part 3.


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