By Richard S. Bedlack, MD, PhD
"Curiouser and curiouser," said Lewis Carroll's Alice as she experienced Wonderland. The same words keep running through my mind as I consider certain aspects of amyotrophic lateral sclerosis (ALS). It is perhaps the most devastating of all diseases, causing rapid and progressive loss of speech; difficulty in swallowing, breathing, and performing voluntary limb movements. Despite 130 years of research, ALS remains incurable.
Yet we are making progress. Symptomatic care for patients with ALS (PALS) has markedly improved, in large part due to the formation of specialized, multidisciplinary ALS clinics.1 Also, the pipeline of potential disease-modifying therapies being tested in ALS clinical trials is more impressive than ever. Given this background, it seems obvious that most PALS would attend specialized ALS clinics and participate in clinical trials—but this is not happening. Fewer than 50 percent of PALS in North America ever receive care in a specialized ALS Clinic. Within specialized clinics, only 5 to 25 percent of PALS participate in an ALS research study.2
Over the past few years, I have tried to understand and affect the above problems. I wish I'd listened sooner to Carroll's doorknob quote: "Read the directions and directly you will be directed in the right direction." My early efforts, though passionate, were not always organized. Eventually, with the help of the 2008 Palatucci Advocacy Leadership Forum, I was able to develop a mission statement:
To influence opinion—and to change behavior and policy in ways that optimize access to and enrollment in ALS research—I started a new "Advocacy Subcommittee" within the National ALS Research Group.3 With the help of my Palatucci and ALS Research Group colleagues I generated four specific aims:
We are making significant progress on each of these aims.
We have developed an online survey for PALS to better understand their knowledge and collect their opinions of our specialized clinic. This is currently enrolling via a number of websites.
While we await this data, we have acted upon the two most likely reasons that so few PALS are coming to our clinics: either they or their referring physicians don't understand the benefits of these clinics, or there aren't enough clinics. To target the first of these, I developed a slide set highlighting the benefits of specialized ALS clinics, which I use as I travel the country speaking to PALS and potential referring physicians in various settings. In the past two years, I have used this in more than 30 talks. I also made it available to colleagues online for their use in other parts of the country.4To attack the second possible reason for low attendance in clinics, I studied my state's population density map and identified an apparently underserved area: Greenville, NC. I travelled there and met with local families affected by ALS, with the leaders of the hospital, and with potential local ALS team members including local neurologists, physical therapists, occupational therapists, speech therapists, nutritionists, respiratory therapists, psychologists and social workers.
With regard to increasing enrollment in ALS research studies, a meta-analysis we conducted last year suggests that the designs of our studies have very little to do with influencing enrollment; this means that "patient factors" and "doctor factors" may be the primary determining factors.2 We plan to use the online survey of PALS described above to learn about their attitudes and opinions regarding ALS research studies.
Meanwhile, we conducted a retrospective survey of colleagues at other North American ALS clinics, and with this identified potentially modifiable behaviors that we as physicians could use to help our own cause. These include a more enthusiastic attitude toward our studies and better education, targeted toward PALS, delineating the benefits of participating in research studies and the dangers of pursuing alternative options.
We also have two new research protocols underway for increasing enrollment in ALS research studies. In the first, we will prospectively track enrollment decisions across all studies in North American ALS clinics to be sure this data agrees with information obtained retrospectively. We will do this before and then again after we start using an educational brochure for PALS that describes the benefits of participating in research. In the second protocol (to be used within an active trail), we will randomly distribute a video which will explain the study rationale and procedure. This will be used to supplement the consent process. By the end of 2009 we hope to know whether either of these interventions can positively influence enrollment.
We and others independently demonstrated that approximately 50 percent of PALS pursue an alternative therapy in lieu of participating in research.2,8 We plan to use the online survey of PALS to better understand this. While awaiting our survey, we have developed a number of educational materials targeted toward PALS and toward colleagues directing ALS clinics. These include another slide set for PALS that explains different types of scientific evidence, the dangers of specific alternative therapies such as chelation and treatment of seronegative Lyme, and how to evaluate new alternative options. I have used this in several talks, as well as making it available online for colleagues to use when they speak to PALS around the country.9
We recently published a book chapter for PALS that follows these slides.10 We have also written editorials outlining cautions and discussion points for my colleagues on two off-label ALS therapies that many PALS are asking about: lithium11 and mecasermin rinfabate.12 Currently, we are working on a plan to publish systematic, quarterly scientific reviews of the most discussed alternative and off-label options that PALS are asking about in our clinics and discussing in online chat rooms.
Finally, we have met with all my North Carolina Congressmen over the past year as part of National ALS Advocacy Day 2008. Colleagues and PALS came from across the nation to ask members of Congress for three things, all relevant to my mission statement:
Within a few months of our visit, all of these passed both houses of Congress and were signed by the President.
While we are clearly moving toward fulfilling our mission statement and specific aims, we still have far to go. As Carroll's King said, "Begin at the beginning, and go on till you come to the end; then stop." I remain passionate and enthusiastic that we can help PALS find multidisciplinary clinics and research studies so that their burden of ALS will be minimized, and so that we can all make the fastest possible progress with our research toward the ultimate end: a cure for ALS. I won't stop until we get there.
Within the past 24 months, Dr. Bedlack received personal compensation from Lilly and Pfizer for speaking, and he receives a yearly grant from the ALS Association, which helps in his work with ALS clinics. In the same period, he has acted as a witness in a legal proceeding. Dr. Bedlack has also received research support from UCB Pharma and the US Department of Defense within the last five years.