Post updated June 28, 2013. See end of post for additional information from FDA.
Five ME/CFS advocates recently sent a letter to DHHS, FDA and select members of Congress requesting that FDA convene a second meeting with ME/CFS patients “to develop a clear regulatory pathway” for drugs to help us. This letter has been followed by a call for patients to email FDA in support of such a meeting. However, both the letter and the email template contain multiple statements that are inaccurate or imprecise. I am concerned that these errors are significant enough to potentially undermine the effectiveness of the letter with the very people it is meant to influence.
Part of my role as an FDA Patient Representative is to bring the ME/CFS perspective to FDA discussions. But another part of my role is to bring accurate information about FDA to the ME/CFS community. It is in that spirit that I point out a few of the errors in this letter and email campaign. I am not trying to micro-edit or nitpick. Rather, I believe that precision and careful crafting of requests can make us all more effective advocates.
The rules should not apply
The email template includes this statement:
FDA has the power and the authority to waive traditional regulations when healthcare demands, particularly when the disease is serious/life-threatening, as ME/CFS clearly is.
No, FDA cannot do this. FDA is one of the most highly regulated agencies in order to make it very clear what FDA can and cannot do. The products that FDA monitors and regulates account for a huge part of our economy. FDA has an extraordinary amount of power, but the regulations exist to constrain that power. FDA cannot look at a situation, wave a wand and say the traditional regulations do not apply. There are alternatives to “traditional regulations,” but those alternatives are themselves defined by more regulations.
No regulatory pathway
The letter sent to FDA and select Congressmen states, “The FDA must create such a regulatory pathway for ME/CFS.” I’m seeing this phrase – regulatory pathway – pop up in multiple places now. While the letter does not say so, I frequently see the phrase used in comparison to AIDS, tuberculosis and Alzheimer’s. To paraphrase the argument: those diseases have special regulatory pathways so we need one too.
But this is not correct. TB and Alzheimer’s do not have their own regulatory pathways. To my knowledge, there are no disease-specific or individualized pathways. There are special programs to accelerate review, and these were discussed at the FDA meeting by Melissa Robb beginning at page 74 of the meeting transcript. These programs include Accelerated Approval, Fast Track, Priority Review, and Breakthrough Therapy. These programs are all defined by regulations, but they do not lower the standard for safety and effectiveness nor are they specific to a single disease.
Where FDA does get disease-specific is in issuing Guidance to Industry. Guidance documents are intended to give FDA’s perspective on a specific issue or disease. For example, the draft guidance to industry on developing drugs for early-stage Alzheimer’s provides FDA’s thinking on the design of clinical trials for this purpose, including selection of patients, selection of endpoints, and ways to demonstrate disease modification. Guidance documents go through substantial processes of development, including a period of public comment. The documents also do not establish legal or regulatory requirements; the guidance is a non-binding recommendation from FDA to industry.
Guidance to industry on ME/CFS was proposed at the April meeting by several people, including Ms. Jody Roth from Eli Lilly. Dr. Theresa Michele, Clinical Team Leader in FDA’s Division of Pulmonary, Allergy and Rheumatology Products – where all ME/CFS drug applications are reviewed – said:
[G]uidance for industry is definitely, I think, an important next step. It’s something that we here at FDA are already thinking about. . . and we hope to be working on that definitely over the next months to a year or so. It takes a long time for a guidance from FDA, just the logistics of getting it through the system. FDA Drug Development for Chronic Fatigue Syndrome and Myalgic Encephalomyelitis: Public Workshop Day 2, April 26, 2013, pp. 339-340.
The advocates’ letter was dismissive of the prospect of a report, saying: “A report of any kind, but particularly one that has no specific deadline, is a very poor outcome for the amount of work that was put forth by the FDA, the experts and, most importantly, this debilitated population of patients.” But there is a significant difference between a summary report of the meeting and a Guidance to Industry document. FDA can’t force drug developers to come into the area of ME/CFS. But FDA can encourage it, and can provide industry with the guidance it needs to design good clinical trials. From what I heard on and off the record at the meeting, FDA is ready and willing to do exactly that. A Guidance report would be an outstanding and much needed outcome from the meeting.
Precision is so important, especially in communicating with FDA. Claiming that other diseases have individual regulatory pathways is inaccurate. I think I know what the advocates mean here: that FDA should clearly state what endpoints and outcome measures should be used in clinical trials, and then shepherd review of products through the various pathways for accelerated approval. But that is not what the letter says, and therefore there is a risk that FDA will not understand that this is what they mean.
May I Have Another?
The fundamental request of the call to action is for FDA to hold a “true” stakeholders’ meeting by the end of the year to define a regulatory pathway for ME/CFS treatments. But why would FDA agree to hold another meeting when we’re only sixty days out from the first, especially when the meeting comment docket has not closed yet? While the letter cites numerous criticisms of the April meeting, it seems to ignore that requesting a second meeting so soon after the first and in this fiscal climate is extraordinary, and therefore a compelling case must be made in support of that request. I fear that the errors and imprecision in this letter and email campaign undermine the attempt to make a sufficiently compelling case.
Effective communication requires understanding the context and language of the audience. If we are imprecise or inaccurate, the audience will get distracted by our mistakes and lose sight of what we are actually trying to say. In turn, this can lead to the failure of the overall communication through misunderstanding or even outright dismissal. FDA’s language is based on statute, regulation and science. The errors I discussed are potential signals to FDA that we do not actually understand what the agency can do or the best ways FDA can help us.
ME/CFS advocates require the same of others. How do we react when someone says “chronic fatigue” instead of “chronic fatigue syndrome”? Or “CSF” instead of “CFS”? We expect clinicians, researchers and agency representatives to know our issues and our language. We all know the difference between the Oxford definition and the Canadian Consensus Criteria, and we justifiably react negatively if someone tries to tell us those definitions are basically the same thing. To communicate effectively with us, an agency representative would do well to be precise and accurate. Otherwise, we end up reacting to the mistakes in the message and the actual message gets lost.
To be effective advocates, we must also be precise and accurate and we undercut our own position if we fail to do so – even if the failure is accidental. I know the advocates who have called for this action, and have worked with them in the past on other efforts. Each of them is deeply committed to advancing the cause of ME/CFS patients. But as advocates, we have a responsibility to communicate as clearly and effectively as possible. It is worth the time and energy invested to craft a specific, accurate and strategic request that speaks to the context of the audience. Such a carefully crafted request focuses discussion on the substantive issue, rather than accidentally diverting attention with misstatements.
We owe it to each other and the ME/CFS patient community to get things right. We must speak with precision and clarity about complex topics, while also presenting a strong case for what ME/CFS patients need. It is not an easy thing to do, but it is essential to our collective and ultimate success.
Update June 28, 2013: After some discussion in the comments, I asked FDA whether the April meeting was sufficient to begin the Guidance to Industry process, and whether FDA would be pursuing it. Dr. Theresa Michele replied via email to me, in part:
With regards to the guidance for CFS—yes, we are working on it. The April meeting was an excellent starting point. Please be aware that the guidance process takes many months of internal writing and editing before anything is posted, since multiple groups at FDA have input into all guidances. During this process, we will continue to take into account any new information that becomes available, such as the CDC study and the NIH Evidence Based Methodology Workshop. Once the guidance posts, it will be considered a “Draft Guidance” and FDA will take into account any comments we receive from the public before publishing a Final Guidance, usually several years later.
In the meantime, industry is not without recourse—the Division of Pulmonary, Allergy, and Rheumatology has made it very clear that we are extremely open to granting development meetings to any sponsor interested in developing products for ME/CFS. (emphasis added)