Dear FDA,

Mom's Favorite Letter-Writing Ink

The following comments were submitted at
https://www.regulations.gov/document?D=FDA-2013-N-0035-0273
in response to the recently issued FDA ALS Draft Guidance for Developing Drugs:



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Dear FDA,

We must not let the FDA issue this Guidance to drug developers!

The draft Guidance document issued on February 18, 2018, does nothing to improve or accelerate drug development for ALS. Instead it institutionalizes the status quo. We cannot afford to do that. It is the definition of insanity.

For decades we have respected the FDA's position that you do not design clinical trials. If people dealing with ALS wanted novel trial designs, a drug developer needed to bring one to the FDA. The FDA couldn't approve or suggest something that was not proposed to them. 

The FDA's draft Guidance document for ALS insures that a novel clinical trial design will not be brought to the FDA.  

"FDA strongly recommends that sponsors conduct randomized, placebo-controlled, double-blind studies. Generally, these studies are the most efficient way to demonstrate efficacy of drugs for the treatment of ALS."

...

"Historically controlled trials for ALS are strongly discouraged."

These recommendations will stifle all innovation to find trial designs that mitigate placebo concerns for dying people or that might actually improve the control groups used to show efficacy.

In addition, you completely ignore possibilities for using technology for better, continuous assessment (removing their concerns about "patient motivation and effort") and which can make the clinical study itself more patient-focused by allowing remote reporting.

If we compare and contrast the ALS Guidance to the final DMD Guidance, we see that ALS got a much less thoughtful document when it comes to measures and effects on patients.

If we compare and contrast the ALS Guidance to the BCG-Unresponsive Nonmuscle Invasive Bladder Cancer Guidance, we wonder why ALS does not raise the same concerns that the cancer document raised about placebo --

"Single-arm trials are appropriate in clinical settings where a randomized, controlled trial is either unethical or not feasible."  

Why would this not also apply to ALS? Why is there not consistency at the FDA between cancer and ALS Guidances?  Do ethics not cross FDA divisions?

“Death” is only mentioned once in the ALS document, and it is in the context of how death can confound trial results.  Death is both cruelly and quickly approaching for every individual with ALS. Why does the guidance ignore the fatal side-effect of ALS itself?

There is nothing in your Guidance draft that will improve the status quo for people with ALS and for drug developers seeking more efficient and more effective paths to drug approvals.  This Guidance would be worse than no Guidance.

Making the status quo the official guidance of the FDA is not acceptable. You could have written this document 40 years ago. Have you no thoughts related to acceptable risk, type 2 errors, trial designs now that there are two FDA approved products, identification of responder subgroups, etc?

 I participated in the FDA ALS hearing five years ago.  Were you not listening, FDA?  We deserve better than this document.

 From your mission: “"FDA is responsible for advancing the public health by helping to speed innovations that make medical products more effective, safer, and more affordable and by helping the public get the accurate, science-based information they need to use medical products and foods to maintain and improve their health.”

This draft Guidance fails to meet your mission.

Sincerely,