ALS, the Rule of Rescue, and the FDA

The opening paragraph in "Fighting for a Last Chance at Life" in today's New York Times led me to expect what the Brits call "hanging crepe" - using imminent death to blast insurers as uncaring, profit-seekers and the FDA as a callous bueaucracy:

As Lou Gehrig’s disease sapped Joshua Thompson of his ability to move and speak last fall, he consistently summoned one question from within the prison of his own body. “Iplex,” he asked, in a whisper that pierced his mother’s heart. “When?”

Joshua, a vigorous, athletic, married 34 year old father was diagnosed with Amyotrophic Lateral Sclerosis in 2007. Kathy Thompson, Joshua's mother went onto the web, and learned about Iplex, a drug containing an insulin-like growth factor that in 2006 had been reported to stimulate growth of the nerve cells involved in ALS (in tissue culture). The growth factor had been tested on ALS patients and was found to be ineffective, but Iplex combined the growth factor with a protein that might get it into the nervous system more effectively. The New York Times article describes in rich detail the campaign Kathy orchestrated to make Iplex available, despite the lack of FDA approval or evidence - other than anecdotes from Italy, where the government provides it - for its effectiveness.

There are currently no effective treatments for ALS. It is regarded as a uniformly fatal condition. The desperate effort on the part of ALS patients and their families to try any approach about which they have hope is totally understandable. The public policy challenge is - how should a health system respond to patients in a "last chance" situation who want medications (or other interventions) they regard as promising but which have not been shown to be effective?

It's possible that the medication may prove to do more harm than good, but I don't see that as a reason to forbid access. As Kathy Thompson said when safety concerns were invoked - "what, exactly, is safe about ALS?" Patients who are competent to make decisions and who are fully informed about the risks and benefits of a treatment are entitled to decide whether they want to bear the risks for the chance of the gain.

The core issue involves considerations of the common good. If unproven medications are made available, patients in last chance situations will want to try them. I know that I would. But when this happens it is impossible to find out whether the medication really works. In the 1990s many states mandated insurance coverage for high dose chemotherapy and bone marrow transplant for women with advanced breast cancer. The availability of the treatment made it almost impossible to test its effectiveness. When results finally came in it emerged that the treatment was no better than the existing interventions, and often worse. Hundreds of millions of dollars were spent for what, on a population basis, was a net decrement in health compared to alternatives. (The chemotherapy story is told in detail in False Hope.)

As I read the story I thought - the FDA should make the drug available for what is called "compassionate use," but only in the context of a clinical trial. To my surprise and pleasure, that's exactly what the FDA did in March of this year. Here are the key sections of the FDA statement:

FDA's Decision

The FDA and Insmed [the manufacturer of Iplex] have agreed that access to Iplex for investigational use in patients with ALS will occur in two ways under Investigational New Drug applications (INDs):
1. Single-patient INDs requesting “compassionate use” of Iplex for treatment of named patients with ALS, received and date-stamped by FDA’s document room by close of business on March 6, 2009, will be allowed to proceed, and Insmed has agreed to supply Iplex to those patients; and
2. The remaining supply of Iplex, which is very limited, will be used by Insmed to conduct a clinical trial under an IND in which other patients with ALS who are interested in receiving Iplex treatment will be randomly assigned to receive drug through a lottery system.
All patients who receive Iplex under either a single-patient IND or in the Insmed clinical trial must be adequately informed by their treating physician of the possible benefits and risks of the treatment...

Rationale for FDA's Decision

...FDA has attempted to balance the needs of individual patients who are desperately seeking treatment options for this devastating disease with the need to learn if the drug is in fact beneficial, or harmful, in treating patients with ALS. These considerations were weighed over the last few weeks by FDA scientists and physicians, who held a series of meetings with Insmed and internal meetings to discuss the best path forward.

Conclusion

The FDA understands that ALS is a fatal disease with limited to no treatment options. We are very sympathetic to the desperate situation of patients with this terrible disease, and their families, and we remain committed to facilitating the development of effective drugs to combat ALS. Sometimes therapies that appear promising in the preclinical phase (before studies in humans) do not lead to benefits in patients...

The FDA is mindful of the need to strike a balance between access to unproven therapies for patients with limited treatment options, and the ethics of subjecting those patients to drugs with unacceptable risks or unconfirmed benefits. Today we have chosen a means to provide access to Iplex to as many patients as possible, consistent with all of the considerations discussed earlier.

The FDA has done an impressive piece of ethical analysis with regard to Iplex and ALS. It recognizes the dire circumstances of people like Joshua Thompson in last chance situations, the intensity of society's wish to rescue identifiable victims, and the importance of rigorous evaluation of new treatments on behalf of the common good. Hat's off to the FDA!