At $28,000 a Dose, How Effective Is Acthar?

By Jonathan J. Darrow

In a well-researched, recent post, Patrick O’Leary addresses the FDA’s efficacy requirements as applied to an old drug, Acthar (corticotropin), that was first approved in 1952 and granted an orphan designation in 2010 for the treatment of infantile spasms. The initial approval therefore occurred before the Drug Amendments of 1962, which instituted a “new” statutory requirement of efficacy (more on this below). O’Leary points out that Acthar’s “grandfather” status does not entirely exempt it from the FDA’s efficacy requirements, and that the drug did survive an efficacy evaluation under the DESI program. But how effective is Acthar?

Neither O’Leary nor the New York Times article on which his post is based dig very far into the clinical trial data accepted by the FDA as supporting the efficacy of the drug as a treatment for infantile spasms, and I was curious to know what the evidence says about Acthar in this regard. Clinical trial data is presented—or perhaps more accurately, “buried”—in Section 14 of a drug’s FDA-approved label; in the case of “H.P. Acthar Gel” (NDA 022432), that label can be found here. What does the clinical trial data reveal?  The section is brief, just half a page, and notes that of “[t]hirteen of 15 patients (86.7%) responded to Acthar Gel as compared to 4 of 14 patients (28.6%) given prednisone (p<0.002).”  Nonresponders were then given the other treatment, with the following results. “Seven of 8 patients (87.5%) responded to H.P Acthar Gel after not responding to prednisone,” while “[o]ne of the 2 patients (50%) responded to the prednisone treatment after not responding to Acthar.”  As the p-value (0.002) indicates, the first figures, at least, are statistically significant.  These figures were also better than I expected: 86.7% efficacy with Acthar does seem much better than 28.6% efficacy with prednisone.  Continue reading

Where Are We Now: Post 4, Looking in the Mirror, or 3 Games in Public Health

By Scott Burris

In a well-known exchange, Richard Epstein argued that modern public health had strayed far outside its traditional and proper work of preventing epidemics and injuries into a realm of social engineering in which it lacked both competence and legitimacy. William Novak, the historian, disagreed, emphasizing the continuity of our public quest for well-ordered, salubrious (and virtuous) communities. Deciding whether public health is winning or losing in the legal arena – and figuring out how we win more often — depends to some degree on what game it is we think we are playing – that is, on whether Epstein or Novak is right.

I think they both are, and it is worth considering how. I suspect that most of us think, without going too deeply, that we’re doing pretty much the same thing that Lemuel Shattuck was doing at the dawn of modern American public health: marshaling collective resources to use data to diagnose, treat and prevent harm to public health.  And if that’s what you think you’re doing, his report is still an excellent guide to making the case for legal action: evidence shows that we can prevent morbidity and mortality in a cost-effective way that does not significantly interfere with anyone’s rights and makes our society stronger and more competitive.

But law, at least, is a very good area for asking whether we are doing something quite different than our grandmother’s public health.  The use of law as a tool of intervention in public health – as a way of creating safer products and environments and incentivizing healthier behavior — has exploded since the 1960s. Yes, you can find public health law at work in the early 17th century, but when I was born in 1956, there was no OSHA, no EPA, no NHTSA. No warning labels on dangerous products. No safety belt standards or laws. Minimal limits on drinking and driving. No federal clean water or air standards. An unrecognizable FDA. And so on it goes.  In the great Novak-Epstein debate, Novak is right that we have a rich tradition of public health regulation, and plenty of paternalism and interference with individual rights based on epidemiological evidence of preventable harms. This is public health as sic utere, then and now largely a matter of showing how someone is doing something that demonstrably imposes costs on others. That’s why the debate Shattuck was waging sounds so familiar to contemporary ears. (And, by the way, that extends to the moralism implicit in our “scientific” recommendations about healthy lifestyles.)

But Epstein is right, too, I think, to observe that something is different. Public health is now a pillar of the regulatory state and the risk society, deeply enmeshed in the project of defining and minimizing risks great and, let’s face it, small.  We deploy complex regulatory systems, some of which work and some of which we continue to defend anyway, in spite of our own commitments to evidence. As matters like obesity and inequality take intervention further and further from proximate to distal links in the causal chain, our ability to back our proposals with evidence, and evidence that speaks to an everyday sense of causality, becomes severely attenuated. Much of what we propose rests on a vision of the good – salus populi – that is as much a matter of values as it is of evidence.  Failing to own that, we fool ourselves without winning over our audience.

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