‘Interventional pharmacoeconomics’ debases drugs and pharmacology alike


July 16, 2019

A Letter to the Editor of JAMA Oncology, desk-rejected July 15, 2019:

To the Editor: The Viewpoint by Drs. Ratain, Goldstein and Lichter1 advances a program of ‘interventional pharmacoeconomics’ (IVPE) founded on one of several cognitive distortions described by Greenland: “nullism, the tendency to privilege the hypothesis of no difference or no effect when there is no scientific basis for doing so.”2 IVPE aims to reduce drug exposure while yet “maintaining [equivalent] efficacy.”1 This incantation repeats—with ‘equivalent’ deftly elided after its initial appearance—fully 8 times throughout the Viewpoint. But its repetition ought not dull our senses to the fact that it espouses an outright exposure-response denialism. Remarkably, the authors make no secret of their intention to deploy the absence-of-evidence fallacy in prosecuting this case: When they speak of “several of the new checkpoint inhibitors for which there is little or no evidence of a relationship between dose and efficacy,” they recall unmistakably Braithwaite’s there-is-no-evidence-to-suggest.3

One might like to imagine such denialism banished to the province of homeopathy, but sadly this type of thinking has long hobbled even mainstream clinical drug evaluation.4 Still, it will only frustrate needed progress if we endorse such pharmacologic nihilism anew, in the guise of this fresh-faced field equipped with its shiny acronym plus the ample underwriting likely to accrue to a “discipline” preening itself as a servitor to corporate and government payors. Substantive scientific probing of exposure-response relationships will require the intellectual invigoration of clinical pharmacology, not its debasement to the level of financial spreadsheet analysis.

The only remedy for this looming folly would seem to be calling IVPE what it is. I suggest the term ‘drug sweating’, by analogy with the method of debasing coins by shaking them in a bag so as to recover precious-metal dust, while maintaining the ability to pass them on at full value. If this program of drug sweating prevails, then our drugs and clinical pharmacology as well will emerge worse for wear.

My main hope for IVPE would be that it does not achieve its overtly stated aims, but instead forces industry to abandon per-milligram drug pricing altogether, in favor of per-patient licensing. Such licensing seems indispensable for equitably achieving dose individualization, which in turn appears fundamental to the enlightened pursuit of optimal social value from pharmaceutical innovation.5


1.  Ratain MJ, Goldstein DA, Lichter AS. Interventional Pharmacoeconomics—A New Discipline for a Cost-Constrained Environment. JAMA Oncol. June 2019. doi:10.1001/jamaoncol.2019.1341

2.  Greenland S. Invited Commentary: The Need for Cognitive Science in Methodology. Am J Epidemiol. 2017:1-7. doi:10.1093/aje/kwx259

3.  Braithwaite R. EBM’s six dangerous words. JAMA. 2013;310(20):2149-2150. doi:10.1001/jama.2013.281996

4.  Sheiner LB. The intellectual health of clinical drug evaluation. Clinical Pharmacology and Therapeutics. 1991;50(1):4-9. doi:10.1038/clpt.1991.97

5.  Norris DC. One-size-fits-all dosing in oncology wastes money, innovation and lives. Drug Discov Today. 2018;23(1):4-6. doi:10.1016/j.drudis.2017.11.008