"The Warmth of His Continuing Interest": Henry K. Beecher, the Bioethics Revolution, and Pharmaceutical Industry Funding of Academic Medical Science in Cold War America.

This paper examines anesthesiologist Henry K. Beecher's funding relationship with pharmaceutical manufacturer Edward Mallinckrodt, Jr. Beecher is a familiar figure to both medical ethicists and historians of medicine for his role in the bioethics revolution of the 1960s and 1970s. In particular, his 1966 article "Ethics and Clinical Research" is widely considered a turning point in the post-World War II debate about informed consent. We argue that Beecher's scientific interests should be understood in the context of his funding relationship with Mallinckrodt and that this relationship shaped the direction of his work in important ways. We also argue that Beecher's views on research ethics reflected his assumption that collaboration with industry was a normal part of how academic science is conducted. In the conclusion of the paper we suggest that Beecher's failure to consider his relationship with Mallinckrodt as worthy of ethical deliberation has important lessons for academic researchers who collaborate with industry today.

Repository Corticotropin Versus Glucocorticoid for Nephrotic Syndrome: When Will We See the Evidence?

Despite little evidence supporting its superiority to glucocorticoid therapy, use and expenditures for repository corticotropin (rACTH) injection (H.P. Acthar Gel; Mallinckrodt) have increased dramatically in the last 5 years, particularly among a small number of nephrologists, rheumatologists, and neurologists. Recently, the manufacturer justified the extremely high and rapidly increasing cost of rACTH by citing the ongoing need to generate clinical data to support its use. We test this assertion by investigating the quality and provenance of the evidence likely to emerge in the foreseeable future. We identified all completed, in-progress, and proposed studies of rACTH registered at ClinicalTrials.gov. 75 studies representing 2,953 participants met inclusion criteria. Studies addressed primarily nephrologic (n = 23), rheumatologic (n = 28), and neurologic (n =22) indications. Of the 23 studies proposed for renal indications (enrollment, 33 ± 49 [mean ± SD]), 11 were not randomized, 8 compared only different rACTH treatment regimens, and 4 compared rACTH to placebo. No studies of rACTH proposed for renal indications included an rACTH-free arm receiving active treatment (ie, another form of immunosuppression). We conclude that evidence emerging in the foreseeable future is unlikely to broadly support rACTH use over lower-cost glucocorticoid-based alternatives for renal indications.

Promoting opioids, a story about how to influence medical science and opinions.

Key origins of the opioid crisis in the US lie in some pharmaceutical companies' substantial efforts to sell prescription painkillers. To legitimize opioids, the companies built up a body of medical science and opinions, and channels with which to communicate. Archival searches found 876 contracts that together provide information on how Mallinckrodt, an opioid manufacturer, attempted the ghost-management of medicine. These records-available because of litigation-involved contract research organizations, medical education and communication companies, publishers, professional societies, researchers, and other people who could be Mallinckrodt's agents. Together, they produced and circulated scientific messages to increase physicians' comfort with prescribing opioids. This article gives an overview of that activity, as seen in the contracts and related documents.