The Skeptical Professional's Guide to Rational Prescribing

The Impact of Scientific Fraud and Misconduct

Charles E. Dean

• Publisher: CRC Press
• Year: 2022
• ISBN:
  9781000572841
• Edition: 1
• Topic: Medicina
• Subtopic: Etica in medicina

The raging COVID-19 pandemic has shaken our trust in science. This volume reviews the evolution of misconduct and fraud in science, the many steps taken to alleviate the problem, and the likelihood that it will continue, given our profit-driven healthcare system. Contents are set in a clinical context, wherein misconduct and fraud affect rational prescribing, a process that depends on balancing the risk–benefit ratio of treatments, whether pharmacologic or psychotherapeutic. The clinical consequences can be significant, in that the efficacy of treatments can be vastly overplayed, adverse effects minimized, and costs to the healthcare system increased if corrective measures are not taken.

Key Features

• Discusses the various aspects of cheating in publications: spin, protocol changes; failure to publish negative studies, including current data on the publishing industry and its issues, like the menace of predatory journals, poor peer review, coupled with lack of early education in ethics, and its significant impact on rational prescribing.

• Assesses the impact of misconduct and fraud on clinicians and healthcare professionals as they attempt to balance the risk–benefit ratio which is supported by multiple contemporary studies.

• Presents shocking data on bribes to physicians, journal editors and other key opinion leaders, exposing the ultimate root of the problem which lies in the economics of the healthcare system, badly in need of repair.

1Regulations, the Growth of Pharma, and Diagnostic Expansion, 1951–2013A Wealth Trifecta

DOI: 10.1201/9781003267218-2

Introduction

In order to understand the context in which institutions and investigators have been enmeshed in a culture of misconduct, we must examine the development of the medical-industrial complex, a phenomenon that developed very slowly during the 18th and 19th centuries, but then accelerated in the 1950s. The early history of this transition has been described in detail by Paul Starr.¹ In the 18th century, physicians were held in little regard and had no organizational power. During the early 19th century, medicine in general lacked any significant claim to trust on the part of the public, leading families to provide much of the care for those who became ill. However, by the middle of the 19th century, science had provided evidence for the bacterial origin of tuberculosis, cholera, typhoid, and other infectious diseases, eventually leading to laboratory tests that could identify the organisms. In 1905, the spirochete responsible for syphilis was identified, while the Wasserman test for syphilis was introduced in 1906.^{1, p.137} This was a very significant development, given the number of cases in the asylums, and a significant boost for the reputation of physicians and their role as caregivers. However, the early psychiatrists, often labeled “alienists,” did not fare so well, given their isolation in the burgeoning system of asylums, and the often toxic and brutal therapies inflicted on the patients, including surgical removal of the uterus, teeth, and sections of the gut, extreme waterboarding, injections of horse serum and malarial parasites, cold showers, hyperthermia, restraints, and physical abuse.^2,3

Nevertheless, advances in science spurred a transition in medical care from the household to the market, or, as Starr put it, the conversion of health care into a commodity, a conversion that led to specialization of labor, more distancing between the ill and their caregivers, and a shift in the number of caregivers to men.^{1, p.22} By the mid-20th century, 26% of physicians were employed by institutions. Given the demands on their time and expertise, they began to develop more interest in research and teaching. At the same time, and somewhat paradoxically, physicians moved to enhance their status and financial interests by an anti-organizational stance. As the years passed, physicians railed against health insurance, health-maintenance organizations, and other forms of organized medicine but became enamored with the wealth of the pharmaceutical companies.

Indeed, a vast research structure had begun to develop as early as the 1930s, with the founding of the National Institutes of Health in 1930 and the National Cancer Institute in 1937.^{1, p.340} We must recognize as well the rise of the drug companies that occurred prior to the landmark regulations we will review shortly. From the 1940s to the 1950s, the 15 largest drug companies had 80% of the sales and 90% of the profits.⁴ In 1945, Pharma began to increase its investment in research, spending some $40 million, vs $25 million from foundations, universities, and other sources.^{1, p.339} By 1959, investment in research and development by Pharma reached $170 million,^{5, pp.68–69} but sales, profits, and investment in research would increase dramatically over the next several decades.

Regulations and legislative landmarks

In 1951, the U.S. Food and Drug Administration (FDA) decreed that new medications were to be available by prescription only.⁶ This was a seismic change from the previous centuries that were awash in homemade cures and potions available to anyone. No prescription was needed, despite the toxic ingredients, including mercury, cocaine, opium, and lithium. As Gerald Posner has noted,^{7, pp.6–9} these compounds, some 50,000 of them, were often labeled as “miracle cures,” with sales eventually reaching $100 million yearly.^{7, p.24} In addition, the many small manufacturers of these compounds competed with the burgeoning pharmaceutical industry of the 19th century, which included Squibb, Wyeth, Eli Lilly, and Burroughs Wellcome. These companies heavily invested in developing and promoting opiate-based pain remedies, and, in the case of Merck, promoting cocaine for a variety of ailments, including depression, asthma, and dental pain. At one point, cocaine was listed in the top five best-selling drugs. Similarly, in 2020, we find a resurgence of interest in opioids for treatment-resistant depression and psychedelics (psilocybin, mescaline, ketamine, 3,4 methylenedioxyamphetamine [MDMA] for an ever-expanding list of psychiatric disorders).⁸

The 1951 requirement by the FDA resulted in the transfer of additional power to physicians and Pharma, and the rapid development of psychotropic drugs. These included meprobamate (Equanil) in 1955, followed shortly by antipsychotics, antidepressants, and additional anxiolytics, notably chlordiazepoxide (Librium) in 1960 and diazepam (Valium) in 1963.² During the 1960s, chlordiazepoxide was the best-selling drug in the United States, a marker of the upward trend in industry wealth. In 1962, amendments to the Food, Drug, and Cosmetic Act mandated that new drugs were to be aimed at specific disease states, further stimulating growth of the medical-industrial complex, and the transition to a biologically oriented psychiatry.² The specificity of disease, however, was not a new idea. Indeed, Thomas Syndenham in the 17th century had advocated that we consider illnesses as specific entities.⁹ As I have shown, the search for the specificity of disease and treatment, based on the classic medical model, forced psychiatry into a position where it had to show progress in the area, despite the obstacles,^10,11 meaning more dependence on Pharma and its wealth.

The passage of the Bayh-Dole Act in 1980 was another benchmark, in that it gave universities and biotechnology companies the power to patent discoveries,¹² even if the research had been sponsored by the National Institutes of Health (NIH), which at that time was the primary provider of tax dollars for research. As Marcia Angell, the former editor of the New England Journal of Medicine (NEJM), has noted,¹² Bayh-Dole was a bonanza for Pharma, and fertilized the growing collaboration between academia and Pharma. Indeed, the editor of NEJM expressed his concern in 2004 over the advent of the medical-industrial complex,¹³ but this was 20 years after Bayh-Dole, far too late.

Yet another boost for Pharma and prescribers was the appearance of the 3rd edition of the Diagnostic and Statistical Manual of the American Psychiatric Association, the DSM-III,¹⁴ an enterprise that expanded the number of diagnosable mental disorders to 265. Only 7 years earlier, the Feighner research criteria¹⁵ had stressed that the scientific literature permitted the diagnosis of only 16 disorders, while the DSM-I of 1952,¹⁶ had specified 106. The DSM-III acknowledged that most disorders had no valid information on their course, treatment, or pathophysiology. Despite misgivings over the epidemic of mental disorders,^17,18 subsequent editions continued to expand the numbers of diagnoses, reaching some 350 in the DSM-5 of 2013.¹⁹

While the DSM-III was the subject of multiple critiques^20,21 regarding its consensus-based approach and the use of diagnostic checklists (operationalized criteria), the advent of 265 sanctioned diagnoses gave psychiatrists an unprecedented opportunity to increase their prescriptions for psychotropic drugs. As a corollary, DSM-III also provided Pharma an opportunity to increase its neurobiological research into a host of relatively new disorders—fertile ground indeed, since most had no valid information on their course, treatment, or pathophysiology.¹⁴ Nor was there any evidence of an objective, independent biomarker that could validate a diagnosis, a statement true in 2021, despite 60 years of increasingly complex neurobiological research.^22,23

In 1984, Congress provided Pharma with another bonanza by passing the Drug Competition and Patent Restoration Act (Hatch-Waxman) that added another 5 years of patent protection,¹² and even more time if regulatory delay had stymied marketing. This resulted in another 20 years of patent protection for new drugs, a huge boost for profits. As Mike Magee has noted in his new book,...