Leemon McHenry

In this case study from litigation, we show how ghostwriting of clinical trial results can contribute to the manipulation of data to favor the study medication. Study 329 for paroxetine pediatric use was negative for efficacy and positive for harm. Yet the ghostwritten publication from this study concluded that paroxetine provided evidence of efficacy and safety and continues to be influential. Despite the role of named authors in revisions of the manuscript, the sponsor company remained in control of the message.

Traditionally, the three-pronged mission of our colleges and universities has been to provide high-quality education, encourage cutting-edge research, and promote professional and community service. The substitution of business-based policies for sound academic principles, however, has institutionalized a form of professional inequality that threatens all three. The growing distinction between tenured and tenure-track faculty members on the one hand and tenure-ineligible lecturers or part-time adjuncts on the other has produced an academic caste system that is undermining the raison d’être of our institutions of higher learning. This system is capricious, discriminatory, and unjust.

This paper is a deconstruction of a ghostwritten report of a randomized, double-blind, placebo-controlled efficacy and safety trial of citalopram in depressed children and adolescents conducted in the United States. Court documents revealed that protocol-specified outcome measures showed no statistically significant difference between citalopram and placebo. However, the published article concluded that citalopram was safe and significantly more efficacious than placebo for children and adolescents, with possible adverse effects on patient safety.

In this paper, I examine some of the most important theories of modern physics that support the notion that events are the basic ontological units of reality. The two main themes of this paper include: (1) physical evidence in support of an ontology of events, and (2) the increasing unification of physical theory until we arrive at the current state of two highly successful theories that are presently disunified within the search for a comprehensive, unified theory. With the revolutionary developments in physics at the end of the nineteenth century, the mechanistic materialism of Newtonian physics began to break down and the ancient trinity of space, time and matter has been gradually replaced by the notion of the energy field. Physicists and philosophers who have held an event ontology specifically for its compatibility with electromagnetism, relativity theory and quantum mechanics include: Albert Einstein, Alfred North Whitehead, Bertrand Russell, C. D. Broad, W. V. Quine, John Bell, Henry Stapp, and Milič Čapek among many others. For these theorists, events are the most fundamental entities of physical reality in contrast to the Aristotelian tradition which contends that events are secondary or dependent on physical substance.

The lingering controversy concerning the usefulness and safety of antidepressants for children and adolescents is likely to confuse clinicians. Recent papers perpetuate the claim that antidepressants are shown to be safe and effective in randomised controlled trials. Others claim that antidepressants have been shown to prevent suicides. In this editorial we address the manipulation of outcomes that result from academics’ alliance with industry. We explain how industry and key opinion leaders have distorted the clinician’s perception of the safety and usefulness of antidepressants for the treatment of depression in children and adolescents through publication bias, poor methodology, and selective reporting.

Scientific and ethical misconduct has increased at an alarming rate as a result of the privatization of knowledge. What began as an effort to stimulate entrepreneurship and increase discovery in biomedical research by strengthening the ties between industry and academics has led to an erosion of confidence in the reporting of research results. Inherent tensions between profit-directed inquiry and knowledge-directed inquiry are instantiated in psychopharmacology, especially in the co-option of academic activity to corporate objectives. The effects of these tensions are visible in research agendas, publication practices, postgraduate education, academic-industry partnerships and product promotion.

Corporate interests corrupt clinical trials, physicians and universities, undermining the foundation of evidence-based medicine. Philosopher Leemon McHenry and psychiatrist Jon Jureidini argue that the principles underlying Popper’s philosophy of science can protect clinical research from corporate malfeasance in a capitalist economy. Evidence-based medicine was a paradigm shift that is often praised as one of the greatest achievements of medicine in the twentieth century. This radical change in medical practice is based on epistemological hierarchies of evidence, from opinions of respected authorities, mechanistic reasoning and reports of expert committees at the bottom to various levels of observational studies and finally to randomized, placebo-controlled clinical trials at the apex. Randomized, placebo-controlled clinical trials, recognized as the gold standard of clinical experimentation, generally maintain their position in the hierarchies because when well-designed and well-conducted, they provide a basis for assessing harms and benefits, and help deter extravagant claims of efficacy and safety.

The goal of this paper is to expose the research misconduct of pharmaceutical industry-sponsored clinical trials via three short case studies of corrupted psychiatric trials that were conducted in the United States. We discuss the common elements that enable the misrepresentation of clinical trial results including ghostwriting for medical journals, the role of key opinion leaders as co-conspirators with the pharmaceutical industry and the complicity of top medical journals in failing to uphold standards of science and peer review. We conclude that the corruption of industry-sponsored clinical trials is one of the major obstacles facing evidence-based medicine.

Biomedical ethics requires that clinical trial participants be accurately informed of the potential risks associated with investigational medical products. We found that the vaccine manufacturer Merck made false statements to the trial participants about the safety of Gardasil in its Future II HPV vaccine trial in Denmark. The clinical study protocol specified that safety testing was one of the trial’s primary objectives, but the recruitment brochure given to trial participants stated this was not the case, as allegedly the vaccine had already been proven safe in previous trials. The advertising material for the trial and the informed consent forms stated that the comparator was saline or an inactive substance, when, in fact, it contained Merck’s proprietary aluminum adjuvant which is highly immunogenic. Several trial participants experienced long-term disabling symptoms during the trial, also some randomized to the adjuvant “placebo” control group. In all cases, their serious adverse events were dismissed as unrelated to the study treatment by Merck’s clinical investigators. We demonstrate that Merck’s published statements about the safety of their proprietary aluminum adjuvant is contradicted by the research evidence. The use of adjuvants as “placebos” in vaccine clinical trials is unethical as it makes it difficult to discover serious vaccine harms.