Carlos R. Hojaij: Ethics for psychiatrists*

 

On display in the relationship between doctors and drug companies are the grandeur and weakness of the medical profession and its noble aspirations and its continuing inability to fulfill them (Blumenthal, 2004).

The human malice has no limits when does not cause remorse, when acts loose memory as soon they exist (Kohn, 2003).

The normal reaction to this situation would be indignation, but indignation would be very risky, not a danger to life or being injured, but surely a threat to a career (Arendt, 1977).

 

            The withdrawal of Vioxx (rofecoxib) from the market in 2005 because of increased risk of stroke and myocardial infarction brought an opportunity to open a public discussion on medical ethics, the relationship between physicians and pharmaceutical industry. The drug had been on the market since 1999, used by about 84 million people world-wide, and was used in 2005 by an estimated 2 million people. In 2004, Vioxx reached $2.5 billion in sales. Its withdrawal represented the largest ever of a prescription drug (Topol, 2004).

            In 2004, Topol (2004) brought attention to following facts related to rofecoxib’s  launching process and related trials: 1. On May 21, 1999, Merck was granted United States Food and Drug Administration (US FDA) approval to market Vioxx; 2. the pivotal trial used for rofecoxib’s FDA approval included 8,076 patients with rheumatoid arthritis showed lower gastrointestinal toxicity than naproxen; 3. the findings of the of the pivotal trial was submitted only a year after, in 2000, to a peer reviewed journal with the results appearing in press on November 23, 2000; two years after the approval of the drug for sale, the FDA Arthritis Advisory Committee discussed concerns about the potential cardiovascular risks associated with rofecoxib; 5. on May 22, 2001, Merck, in a press release, reconfirmed Vioxx’s cardiovascular safety; 6. the press release was complemented by numerous papers in peer-reviewed journals written by Merck employees and their consultants; 7. “only by happenstance” in a trial involving 2,600 patients with colon polyps, in which patients with known cardiovascular disease were not included, was it discovered that 3.5% of the patients assigned to rofecoxib suffered myocardial infarction or stroke, compared with 1.9% of the patients assigned to placebo. The trial was stopped and treatment with rofecoxib discontinued. .

            In 2004, Topol and Falk (2004) brought to attention that during the five-and-a-half-year saga, several many epidemiological studies confirmed and amplified the concern about the risk of myocardial infarction and serious cardiovascular events with rofecoxib. Furthermore, FitzGerald, in 2004, reported suppression of the formation of prostaglandin I2 by rofecoxib in healthy volunteers. He also indicated that depression of postaglandin I2 formation may result elevation of blood pressure, acceleration of atherogenesis and predisposition to an exaggerated thrombotic response to rupture of an atherosclerotic plaque.

            Considering Topol’s seven points, it was felt then that time had come for an extensive and thorough investigation of responsibilities. Taking into account the number of patients and doctors involved in clinical trials for a drug such as rofecoxib, it was thought that only an investigation conducted by an international independent panel could produce effective results.

            The story of Vioxx prompted me in 2005 to write an editorial in the World Journal of Biological Psychiatry. I considered it beyond the scope of an editorial to discuss all the implications and consequences of a case like that of Vioxx, but I thought that at least one major issue should be addressed: that in a world moved by powerful economic interests, morality may decrease as financial profit increases and the collapse of morality promotes a permanent dullness in the human capability to react with indignation and revolt. In the same way as morals and ethics have been a part of everyday life, in the same way as the notions of right and wrong have been a natural part of every human being, in the same way as the respect for a law was a spontaneous attitude for the law being an intuitive expression of human behavior, people are now getting used to respond with complacence (if so) to the numerous assaults on their freedom and health. Even worse than that is the conviction that we all should respect and become submissive to any great power. Consequently, there is no acceptable space for discordance and divergence, the main characteristics of humans which permit freedom and promote evolution. It is expected that we all should give the same syntonic response, despite how bad this might be. In a world of only one voice, there is no voice at all. Historically, science started when man started to inquire about the nature of things, putting into doubt the previous certainty provided by religious faith. Progress in science has been always based on curiosity and an endless quest for improvement of life. However, if pragmatic science is not illuminated by philosophical principles and guided by universal values, it inevitably runs into the shadows of amorality: anything becomes permitted.

            Psychiatrists involved (or not) in research have to be aware of all aspects related to pharmacological practice: those directed at the patient, reflected in medicine and in the profession as a whole. Psychiatrists should constantly be aware of the dangerous power they have as prescribers, a power that should bring benefit to the patient, but can have drastic consequences. Psychiatrists who impart knowledge through lectures should always be free of any prejudice which could color their talk with a hidden and perverted message. Psychiatrists who are authors should be free of influences which could provoke distortions in order to achieve desirable financial results. The world we live in is chiefly motivated by financial interests which cover up all other values of civilization, a world that moves at a speed that many times transcends a regular capacity for control. It is a wheel turning around and provoking dizziness and a loss of clarity of consciousness. Time has come to slow down the financial adventure of looking for the cure for all the illnesses of the world, so that we can accept nature’s time scales, preserve the life that we have and respect for our patients, respect for medicine and doctors, and respect for researchers and companies that truly are making efforts to achieve progress in medical care.

            At the time the editorial on which this posting is based was written, the Chair of the Ethics Committee of the World Federation of Societies in Biological Psychiatry (WFSBP,)  Professor Hanfried Helmchen, posted on WFSBP’s website  a “proposal of recommendations” concerning “Ethical Implications of Relationships between Psychiatrists and the Pharmaceutical Industry.” As Professor Helmchen said, “the growing size and intensity of relationships between medicine and industry, as well as an increasing frequency of reports of questionable, incorrect or even unacceptable behavior of both individuals and institutions call for norms to regulate behavior and for measures to enforce these norms. In reality ...the aim is to safeguard the integrity of physicians as well as the industry and to avoid endangering the relationship between the physician and the patient.”

            Professor Helmchen’s proposal constituted a comprehensive and extensive document concerning this hot topic. It called attention to the core question in the doctors/industry relationship: “to what extent and by what means does industry exert influence on the patient/physician relationship” and “what are the effects of such possible influence with regard to (1) the gain of scientifically valid new knowledge, (2) the physician’s clinical judgment, (3) the medical education and distribution of medical knowledge, (4) the process and quality of care and (5) the perception of physicians by patients, colleagues and the general public with regard to their trust in both the individual physician and in medicine as a whole?” The document was well developed, based on bibliographic references, deeply reflective and lead to a series of 25 recommendations.

In addition, to ameliorate the chaotic situation at the time, I recommended in my editorial that the WFSBP obligates the organizers of its congresses to have all speaker participants officially disclose eventual conflict(s) of interest and to publish this list in the final program of the relevant Congress. I also recommended that all authors publishing in The World Journal of Biological Psychiatry submit a statement on conflict of interest. Furthermore, WFSBP’s Educational, Scientific and Research Committees were requested to make use of the proposed recommendations to develop formal recommendations to members involved in research and teaching.

References:

Arendt H. Eichmann in Jerusalem: A report on the banality of evil. Middlesex: Penguin Books; 1977.

Blumenthal D. Doctors and drug companies. New Engl J Med 2004; 351:1885 - 90.

FitzGerald GA. Coxibs and Cardiovascular Disease. New Engl J Med 2004; 351:1709 - 11.

Kohn J. Introduction. In Arendt H. Responsibility and judgment (Jerome Kohn editor). USA: Shocken Books: 2003.

Topol E. Failing the public health. rofecoxib, Merck, and the FDA. New Engl J Med 2004; 351:1707 - 1709.

Topol EJ, Falk GW. A coxib a day won’t keep the doctor away. Lancet 2004; 364 – 9.

 

Carlos R. Hojaij

January 5, 2017

 

*Based on an editorial published in The World Journal of Biological Psychiatry (2005; 6: 66-8).