Why Big Lies Matter: Lessons From the Bezwoda Affair

George W. Sledge, Jr, MD

Disclosures

Introduction

The facts of the case are straightforward. Werner Bezwoda is a South African clinical investigator who has in recent years presented 2 randomized trials comparing high-dose chemotherapy and autologous stem cell transplantation with standard-dose chemotherapy for patients with breast cancer. Both trials suggested a striking benefit of high-dose chemotherapy for both lymph node-positive and metastatic breast disease. One of these trials was considered sufficiently important to earn Dr. Bezwoda a plenary session lecture at the annual meeting of the American Society of Clinical Oncology. Because of the importance of these results, their striking positivity, and because of differences in the way in which transplant therapy was delivered, American investigators wished to examine Dr. Bezwoda's work before launching a confirmatory trial. Dr. Bezwoda's work was (after some delay) audited by a group of American physicians. The audit team discovered significant failings in Dr. Bezwoda's records, sufficient to raise the question of academic fraud. Dr. Bezwoda, in a letter, has admitted committing this fraud.[1]

I do not wish to discuss Dr. Bezwoda's reasons for committing scientific fraud. No one can read another's mind, let alone another's soul, and few of us have lived perfect lives. Scientific fraud occurs for all sorts of reasons, from the venal to the ideological. The sociology of scientific fraud is fascinating and the subject of several papers. That is not the subject of this editorial.

Actions have consequences, and Dr. Bezwoda's big lie has had and will continue to have several. Some of these, in the grand scheme things, are trivial: the time wasted by the ASCO audience, the sudden decline in Dr. Bezwoda's speaking engagements likely to ensue, and the time devoted to writing this editorial. But some of the consequences are important. And this is why big lies (and this was a very big lie) matter. Consider the following:

  • Big Lies Hurt Patients

    High-dose chemotherapy is considerably safer than it once was, but by no means is it nontoxic. The dynamics of doctor-patient interactions include the tendency by physicians to emphasize the most positive results. Dr. Bezwoda's data, in both the adjuvant and metastatic settings, were the most positive results available (some would argue the only positive results). It is reasonable to assume that some physicians made recommendations on the basis of Dr. Bezwoda's data (I certainly discussed these results with many of my patients). It is also reasonable to assume that some patients gave their informed consent on the basis of faulty information. And, it is reasonably likely that some patients suffered injury because of this faulty information. Primum non nocere: the first thing is to do no harm.

  • Big Lies Hurt Disciplines

    High-dose chemotherapy for breast cancer has been one of the hot-button issues in oncology for more than a decade. It is an issue that has by no means been decided, particularly in the high-risk adjuvant setting, where we have limited numbers of trials available and limited follow-up in those trials. Other trials are still accruing patients. It is still quite possible, Dr. Bezwoda's fraudulent claims notwithstanding, that high-dose chemotherapy for breast cancer may save lives.

    But the field of high-dose chemotherapy will be tarnished by Dr. Bezwoda's big lie. It is inescapable. Transplant physicians have made Dr. Bezwoda's data a centerpiece of their public presentations in recent years. Some have used it as a club to beat down skeptics. By doing so, transplanters unwittingly tied the reputation of their discipline in the breast cancer arena to his results. High-dose chemotherapy will be injured in Dr. Bezwoda's fall from grace (again, with regards to breast cancer; the procedure remains well-established for other indications). It will be difficult for a transplanter to discuss high-dose chemotherapy in breast cancer without audible snickers from the audience.

    Human nature being human nature, some will rejoice in this. As a nontransplanter, and transplant skeptic, I do not. The transplant researchers I know are honest scientists who only want what is best for their patients. They have conducted large, well-controlled, carefully monitored trials. And because Dr. Bezwoda's big lie will tarnish high-dose chemotherapy, it will become increasingly difficult to enroll patients in ongoing randomized trials that may actually give us an honest answer. High-dose chemotherapy trials are testing an important hypothesis in a scientifically rigorous fashion. Dr. Bezwoda's big lie doesn't just hurt the transplant field: it hurts us all.

  • Big Lies Hurt Institutions

    The University of Witwatersrand -- and South African scientists -- are not to blame for Dr. Bezwoda. By all accounts, they have responded promptly to the discovery of fraud and fully supported the investigation that led to its discovery. South African investigators have a long and honorable history of participation in clinical trials in oncology; the University of Pretoria, for instance, has been a long-standing and active member of the Eastern Cooperative Oncology Group. But South African investigators are likely to pay a price for Dr. Bezwoda's big lie, a perverse and undeserved guilt by association.

  • Big Lies Hurt Science

    The culture of science is based on trust. When a researcher presents his work in public, his data are taken at face value. One may interpret data in different ways, and one may question aspects of study design and statistical methodology. But one has to trust the basic data presented and those who present the data. If we cannot, the entire atmosphere of science is poisoned. Dr. Bezwoda's big lie has poisoned the atmosphere of science, and not just for scientists. The public relies on our truthfulness as investigators, particularly where the lives of citizens are directly at stake. Unethical and dishonest clinical experiments have long-standing and disastrous effects on ethical and honest clinical experiments, a Gresham's law of science. For example, African-American patients (and healthcare professionals, in my experience) still regularly raise the United States government's vile Tuskeegee syphilis experiments as a reason for not entering clinical trials. Never mind that these experiments are ancient and date from an era lacking basic safeguards, such as an Institutional Review Board. They still dog clinical research decades after their conclusion. We can only hope that Dr. Bezwoda's big lie will not have a similar effect.

    Where do we go from here? In coming weeks and months, investigators and practicing physicians will need to mull over the implications of l'affaire Bezwoda. Though only one study was audited, the discovery of fraud in that trial casts a shadow over all of the previous work by the investigator in question. This necessarily includes the metastatic breast cancer trial published in the Journal of Clinical Oncology by Dr. Bezwoda.[2] In the short term, however, patients considering high-dose chemotherapy should be notified that one of the great pillars in breast cancer's transplant temple was made of clay and has washed away.

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