Responsible Conduct of Research

Abstract

Responsible conduct in research has gained increased importance with the recent increase in research activity. This chapter aims to highlight the following several facets of research misconduct: (1) defining what constitutes research misbehaviors; (2) the differences in the prevalence of misbehaviors in various regions of the world; (3) the reasons that lead investigators to commit research misconduct; and (4) the type of measures that can be instituted to enhance the responsible conduct in research. In regards to the latter, a recommendation will be made for developing training programs that focus on preventing research misconduct.

Three Notorious Cases

Case 1: Jon Sudbö’s Work on Oral Cancer Chemo-Prevention

In 2005, Jon Sudbö and his colleagues published a paper in the Lancet titled “Non-steroidal anti-inflammatory drugs and the risk of oral cancer: a nested case-control study”. In that paper, Sudbö and his team found a protective effect of non-steroidal anti-inflammatory drugs (NSAIDs) against oral cancer. Skepticism of fabrication of Sudbö’s data was soon raised when it was found that the cancer patient database (the core base for Sudbö’s study) was never used. An investigation revealed that Sudbö had fabricated data of more than 900 subjects in his study. The paper was very soon retracted from the Lancet (Pincock 2006). Should this paper not have been promptly retracted, NSAIDs would have become accepted as a recommended chemo-protective agent against oral cancer that might have resulted in providing false assurances to heavy smokers who might have quite smoking otherwise and also the design of futile clinical trials to provide prospective evidence of a chemo-protective effect. The Lancet’s prompt retraction aborted those potential consequences.

Case 2: Naoyuki Nakao and the COOPERATE Study

In 2003, a team of researchers led by Naoyuki Nakao published their clinical trial, named the COOPERATE trial, in the Lancet. The paper showed that when a dual-drug therapy consisting of angiotensin-II receptor blocker (losartan) and angiotensin converting enzyme inhibitor (trandolapril) is given to patients, renal disease was delayed compared with single-drug therapy. Consequently, many clinicians modified the treatment protocols for their hypertensive patients and started to prescribe the dual-drug therapy. However, in 2006, concerns surfaced over the validity of the COOPERATE trial (e.g., claims regarding a reduction in protein loss by the kidneys using the dual therapy was viewed as being unrealistic (Bidani 2006) and skepticism arose over the integrity of the methodology and data management as a whole).

Following repeated concerns, the Lancet made a request to undertake an investigation into the integrity of the COOPERATE trial. The results of the investigation concluded that the study had been fabricated. Consequently, the Lancet retracted the paper in 2009 due to several ethical breathes (“Retraction. Combination treatment of angiotensin-II receptor blocker and angiotensin-converting-enzyme inhibitor in non-diabetic renal disease (COOPERATE): a randomised controlled trial” 2009). However, by that time, an estimated 140,000 patients in the US alone were receiving this combination instead of the traditional mono-therapy, and over a considerable amount of time. The length of time between publication and retraction had exposed a large number of patients to a scientifically foundationless therapy.

Case 3: Andrew Wakefield and the MMR Vaccine

In 1998, Andrew Wakefield and his colleagues reported a case series of 12 children with reactive intestinal changes and pervasive developmental disorder (mostly autism) that followed MMR vaccination. Those findings created a worldwide scare from what the authors called in their paper the “MMR syndrome (Wakefield et al. 1998). The years following Wakefield’s publication witnessed greater reluctance by parents to using vaccines for their children that lead to outbreaks in measles and mumps in various countries (McBrien 2003; Pugh 2002), and recently in the USA (Centers for Disease Control and Prevention n.d.). These outbreaks were seen in non-immunized children, and in some cases were linked with parental attitude towards children’s vaccination. Other studies investigating the link between MMR vaccine and autism failed to prove Wakefield’s findings. In 2010, following intensive investigations, the results of the 1998 paper were found to have been falsified with substantial tampering of children’s histories (Deer 2011).The Lancet eventually retracted the paper in 2010 based on ethical violations related to children’s recruitment process and the reviews by the research ethics committee (“Retraction – Ileal-lymphoid-nodular hyperplasia, non-specific colitis, and pervasive developmental disorder in children” 2010). Further ethical violations were also revealed when Wakefield had a financial conflict of interest and did not disclose it to his colleagues nor to the journal. Wakefield, whose name has been erased from the General Medical Council Register, continues to deny any wrongdoing and insists on the association he had found between MMR vaccine and autism (Ziv 2015).