A recent study in the Journal of Medical Ethics found that 788 research papers published in medical journals between 2000 and 2010 were retracted for serious errors or falsified data.^1,2 Study author Grant Steen, PhD, told The ASCO Post that U.S. scientists were responsible for 169 of the papers retracted for inadvertent yet serious errors, as well as 84 papers retracted for blatant fraud. "In any case, during the sample period I used for the study, nearly 5 million papers were published, so the short version of what I found is that relatively few scientific papers are retracted," said Dr. Steen.

Yet, Dr. Steen noted an interesting, if not alarming pattern. "Among the papers retracted for error, only about 18% of authors had a previous retraction. However, among papers retracted for out-and-out fraud, more than half of those authors had previous retractions," said Dr. Steen.

According to Dr. Steen, this finding can be interpreted in two ways. Authors of a fraudulent paper are likely to have all their papers retracted, whether or not fraud or error was committed in each publication. "But the other explanation, which I tend to favor, is that people who engage in fraud have a pattern of abusing the literature," said Dr. Steen.

While it is impossible to look into the mind or motive of another, there are some things we can discern from patterns that emerge in studies such as Dr. Steen's. Since falsified papers were more likely to appear in high-profile medical journals as opposed to less prestigious publications, we can intuit that the "publish or perish" ethos might be a factor behind this behavior. "We need to be cautious; some clinical researchers perceive a paper published in a journal with a high impact factor as an open door to an upward career move, and they are willing to falsify data to walk through that door," said Dr. Steen.

Breaches of Trust

Trust is the cornerstone of science and medicine, especially in the oncology setting where the specter of mortality is a constant companion. We have seen breaches in this fundamental compact; the infamous Tuskegee syphilis experiment is still cited as a reason for the reluctance of many African-Americans to enter clinical trials. The creation of the 1979 Belmont Report, which defines the basic ethical guidelines for the conduct of clinical trials, was created as a result of the Tuskegee episode.

Guidelines are imperative, but they do not prevent data falsification in clinical research. Decades after Tuskegee, South African clinical investigator Werner Bezwoda fabricated data in two randomized breast cancer trials. Bezwoda's scientific deception and its lamentable consequences have been widely discussed in the literature.

Did Bezwoda Make Us More Honest?

The ASCO Post recently asked ASCO President George W. Sledge, MD, if the Bezwoda affair was a wakeup call, making data falsification less likely. "I don't think so, but that's not a negative judgment. The culture of scientific study is based on assumed honesty. We don't have the inclination or time to critically analyze the raw data underlying the published work. When I open an issue of JCO, my starting notion is that the content between the covers is honest reporting."

However, Dr. Sledge mentioned that most authors of scientific papers have an agenda, a bias, and to a certain extent they are going to generate data that will support their underlying hypothesis. "But if we cannot rely on the basic assumption of honest scientific reporting, then the whole system crumbles," said Dr. Sledge. He stressed that distrust of scientific reporting stems from a small minority of investigators. "During my 30-year career, I can point to maybe a half dozen cases of data falsification in the oncology literature," said Dr. Sledge.

Built-in Checks

Dr. Sledge explained that concern over fraud in clinical research is justified; however, we have built-in checks protecting the system on multiple levels. "For instance, a positive result from a local institutional study will produce a host of investigators wanting to repeat those results. If identical trials using the same agent or combination are negative, people won't necessarily assume fraud, but they will discount the data," said Dr. Sledge.

Dr. Sledge noted that Bezwoda claimed to have done a phase III trial in a single institution. "None of us knew anything about how things were done in Johannesburg, South Africa. But most of what we gain on a clinical level in oncology is from multicenter cooperative group phase III trials, and with their manifold levels of checks it is impossible to skew the data," said Dr. Sledge.

A Few Bad Apples

In 2000, Dr. Sledge responded to the Bezwoda debacle in an editorial discussing the consequences that lies have on patients, disciplines, institutions, and science. Even though clinical research mischief is incredibly rare, Dr. Sledge acknowledged that breaches of ethical behavior such as Tuskegee and Bezwoda can "dog clinical research decades after their conclusion."

Asked if we need more emphasis on ethics in medical school, Dr. Sledge responded, "The ethics of caring for sick patients in the clinic are on a different level than those of writing a scientific paper, so I'm not sure teaching a general ethics course to freshmen medical students will make a whole lot of difference."

"However," continued Dr. Sledge, "Discussions of scientific integrity should be a part of every researcher's educational process, and certainly in the clinic as well as the lab. But this is more of a postgraduate than a medical school fundamental, since that is where people learn how to do research."

As Dr. Sledge pointed out, we can interpret data in different ways, we can question trial design and methodology, but, in spite of a few bad apples, "we must trust the honesty of the data and the investigator at face value. If not, the whole system and everyone in it is in jeopardy."

Dr. Steen said that his study emphasized the need to back trust up with a healthy dose of scientific skepticism prior to publication. "If something seems too good to be true-as was the case with Bezwoda-then it is incumbent on the scientific community to replicate and verify," concluded Dr. Steen. ■

References

1. Steen RG: Retractions in the scientific literature: Do authors deliberately commit research fraud? J Med Ethics 37(2):113-117, 2011.

2. Steen RG: Retractions in the scientific literature: Is the incidence of research fraud increasing? J Med Ethics December 24, 2010 (epub ahead of print)