Saturday, September 15, 2007

Most Science Studies Appear to Be Tainted By Sloppy Analysis (Wall Street Journal)

Interesting article by Robert Lee Holtz at the Wall Street Journal about mistakes in published research. He references the work of Dr. John Ioannidis, who studies research methods at the University of Ioannina School of Medicine in Greece and Tufts University. It also references an even more interesting paper he published in 2005.

From the article:

"Flawed findings, for the most part, stem not from fraud or formal misconduct, but from more mundane misbehavior: miscalculation, poor study design or self-serving data analysis. 'There is an increasing concern that in modern research, false findings may be the majority or even the vast majority of published research claims,' Dr. Ioannidis said. 'A new claim about a research finding is more likely to be false than true.'"

"The hotter the field of research the more likely its published findings should be viewed skeptically, he determined."

"Take the discovery that the risk of disease may vary between men and women, depending on their genes. Studies have prominently reported such sex differences for hypertension, schizophrenia and multiple sclerosis, as well as lung cancer and heart attacks. In research published last month in the Journal of the American Medical Association, Dr. Ioannidis and his colleagues analyzed 432 published research claims concerning gender and genes."

"'Overeager researchers often tinker too much with the statistical variables of their analysis to coax any meaningful insight from their data sets. People are messing around with the data to find anything that seems significant, to show they have found something that is new and unusual,' Dr. Ioannidis said."

From the paper:
The paper lays out several factors that influence the probability of the results of a study being true:

Corollary 1: The smaller the studies conducted in a scientific field, the less likely the research findings are to be true ... other factors being equal, research findings are more likely true in scientific fields that undertake large studies, such as randomized controlled trials in cardiology (several thousand subjects randomized) than in scientific fields with small studies, such as most research of molecular predictors (sample sizes 100-fold smaller).

Corollary 2: The smaller the effect sizes in a scientific field, the less likely the research findings are to be true ... research findings are more likely true in scientific fields with large effects, such as the impact of smoking on cancer or cardiovascular disease (relative risks 3–20), than in scientific fields where postulated effects are small, such as genetic risk factors for multigenetic diseases (relative risks 1.1–1.5). Modern epidemiology is increasingly obliged to target smaller effect sizes. Consequently, the proportion of true research findings is expected to decrease.

Corollary 3: The greater the number and the lesser the selection of tested relationships in a scientific field, the less likely the research findings are to be true ... research findings are more likely true in confirmatory designs, such as large phase III randomized controlled trials, or meta-analyses thereof, than in hypothesis-generating experiments.

Corollary 4: The greater the flexibility in designs, definitions, outcomes, and analytical modes in a scientific field, the less likely the research findings are to be true ... Adherence to common standards is likely to increase the proportion of true findings. The same applies to outcomes. True findings may be more common when outcomes are unequivocal and universally agreed (e.g., death) rather than when multifarious outcomes are devised (e.g., scales for schizophrenia outcomes). Similarly, fields that use commonly agreed, stereotyped analytical methods (e.g., Kaplan-Meier plots and the log-rank test) may yield a larger proportion of true findings than fields where analytical methods are still under experimentation (e.g., artificial intelligence methods) and only “best” results are reported.

Corollary 5: The greater the financial and other interests and prejudices in a scientific field, the less likely the research findings are to be true ... Prejudice may not necessarily have financial roots. Scientists in a given field may be prejudiced purely because of their belief in a scientific theory or commitment to their own findings. Many otherwise seemingly independent, university-based studies may be conducted for no other reason than to give physicians and researchers qualifications for promotion or tenure.

Corollary 6: The hotter a scientific field (with more scientific teams involved), the less likely the research findings are to be true ... With many teams working on the same field and with massive experimental data being produced, timing is of the essence in beating competition. Thus, each team may prioritize on pursuing and disseminating its most impressive “positive” results. “Negative” results may become attractive for dissemination only if some other team has found a “positive” association on the same question. In that case, it may be attractive to refute a claim made in some prestigious journal. The term Proteus phenomenon has been coined to describe this phenomenon of rapidly alternating extreme research claims and extremely opposite refutations. Empirical evidence suggests that this sequence of extreme opposites is very common in molecular genetics.