An article by Naveed Saleh, MD, MS, for MDLinx | January 2020 with Edits by JP Saleeby, MD
Between 2001 and 2010, the number of studies published per year increased by 44%. But not all these articles passed muster. Many that were published in prestigious peer-reviewed journals were retracted or redacted. Indeed, during this same 10-year period, the number of annual retractions exploded by 1,000%, according to some estimates.
Similar research suggests that the number of retracted publications ballooned by 11.06 times during this interval. Since Evidence Based Medicine (EBM) is almost completely reliant on what is published in the medical literature, this poses quite a dilemma. Now researchers, physicians and practitioners on the front lines will have to questions what is written in the journals. This will cause doubt and confusion and water-down clinical guidelines.
Retracted papers are no joke. Issues that contribute to retraction include:
- duplicate publication
- authorship issues
- ethical issues
- statistical manipulations
- funding bias
Significant consequences and fallout:
Retractions do not just injure academic reputations and mar the credibility of high-powered peer-review journals, they can have far-reaching repercussions in the public and on individual patients.
The damage that crank studies do to the public is great in both financial and human terms. Although retracted studies account for less than 1% of NIH funding, they represent more than $58-million of NIH losses during a period of 20-years.
Consider the conclusion of a systematic survey assessing retractions in oncology, published in Research Integrity and Peer Review. “The number of retracted publications in the cancer literature is increasing rapidly, and cancer retractions are largely due to academic misconduct as opposed to honest error,” wrote the authors.
“Consequences to cancer patients and the cancer research community at large can be significant as invalid publication may have a detrimental effect on patients treated in everyday practice. Despite the implications of this important issue, cancer journals fall short of the well-articulated COPE/ICMJE guidelines on the reporting of retractions.”
Let us take a brief look at five notable studies that have been retracted. These articles were among the 10 most highly cited retracted papers, according to Retraction Watch. (The list was current as of May 2019.)
Incredibly, many of these articles continued to be cited even after they were retracted:
Primary Prevention of Cardiovascular Disease with a Mediterranean Diet
Publication: The New England Journal of Medicine
Authors: Estruch R, et al.
Year published/retracted: 2013/2018
Number of citations (pre-retraction/post-retraction): 2266 (1895/371)
In this high-powered randomized trial out of Spain, the authors found that adherence to a Mediterranean diet replete with extra-virgin olive oil or nuts decreased the frequency of severe cardiovascular events in participants at high risk for cardiovascular disease.
The authors later retracted the article “because of irregularities in the randomization procedures.”
Editors at NEJM wrote: “An analysis of reports of randomized trials for improbable distributions of baseline data included 934 reports published in the Journal and identified 11 with distributions of baseline variables that did not appear consistent with randomization.”
Visfatin: A Protein Secreted by Visceral Fat That Mimics the Effects of Insulin
Authors: Fukuhara A, et al.
Year published/retracted: 2005/2007
Number of citations (pre-retraction/post-retraction): 1324 (228/1096)
In this preclinical study, the authors found that fat tissue secretes proteins that exert insulin-like effects. “Further study of visfatin’s physiological role may lead to new insights into glucose homeostasis and/or new therapies for metabolic disorders such as diabetes,” they wrote.
Shortly after publication, valid concerns were raised about the insulin-mimetic actions of visfatin. Furthermore, other research showed that visfatin was the same as a previously discovered growth factor called pre-B cell colony-enhancing factor (PBEF). Consequently, retraction was a no-brainer.
Cardiac Stem Cells in Patients with Ischaemic Cardiomyopathy (SCIPIO): Initial results of a randomised phase 1 trial
Publication: The Lancet
Authors: Bolli R, et al.
Year published/retracted: 2011/2019
Number of citations (pre-retraction/post-retraction): 926 (904/24)
In this phase 1 trial, investigators found that the infusion of cardiac stem cells into coronary arteries ameliorated systolic function in the left ventricle and shrunk infarcts in those with heart failure secondary to heart attack.
In their retraction, editors at The Lancet raised concerns about the laboratory work done by the principal investigator, Piero Anversa of Harvard University, but cleared lead author, Roberto Bolli, of any conscious wrongdoing.
Spontaneous Human Adult Stem Cell Transformation
Publication: Cancer Research
Authors: Rubio D, et al.
Year published/retracted: 2005/2010
Number of citations (pre-retraction/post-retraction): 755 (326/429)
This Spanish study was purported to be the first to demonstrate that human adult stem cells could undergo spontaneous transformation, thus pointing to an origin of cancer stem cells. The authors claimed that this finding suggested the therapeutic potential of mesenchymal stem cells.
In the retraction, Cancer Research editors noted: “Upon review of the data published in this article, the authors have been unable to reproduce some of the reported spontaneous transformation events and suspect the phenomenon is due to a cross-contamination artifact. Five of the seven authors have agreed to the retraction of this paper.”
Combination Treatment of Angiotensin-II Receptor Blocker and Angiotensin-converting-enzyme Inhibitor in Non-diabetic Renal Disease (COOPERATE): a randomised controlled trial
Publication: The Lancet
Authors: Nakao N, et al.
Year published/retracted: 2003/2009
Number of citations (pre-retraction/post-retraction): 731 (583/148)
In this study, Japanese researchers found that combining angiotensin-II receptor blockers (ARBs) and angiotensin-converting enzyme inhibitors (ACE inhibitors) in patients with non-diabetic kidney disease outperformed monotherapy.
Instead of providing evidence-based guidance, this study turned out to be an exercise in Murphy’s Law—anything that could go wrong did.
Take a look at the damage surveyed by the editors at The Lancet:
“[An investigation committee] concluded that contrary to statements in the paper, the trial had not been approved by the ethics committee of Gen Gen-Do Kimitsu Hospital. Also, contrary to the statement on patients’ consent, Dr. Nakao reposted that he had received verbal consent from patients shortly after the start of the study and written consent only during the study.
The involvement of a statistician could not be verified. The committee concluded that the trial was not a double-blind study, because Dr. Nakao knew the treatment allocation. In the attempt to assess the validity of the data, a sample of medical records was compared with the data provided by Dr. Nakao. The committee concluded that it was unable to prove the authenticity of the data,” they wrote.
Although researchers responsible for retracted studies evoke little sympathy from the scientific community, retractions or redactions often destroy careers. For researchers, retraction can be the kiss of death, with censure by the Office of Research Integrity a consequence. Furthermore, for those researchers who cross the line, publication output decreases by a median of 91.8% and funding dries up. This should be a warning to those who have published unethical or intentionally biased papers. It is unfortunate for the well-meaning researcher whose work is just not accurate. The consequences and collateral damage can be immense, so the push for ‘’truth’’ in publications must be a core-value upheld to the highest degree.