Persistence of Contradicted Claims in the Literature
Athina Tatsioni, MD; Nikolaos G. Bonitsis, MD; John P. A. Ioannidis, MD
JAMA. 2007;298(21):2517-2526.
Context Some research findings based on observational epidemiology are contradicted by randomized trials, but may nevertheless still be supported in some scientific circles.
Objectives To evaluate the change over time in the content of citations for 2 highly cited epidemiological studies that proposed major cardiovascular benefits associated with vitamin E in 1993; and to understand how these benefits continued being defended in the literature, despite strong contradicting evidence from large randomized clinical trials (RCTs). To examine the generalizability of these findings, we also examined the extent of persistence of supporting citations for the highly cited and contradicted protective effects of beta-carotene on cancer and of estrogen on Alzheimer disease.
Data Sources For vitamin E, we sampled articles published in 1997, 2001, and 2005 (before, early, and late after publication of refuting evidence) that referenced the highly cited epidemiological studies and separately sampled articles published in 2005 and referencing the major contradicting RCT (HOPE trial). We also sampled articles published in 2006 that referenced highly cited articles proposing benefits associated with beta-carotene for cancer (published in 1981 and contradicted long ago by RCTs in 1994-1996) and estrogen for Alzheimer disease (published in 1996 and contradicted recently by RCTs in 2004).
Data Extraction The stance of the citing articles was rated as favorable, equivocal, and unfavorable to the intervention. We also recorded the range of counterarguments raised to defend effectiveness against contradicting evidence.
Results For the 2 vitamin E epidemiological studies, even in 2005, 50% of citing articles remained favorable. A favorable stance was independently less likely in more recent articles, specifically in articles that also cited the HOPE trial (odds ratio for 2001, 0.05 [95% confidence interval, 0.01-0.19; P < .001] and the odds ratio for 2005, 0.06 [95% confidence interval, 0.02-0.24; P < .001], as compared with 1997), and in general/internal medicine vs specialty journals. Among articles citing the HOPE trial in 2005, 41.4% were unfavorable. In 2006, 62.5% of articles referencing the highly cited article that had proposed beta-carotene and 61.7% of those referencing the highly cited article on estrogen effectiveness were still favorable; 100% and 96%, respectively, of the citations appeared in specialty journals; and citations were significantly less favorable (P = .001 and P = .009, respectively) when the major contradicting trials were also mentioned. Counterarguments defending vitamin E or estrogen included diverse selection and information biases and genuine differences across studies in participants, interventions, cointerventions, and outcomes. Favorable citations to beta-carotene, long after evidence contradicted its effectiveness, did not consider the contradicting evidence.
Conclusion Claims from highly cited observational studies persist and continue to be supported in the medical literature despite strong contradictory evidence from randomized trials.
Showing posts with label Observational Studies. Show all posts
Showing posts with label Observational Studies. Show all posts
Thursday, December 6, 2007
Wednesday, September 5, 2007
Consent bias may reduce value of observational research
Consent bias may reduce value of observational research
By Liam Davenport
05 September 2007
Heart 2007; 93: 1116-1120
MedWire News: Consent bias may impact on observational research into ischemic heart disease, with clinically important prognostic variables associated with consent preferences, say Irish researchers.
Patients' right to privacy and confidentiality has been increasingly acknowledged in recent years. Although the implications of prior written consent have been discussed in terms of healthcare professionals, public attitudes have not been widely examined, and what research has been conducted has yielded mixed results.
Researchers have expressed concerns over the potential constraints of strict consent rules on observational research, so Brian Buckley, from the National University of Ireland in Galway, and colleagues sought to determine differences between adults who consent to participating in such research and those who do not.
They examined data on a representative cohort of 1609 patients with ischemic heart disease from 35 randomized general practices identified in 2001. Baseline questionnaires were sent to 1269 participants, with follow-up medical charts up to the years 2005-2006 located for 1592 patients.
In all, 876 (69%) of the questionnaires were returned completed. Of these, 574 (65.5%) gave consent for their participation in further research, the team reports in the journal Heart.
Multiple logistic regression analysis revealed that patients were more likely to consent to participation in further research if the factors they had undergone prior percutaneous transluminal coronary angioplasty, a last recorded blood pressure of less than 140/90 mmHg, a last recorded total cholesterol level of less than 5 mmol/l, and were an ex-smoker, as opposed to a current or non-smoker, at respective odds ratios of 1.77, 1.45, 1.71, and 1.73.
The team says: "The implication is that if cohorts in the future are dependent upon prior written consent they are likely to contain disproportionate numbers of those who have made healthy lifestyle decisions, who have previously benefited from healthcare, or those whose clinical risk factors are already well managed.
"This may have two serious consequences: first, the generalizability of observational research will be reduced; second, the effects of treatments may be variously overestimated or underestimated if those who are most unwell or are not making healthy lifestyle decisions are under-represented in study populations."
In an accompanying editorial, Cornelia Junghans and Melvyn Jones, from Royal Free and University College London Medical School in the UK, write: "Possibly, the public may decide that individual privacy is more important than the societal benefits of research, once an open debate has taken place.
"In this case, patient education may be the only way forward to ensure adequate and unbiased participation in research."
Free abstract
By Liam Davenport
05 September 2007
Heart 2007; 93: 1116-1120
MedWire News: Consent bias may impact on observational research into ischemic heart disease, with clinically important prognostic variables associated with consent preferences, say Irish researchers.
Patients' right to privacy and confidentiality has been increasingly acknowledged in recent years. Although the implications of prior written consent have been discussed in terms of healthcare professionals, public attitudes have not been widely examined, and what research has been conducted has yielded mixed results.
Researchers have expressed concerns over the potential constraints of strict consent rules on observational research, so Brian Buckley, from the National University of Ireland in Galway, and colleagues sought to determine differences between adults who consent to participating in such research and those who do not.
They examined data on a representative cohort of 1609 patients with ischemic heart disease from 35 randomized general practices identified in 2001. Baseline questionnaires were sent to 1269 participants, with follow-up medical charts up to the years 2005-2006 located for 1592 patients.
In all, 876 (69%) of the questionnaires were returned completed. Of these, 574 (65.5%) gave consent for their participation in further research, the team reports in the journal Heart.
Multiple logistic regression analysis revealed that patients were more likely to consent to participation in further research if the factors they had undergone prior percutaneous transluminal coronary angioplasty, a last recorded blood pressure of less than 140/90 mmHg, a last recorded total cholesterol level of less than 5 mmol/l, and were an ex-smoker, as opposed to a current or non-smoker, at respective odds ratios of 1.77, 1.45, 1.71, and 1.73.
The team says: "The implication is that if cohorts in the future are dependent upon prior written consent they are likely to contain disproportionate numbers of those who have made healthy lifestyle decisions, who have previously benefited from healthcare, or those whose clinical risk factors are already well managed.
"This may have two serious consequences: first, the generalizability of observational research will be reduced; second, the effects of treatments may be variously overestimated or underestimated if those who are most unwell or are not making healthy lifestyle decisions are under-represented in study populations."
In an accompanying editorial, Cornelia Junghans and Melvyn Jones, from Royal Free and University College London Medical School in the UK, write: "Possibly, the public may decide that individual privacy is more important than the societal benefits of research, once an open debate has taken place.
"In this case, patient education may be the only way forward to ensure adequate and unbiased participation in research."
Free abstract
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