ASSESSING THE UNRELIABILITY OF THE MEDICAL LITERATURE: A RESPONSE TO WHY MOST PUBLISHED RESEARCH FINDINGS ARE FALSE

A recent article in this journal (Ioannidis JP (2005) Why most published research findings are false. PLoS Med 2: e124) argued that more than half of published research findings in the medical literature are false. In this commentary, we examine the structure of that argument, and show that it has three basic components: 1)An assumption that the prior probability of most hypotheses explored in medical research is below 50%. 2)Dichotomization of P-values at the 0.05 level and introduction of a “bias” factor (produced by significance-seeking), the combination of which severely weakens the evidence provided by every design. 3)Use of Bayes theorem to show that, in the face of weak evidence, hypotheses with low prior probabilities cannot have posterior probabilities over 50%. Thus, the claim is based on a priori assumptions that most tested hypotheses are likely to be false, and then the inferential model used makes it impossible for evidence from any study to overcome this handicap. We focus largely on step (2), explaining how the combination of dichotomization and “bias” dilutes experimental evidence, and showing how this dilution leads inevitably to the stated conclusion. We also demonstrate a fallacy in another important component of the argument –that papers in “hot” fields are more likely to produce false findings. We agree with the paper’s conclusions and recommendations that many medical research findings are less definitive than readers suspect, that P-values are widely misinterpreted, that bias of various forms is widespread, that multiple approaches are needed to prevent the literature from being systematically biased and the need for more data on the prevalence of false claims. But calculating the unreliability of the medical research literature, in whole or in part, requires more empirical evidence and different inferential models than were used. The claim that “most research findings are false for most research designs and for most fields” must be considered as yet unproven

Irresponsible marketing and the need to support pro-sustainable production and consumption

Globally, organisations and consumers face an array of economic, environmental, and social sustainability challenges. The UN Sustainable Development Goals (SDGs) assist by providing guidance for appreciating and responding to these challenges. Marketers also have an important role to play in promoting positive sustainable attitudes and behaviour in both consumer and corporate contexts. Increasingly sophisticated marketing capabilities, combined with enhanced understanding of consumer psychology, mean that marketers have unprecedented ability to positively influence public opinion and promote positive social and environmental behaviours. However, this capability is frequently used irresponsibly in the pursuit of profit and political goals, with disregard for sustainable outcomes. Irresponsible marketing, including sustainability washing, misleads consumers and governments about the sustainability credentials of these organisations’ products or services. This undermines SDG 12 sustainable consumption and production, as well as the other SDGs. This paper discusses the need for marketers to be more proactive in promoting sustainability and informing irresponsible marketing regulation. Critical avenues for future research are also identified

Evidence of Lung Function for Stratification of Cardiovascular Disease Risk

Among adults in the United States, the prevalence of reduced lung function including obstructive and restrictive lung disease is about 20%, representing an over 40 million adults. Persons with reduced lung function often demonstrate chronic systemic inflammation, such as from elevated levels of C-reactive protein. Substantial data suggests that inflammation may have a significant role in the association between reduced lung function and cardiovascular disease (CVD); however, how reduced lung function predicts CVD as risk modification remains largely unknown. Poor lung function has been shown to be a better predictor of all-cause and cardiac-specific mortality than established risk factors such as serum cholesterol, and CVD is the leading cause of mortality among those with impaired lung function. The exact mechanism of atherosclerosis is not clear, but persistent low grade inflammation is considered as one of the culprits in clot formation. The initial presentation of coronary heart disease is either myocardial infarction or sudden death in approximately half of the individuals. Unfortunately, conventional risk factor assessment predicts only 65-80% of future cardiovascular events, leaving many middle-aged and older individuals to manifest a major cardiovascular event despite being classified low risk by the Framingham risk estimates

Understanding and reporting odds ratios as rate-ratio estimates in case-control studies

Background: We noted that there remains some confusion in the health-science literature on reporting sample odds ratios as estimated rate ratios in case-control studies. Methods: We recap historical literature that definitively answered the question of when sample odds ratios (ORs) from a case-control study are consistent estimators for population rate ratios. We use numerical examples to illustrate the magnitude of the disparity between sample ORs in a case-control study and population rate ratios when sufficient conditions for them to be equal are not satisfied. Results: We stress that in a case-control study, sampling controls from those still at risk at the time of outcome event of the index case is not sufficient for a sample OR to be a consistent estimator for an intelligible rate ratio. In such studies, constancy of the exposure prevalence together with constancy of the hazard ratio (HR) (i.e., the instantaneous rate ratio) over time is sufficient for this result if sampling time is not controlled; if time is controlled, constancy of the HR will suffice. We present numerical examples to illustrate how failure to satisfy these conditions adds a small systematic error to sample ORs as estimates of population rate ratios. Conclusions: We recommend that researchers understand and critically evaluate all conditions used to interpret their estimates as consistent for a population parameter in case-control studies

Inflammatory and Coagulation Biomarkers and Mortality in Patients with HIV Infection

Analyzing biomarker data from participants in a previous randomized controlled trial of continuous versus interrupted HIV treatment (the SMART trial), James Neaton and colleagues find that mortality was related to IL-6 and fibrin D-dimers

Prospective Associations of Coronary Heart Disease Loci in African Americans Using the MetaboChip: The PAGE Study

Background: Coronary heart disease (CHD) is a leading cause of morbidity and mortality in African Americans. However, there is a paucity of studies assessing genetic determinants of CHD in African Americans. We examined the association of published variants in CHD loci with incident CHD, attempted to fine map these loci, and characterize novel variants influencing CHD risk in African Americans. Methods and Results: Up to 8,201 African Americans (including 546 first CHD events) were genotyped using the MetaboChip array in the Atherosclerosis Risk in Communities (ARIC) study and Women's Health Initiative (WHI). We tested associations using Cox proportional hazard models in sex- and study-stratified analyses and combined results using meta-analysis. Among 44 validated CHD loci available in the array, we replicated and fine-mapped the SORT1 locus, and showed same direction of effects as reported in studies of individuals of European ancestry for SNPs in 22 additional published loci. We also identified a SNP achieving array wide significance (MYC: rs2070583, allele frequency 0.02, P = 8.1×10−8), but the association did not replicate in an additional 8,059 African Americans (577 events) from the WHI, HealthABC and GeneSTAR studies, and in a meta-analysis of 5 cohort studies of European ancestry (24,024 individuals including 1,570 cases of MI and 2,406 cases of CHD) from the CHARGE Consortium. Conclusions: Our findings suggest that some CHD loci previously identified in individuals of European ancestry may be relevant to incident CHD in African Americans

Marked Reduction in Prevalence of Malaria Parasitemia and Anemia in HIV-Infected Pregnant Women Taking Cotrimoxazole With Or Without Sulfadoxine-Pyrimethamine Intermittent Preventive Therapy during Pregnancy in Malawi

Background. Effectiveness of cotrimoxazole (CTX) compared with sulfadoxine-pyrimethamine (SP) intermittent-preventive-therapy (IPTp) for malaria in HIV-infected pregnant women is unknown. We examined effectiveness of CTX with or without SP-IPTp versus SP-IPTp at reducing malaria parasitemia and anemia