John P. A. Ioannidis's research while affiliated with Stanford Medicine and other places

Publications (523)

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Both citation and funding metrics converge in shaping current perceptions of academic success. We aimed to evaluate what proportion of the most-cited USA-based biomedical scientists are funded by biomedical federal agencies and whether funded scientists are more cited than not funded ones. We linked a Scopus-based database on top-cited researchers...
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Objective To systematically assess the robustness of reported postacute SARS-CoV-2 infection health outcomes in children. Methods A search on PubMed and Web of Science was conducted to identify studies published up to 22 January 2022 that reported on postacute SARS-CoV-2 infection health outcomes in children (<18 years) with follow-up of ≥2 months...
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[This corrects the article DOI: 10.1371/journal.pmed.0020124.].
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A series of aggressive restrictive measures were adopted around the world in 2020–2022 to attempt to prevent SARS-CoV-2 from spreading. However, it has become increasingly clear the most aggressive (lockdown) response strategies may involve negative side-effects such as a steep increase in poverty, hunger, and inequalities. Several economic, educat...
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Publication selection bias undermines the systematic accumulation of evidence. To assess the extent of this problem, we survey over 26,000 meta-analyses containing more than 800,000 effect size estimates from medicine, economics, and psychology. Our results indicate that meta-analyses in economics are the most severely contaminated by publication s...
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Journals exert considerable control over letters, commentaries and online comments that criticize prior research (post-publication critique). We assessed policies (Study One) and practice (Study Two) related to post-publication critique at 15 top-ranked journals in each of 22 scientific disciplines ( N = 330 journals). Two-hundred and seven (63%) j...
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Item 10 of the Edinburgh Postnatal Depression Scale (EPDS) is intended to assess thoughts of intentional self-harm but may also elicit concerns about accidental self-harm. It does not specifically address suicide ideation but, nonetheless, is sometimes used as an indicator of suicidality. The 9-item version of the EPDS (EPDS-9), which omits item 10...
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Objectives To summarise the range, strength, and validity of reported associations between environmental risk factors and non-Hodgkin's lymphoma, and to evaluate the concordance between associations reported in meta-analyses of summary level data and meta-analyses of individual participant data. Design Umbrella review and comparison of meta-analys...
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Massive scientific productivity accompanied the COVID-19 pandemic. We evaluated the citation impact of COVID-19 publications relative to all scientific work published in 2020 to 2021 and assessed the impact on scientist citation profiles. Using Scopus data until August 1, 2021, COVID-19 items accounted for 4% of papers published, 20% of citations r...
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Background: Data on the rate and severity of SARS-CoV-2 reinfections in real-world settings are scarce and the effects of vaccine boosters on reinfection risk are unknown. Methods: In a population-level observational study, registered SARS-CoV-2 laboratory-confirmed Vojvodina residents, between March 6, 2020 and October 31, 2021, were followed f...
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Social media and new tools for engagement offer democratic platforms for enhancing constructive scientific criticism which had previously been limited. Constructive criticism can now be massive, timely, and open. However, new options have also enhanced obsessive criticism. Obsessive criticism tends to focus on one or a handful of individuals and th...
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Background COVID-19 exhibits a steep age gradient of infection fatality rate. There has been debate about whether extra protection of elderly and other vulnerable individuals (precision shielding) is feasible, and, if so, to what extent. Methods We used systematically retrieved data from national seroprevalence studies conducted in the pre-vaccina...
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Different modeling approaches can be used to calculate excess deaths for the COVID-19 pandemic period. We compared 6 calculations of excess deaths (4 previously published [3 without age-adjustment] and two new ones that we performed with and without age-adjustment) for 2020-2021. With each approach, we calculated excess deaths metrics and the ratio...
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SARS-CoV-2 Omicron variants contain many mutations in its spike receptor-binding domain, the target of all authorized monoclonal antibodies (MAbs). Determining the extent to which Omicron variants reduced MAb susceptibility is critical to preventing and treating COVID-19. We systematically reviewed PubMed and three preprint servers, last updated 11...
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Objective To assess the patterns and time trends in overall survival and progression-free survival treatment effects across randomized controlled trials (RCTs) in oncology. Study design and setting A PUBMED search for oncology network meta-analyses (NMAs) was carried (to September 30th, 2021). Relevant hazard ratios were extracted for systemic tre...
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Background: Systematic reviews of health economic evaluations (SR-HEs) provide a critical tool for synthesizing published literature to guide decision makers towards implementing evidence-based policy and healthcare practice. However, the quality of the methodology and reporting of SRs is often flawed due to insufficiencies in their design, conduct...
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Different modeling approaches can be used to calculate excess deaths for the COVID-19 pandemic period. We compared 6 calculations of excess deaths (4 previously published and two new ones that we performed with and without age-adjustment) for 2020-2021. With each approach, we calculated excess deaths metrics and the ratio R of excess deaths over re...
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Background Data on the rate and severity of SARS-CoV-2 reinfections in real-world settings are scarce and the effects of vaccine boosters on reinfection risk are unknown. Methods In a retrospective cohort study, registered SARS-CoV-2 laboratory-confirmed Vojvodina residents, between March 6, 2020 and October 31, 2021, were followed for reinfection...
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Objective To estimate the proportion of healthcare interventions tested within Cochrane Reviews that are effective according to high-quality evidence. Study design and setting We selected a random sample of 2428 (35%) of all Cochrane Reviews published between 1 January 2008 and 5 March 2021. We extracted data about interventions within these revie...
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Objective To evaluate for COVID-19 treatments without benefits in subsequent large RCTs how many of their most-cited clinical studies had declared favorable results. Study design Scopus searches (December 23, 2021) identified articles on lopinavir-ritonavir, hydroxycholoroquine, azithromycin, remdesivir, convalescent plasma, colchicine or interfer...
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Non-randomised studies assessing COVID-19 vaccine effectiveness need to consider multiple factors that may generate spurious estimates due to bias or genuinely modify effectiveness. These include pre-existing immunity, vaccination misclassification, exposure differences, testing, disease risk factor confounding, hospital admission decision, treatme...
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Importance There is concern that post-acute SARS-CoV-2 infection health outcomes (“post-COVID syndrome”) in children could be a serious problem but at the same time there is concern about the validity of reported associations between infection and long-term outcomes. Objective To systematically assess the validity of reported post-acute SARS-CoV-2...
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Importance The case fatality rate of SARS-CoV-2 has been high among residents of long-term care (LTC) facilities. It is important to know if the excess mortality persists beyond the acute infection. Objective To evaluate whether SARS-CoV-2 is associated with higher mortality after the first month from documented infection. Design We extended the...
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Background: Reproducibility is a central tenant of research. Explicit reproducibility checks are made across different disciplines trying to assess the replication of previously published studies. We aimed to synthesize the literature on reproducibility and describe its epidemiological characteristics, including how reproducibility is defined and a...
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SARS-CoV-2 Omicron variants contain many mutations in its spike receptor binding domain, the target of all authorized monoclonal antibodies (mAbs). Determining the extent to which Omicron variants reduced mAb susceptibility is critical to preventing and treating COVID-19. We systematically reviewed PubMed and three preprint servers, last updated Fe...
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This mixed design synthesis aimed to estimate the infection fatality rate (IFR) of Coronavirus Disease 2019 (COVID-19) in community-dwelling elderly populations and other age groups from seroprevalence studies. Protocol: https://osf.io/47cgb. Eligible were seroprevalence studies done in 2020 and identified by any of four existing systematic reviews...
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There are no widely accepted, quantitative definitions for the end of a pandemic like COVID‐19. The end of the pandemic due to a new virus and the transition to endemicity may be defined based on a high proportion of the global population having some immunity from natural infection or vaccination. Other considerations include diminished death toll,...
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Background: Behavioral interventions are often complex, operate at multiple levels, across settings, and employ a range of behavior change techniques. Collecting and reporting key indicators of initial trial and intervention feasibility is essential to decisions for progressing to larger-scale trials. The extent of reporting on feasibility indicato...
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Overstated generalizability (external validity) is common in research. It may coexist with inflation of the magnitude and statistical support for effects and dismissal of internal validity problems. Generalizability may be secured before attempting replication of proposed discoveries or replication may precede efforts to generalize. These opposite...
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Scientific journals may counter the misuse and misinterpretation of statistical methods by providing statistical guidance to authors. Here, we sought to assess the nature and prevalence of statistical guidance offered to authors by 15 journals (top-ranked by Impact Factor) in each of 22 scientific disciplines (N = 330 journals). For each journal, t...
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There are important questions surrounding the potential contribution of outdoor and indoor air quality in the transmission of SARS-CoV-2 and perpetuation of COVID-19 epidemic waves. Environmental health may be a critical component of COVID-19 prevention. The public health community and health agencies should consider the evolving evidence in their...
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Objective The Great Barrington Declaration (GBD) and the John Snow Memorandum (JSM), each signed by numerous scientists, have proposed hotly debated strategies for handling the COVID-19 pandemic. The current analysis aimed to examine whether the prevailing narrative that GBD is a minority view among experts is true. Methods The citation impact and...
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Mental disorders represent a worldwide public health concern. Psychotherapies and pharmacotherapies are recommended as first line treatments. However, evidence has emerged that their efficacy may be overestimated, due to a variety of shortcomings in clinical trials (e.g., publication bias, weak control conditions such as waiting list). We performed...
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Seroprevalence surveys suggest that more than a third and possibly more than half of the global population has been infected with SARS-CoV-2 by early 2022. As large numbers of people continue to be infected, the efficacy and duration of natural immunity in terms of protection against SARS-CoV-2 reinfections and severe disease is of crucial signific...
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There is ongoing debate on the COVID-19 infection fatality rate (IFR) and the impact of COVID-19 on overall population mortality. Here, we addressed these issues in a community in Germany with a major superspreader event analyzing deaths over time as well as auditing death certificates in the community.18 deaths that occurred within the first 6 mon...
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Objective To analyze distribution of “dramatic”, large treatment effects. Study Design & Setting Pareto distribution modeling of previously reported cohorts of 3,486 randomized trials (RCTs) that enrolled 1,532,459 patients and 730 non-randomized studies (NRS) enrolling 1,650,658 patients. Results We calculated the Pareto α parameter, which deter...
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Pre-registration is a research practice where a protocol is deposited in a repository before a scientific project is performed. The protocol may be publicly visible immediately upon deposition or it may remain hidden until the work is completed/published. It may include the analysis plan, outcomes, and/or information about how evaluation of perform...
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Massive scientific productivity accompanied the COVID-19 pandemic. We evaluated the citation impact of COVID-19 publications relative to all scientific work published in 2020-2021 and assessed the impact on scientist citation profiles. Using Scopus data until August 1, 2021, COVID-19 items accounted for 4% of papers published, 20% of citations rece...
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Critical scrutiny of published research is an important feature of a self-correcting scientific ecosystem. Academic journals exert considerable control over criticism submitted in the form of letters, commentaries, or online comments (post-publication peer review, PPPR). Currently, there is limited empirical data documenting how journals handle PPP...
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Importance. COVID-19 has resulted in massive production, publication and wide dissemination of clinical studies trying to identify effective treatments. However, several widely touted treatments failed to show effectiveness in large well-done randomized controlled trials (RCTs). Objective. To evaluate for COVID-19 treatments that showed no benefits...
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To make informative public policy decisions in battling the ongoing COVID-19 pandemic, it is important to know the disease prevalence in a population. There are two intertwined difficulties in estimating this prevalence based on testing results from a group of subjects. First, the test is prone to measurement error with unknown sensitivity and spec...
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The coronavirus disease 2019 (COVID-19) pandemic incited a global clinical trial research agenda of unprecedented speed and high volume. This expedited research activity in a time of crisis produced both successes and failures that offer valuable learning opportunities for the scientific community to consider. Successes include the implementation o...
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Background In this paper, we argue for Gender as a Sociocultural Variable (GASV) as a complement to Sex as a Biological Variable (SABV). Sex (biology) and gender (sociocultural behaviors and attitudes) interact to influence health and disease processes across the lifespan—which is currently playing out in the COVID-19 pandemic. This study develops...
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Background Convalescent plasma has been widely used to treat COVID-19 and is under investigation in numerous randomized clinical trials, but results are publicly available only for a small number of trials. The objective of this study was to assess the benefits of convalescent plasma treatment compared to placebo or no treatment and all-cause morta...
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Biases introduced in early-stage studies can lead to inflated early discoveries. The risk of generalizability biases (RGBs) identifies key features of feasibility studies that, when present, lead to reduced impact in a larger trial. This meta-study examined the influence of RGBs in adult obesity interventions. Behavioral interventions with a publis...
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Shortened versions of self-reported questionnaires may be used to reduce respondent burden. When shortened screening tools are used, it is desirable to maintain equivalent diagnostic accuracy to full-length forms. This manuscript presents a case study that illustrates how external data and individual participant data meta-analysis can be used to as...
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Objectives Most countries initially deployed COVID-19 vaccines preferentially in elderly populations. We aimed to evaluate whether population-level vaccine effectiveness is heralded by an increase in the relative proportion of deaths among non-elderly populations that were less covered by vaccination programs. Eligible data We collected data from...
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We assessed whether the most highly cited studies in emotion research reported larger effect sizes compared with meta-analyses and the largest studies on the same question. We screened all reports with at least 1,000 citations and identified matching meta-analyses for 40 highly cited observational studies and 25 highly cited experimental studies. H...
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Florian Naudet and co-authors discuss strengthening requirements for sharing clinical trial data.
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Recent, high-profile, large-scale, preregistered failures to replicate uncover that many highly-regarded experiments are ‘false positives;’ that is, statistically significant results of underlying null effects. Large surveys of research reveal that statistical power is often low and inadequate. When the research record includes selective reporting,...
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Objective To evaluate whether the COVID-19 experts who appear most frequently in media have high citation impact for their research overall, and for their COVID-19 peer-reviewed publications in particular and to examine the representation of women among such experts. Design Cross-linking of data sets of most highly visible COVID-19 media experts w...
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With the establishment of large biobanks, discovery of single nucleotide variants (SNVs, also known as single nucleotide polymorphisms (SNVs)) associated with various phenotypes has accelerated. An open question is whether genome-wide significant SNVs identified in earlier genome-wide association studies (GWAS) are replicated in later GWAS conducte...
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We examined the extent to which the scientific workforce in different fields was engaged in publishing COVID-19-related papers. According to Scopus (data cut, 1 August 2021), 210 183 COVID-19-related publications included 720 801 unique authors, of which 360 005 authors had published at least five full papers in their career and 23 520 authors were...
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Introduction Inflammatory arthritis (IA) conditions, including rheumatoid arthritis, psoriatic arthritis and axial spondyloarthritis, are characterised by inflammatory infiltration of the joints. Biological disease-modifying antirheumatic drugs (bDMARDs) and targeted synthetic disease-modifying antirheumatic drugs (tsDMARDs), respectively, reduce t...
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The emergence of new cell and gene-based therapies (CGTs) utilizing innovative technologies has recently intensified. Long-standing efforts in publicly funded biomedical research have resulted in breakthrough therapeutic approaches for patients with devastating and life-threatening diseases. Transformative gene-based therapeutic tools include human...
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p>Objective: To evaluate, across multiple sample sizes, the degree that data-driven methods result in (1) optimal cutoffs different from population optimal cutoff and (2) bias in accuracy estimates. Study design and setting: A total of 1,000 samples of sample size 100, 200, 500 and 1,000 each were randomly drawn to simulate studies of different sam...
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Strategies for the use of COVID‐19 vaccines in children and young adults (in particular university students) are hotly debated and important to optimize. As of late August 2021, recommendations on the use of these vaccines in children vary across different countries. Recommendations are more uniform for vaccines in young adults, but vaccination upt...
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People receiving COVID-19 vaccines may subsequently markedly increase their previously suppressed exposure risk. A simple model can evaluate the benefit of vaccination to the vaccinated (index) person and others exposed to that person; and calculate the amount of risk compensation required to eliminate all the benefits or to halve the benefit. As s...
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The objectives of the study were to calculate the standardised mortality rates (SMRs) for COVID-19 in European Union/European Economic Area countries plus the UK and Switzerland and to evaluate the correlation between SMRs and selected indicators in the first versus the subsequent waves until 23 June 2021. We used indirect standardisation (using It...
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Effective collaboration and mentorship are essential to success in a career of health research. We summarize our conversation with Dr. John Ioannidis, professor at Stanford University, author of the most accessed manuscript in the history of the Public Library of Science, and one of the most cited scientists in history. Dr. Ioannidis was invited fo...
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Objective: In 2019, Ward et al. proposed a method to adjust BMI calculated from self-reported weight and height for bias relative to measured data. They did not evaluate the adjusted values relative to measured BMI values for the same individuals. Methods: A large data set (n = 37,439) with both measured and self-reported weight and height was r...
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Background. Most countries initially deployed COVID-19 vaccines preferentially in elderly populations. Population-level vaccine effectiveness may be heralded by an increase in the proportion of deaths among non-elderly populations that were less covered by vaccination programs. Methods. We collected data from 40 countries on age-stratified COVID-19...
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Background: The infection fatality rate (IFR) of Coronavirus Disease 2019 (COVID-19) varies widely according to age and residence status. Purpose: Estimate the IFR of COVID-19 in community-dwelling elderly populations and other age groups from seroprevalence studies. Study protocol: https://osf.io/47cgb. Data Sources: Seroprevalence studies done in...
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Background The validity of observational studies and their meta-analyses is contested. Here, we aimed to appraise thousands of meta-analyses of observational studies using a pre-specified set of quantitative criteria that assess the significance, amount, consistency, and bias of the evidence. We also aimed to compare results from meta-analyses of o...
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Replication studies that contradict prior findings may facilitate scientific self-correction by triggering a reappraisal of the original studies; however, the research community’s response to replication results has not been studied systematically. One approach for gauging responses to replication results is to examine how they affect citations to...
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We introduce and evaluate three tests for publication selection bias based on excess statistical significance. The proposed tests incorporate heterogeneity explicitly in the formulas for expected and excess statistical significance. We calculate the expected proportion of statistically significant findings in the absence of selective reporting or p...
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Objective: We developed a research usefulness tool collating published criteria and examined if randomised controlled trials (RCTs) addressing preterm birth were useful. Search Strategy: Cochrane library. Selection Criteria: Published RCTs within 56 preterm birth Cochrane reviews. Data Collection and Analysis: A usefulness tool was developed with e...
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Objectives To conduct an umbrella review of therapeutic studies relevant to emergency medicine, analyzing patterns in effect size, power and signals of potential bias across an entire field of clinical research. Methods We combined topic and journal-driven searches of PUBMED and Google Scholar for published articles of systematic reviews and meta-...