Inadequate Dissemination of Phase I Trials: A Retrospective Cohort Study

François Chapuis and colleagues examine a cohort of clinical trial protocols approved by French ethics committees, and show that Phase I trials are less frequently published than other types of trials

Impact of funding on biomedical research: a retrospective cohort study

BACKGROUND: Public funding is aimed at facilitating the initiation, completion and publication of research study protocols. However, no evaluation is made to investigate the impact of grant success on the conduct of biomedical research. It is therefore of great interest to compare the fate of funded protocols versus not funded: Are they initiated? Are they completed? Did the results confirm the hypothesis? Were they published? The objective was to investigate the fate of protocols submitted for funding, whether they were funded or not. METHODS: Retrospective cohort study of protocols submitted for funding to the Greater Lyon regional scientific committee in 1997. Initial characteristics of protocols (design, study size, investigator status) were abstracted from archives, and follow-up characteristics (initiation, completion and publication) from a mailed questionnaire to the principal investigators. RESULTS: Among the 142 submitted protocols, follow-up information was available for 114 (80%). As a whole, 38% of studies were funded by the Greater Lyon research committee. The rate of initiation varied from 62% for studies with no acknowledged funding to 100% for studies with both committee and other simultaneous funding. When initiated, the rate of completion was 62% for studies with at least one funding and 40% for studies without acknowledged funding. When completed, publication was reached for 77% of studies with either committee or external funding, for 58% of studies without acknowledged funding and for 37% of studies with both committee and external funding. CONCLUSION: Some protocols submitted for funding were initiated and completed without any funding declared. To our understanding this mean that not all protocols submitted really needed funding and also that health care facilities are unaware that they implicitly financially support and pay for biomedical research

Typology and Dynamics of Heavier Drinking Styles in Great Britain: 1978-2010.

AIMS: To identify a typology of heavier drinking styles in Great Britain and to identify socio-demographic trends in the typology over the period 1978-2010. METHODS: We applied multiple correspondence analysis and agglomerative hierarchical clustering to beverage-specific quantity-frequency measures of alcohol consumption in the repeated cross-sectional General Lifestyle Survey of Great Britain, 1978-2010. The cluster analysis focuses on the 60,043 adult respondents over this period reporting average drinking levels above the UK Government guidelines. We projected sex, age, income, education, socio-economic status and tobacco consumption variables onto the clusters to inspect socio-demographic trends in heavier drinking. RESULTS: We identified four stable clusters of heavier drinking: (a) high volume beer; (b) beer and spirit combination; (c) all beverage and (d) wine and spirit only. The socio-demographic characteristics of the clusters were distinct from both each other and the general population. However, all clusters had higher median incomes and higher smoking rates than the population. Increases in the prevalence of heavier drinking were driven by a 5-fold increase in the contribution of the female-dominated, wine and spirit only cluster. CONCLUSIONS: Recent changes in per capita alcohol consumption in Great Britain occurred within the context of a stable typology of heavier drinking styles and shifting socio-demographics. Identifying these trends is essential to better understand how drinking cultures develop over time and where potentially problematic drinking styles may emerge. Our findings suggest that careful attention to patterns and cultures of consumption is more important than relying on headline consumption data, for both understanding drinking behaviours and targeting interventions. SHORT SUMMARY: This analysis of alcohol consumption survey data identifies four styles of heavier drinking in Great Britain, which remain unchanged over the period 1978-2010. The socio-demographic characteristics of the drinking styles are distinct from both each other and the general population, with increased participation of female and older drinkers over time

What do the JAMA editors say when they discuss manuscripts that they are considering for publication? Developing a schema for classifying the content of editorial discussion

<p>Abstract</p> <p>Background</p> <p>In an effort to identify previously unrecognized aspects of editorial decision-making, we explored the words and phrases that one group of editors used during their meetings.</p> <p>Methods</p> <p>We performed an observational study of discussions at manuscript meetings at <it>JAMA</it>, a major US general medical journal. One of us (KD) attended 12 editorial meetings in 2003 as a visitor and took notes recording phrases from discussion surrounding 102 manuscripts. In addition, editors attending the meetings completed a form for each manuscript considered, listing the reasons they were inclined to proceed to the next step in publication and reasons they were not (DR attended 4/12 meetings). We entered the spoken and written phrases into NVivo 2.0. We then developed a schema for classifying the editors' phrases, using an iterative approach.</p> <p>Results</p> <p>Our classification schema has three main themes: science, journalism, and writing. We considered 2,463 phrases, of which 87 related mainly to the manuscript topic and were not classified (total 2,376 classified). Phrases related to science predominated (1,274 or 54%). The editors, most of whom were physicians, also placed major weight on goals important to JAMA's mission (journalism goals) such as importance to medicine, strategic emphasis for the journal, interest to the readership, and results (729 or 31% of phrases). About 16% (n = 373) of the phrases used related to writing issues, such as clarity and responses to the referees' comments.</p> <p>Conclusion</p> <p>Classification of editorial discourse provides insight into editorial decision making and concepts that need exploration in future studies.</p

The activity of French Research Ethics Committees and characteristics of biomedical research protocols involving humans: a retrospective cohort study

BACKGROUND: Clinical trials throughout the world must be evaluated by research ethics committees. No one has yet attempted to clearly quantify at the national level the activity of ethics committees and describe the characteristics of the protocols submitted. The objectives of this study were to describe 1) the workload and the activity of Research Ethics Committees in France, and 2) the characteristics of protocols approved on a nation-wide basis. METHODS: Retrospective cohort of 976 protocols approved by a representative sample of 25/48 of French Research Ethics Committees in 1994. Protocols characteristics (design, study size, investigator), number of revisions requested by the ethics committee before approval, time to approval and number of amendments after approval were collected for each protocol by trained research assistant using the committee's files and archives. RESULTS: Thirty-one percent of protocols were approved with no modifications requested in 16 days (95% CI: 14–17). The number of revisions requested by the committee, and amendments submitted by the investigator was on average respectively 39 (95% CI: 25–53) and 37 (95% CI: 27–46), per committee and per year. When revisions were requested, the main reasons were related to information to the patient (28%) and consent modalities (18%). Drugs were the object of research in 68% of the protocols examined. The majority of the research was national (80%) with a predominance of single-centre studies. Workload per protocol has been estimated at twelve and half hours on average for administrative support and at eleven and half hours for expertise. CONCLUSION: The estimated workload justifies specific and independent administrative and financial support for Research Ethics Committees

Implementing clinical trial data sharing requires training a new generation of biomedical researchers

Data sharing enhances the value of medical research and builds trust in clinical trials, but more biomedical researchers need to be trained in these approaches, which include meta-research, data science and ethical, legal and social issues

Systematic Review of the Empirical Evidence of Study Publication Bias and Outcome Reporting Bias

BACKGROUND: The increased use of meta-analysis in systematic reviews of healthcare interventions has highlighted several types of bias that can arise during the completion of a randomised controlled trial. Study publication bias has been recognised as a potential threat to the validity of meta-analysis and can make the readily available evidence unreliable for decision making. Until recently, outcome reporting bias has received less attention. METHODOLOGY/PRINCIPAL FINDINGS: We review and summarise the evidence from a series of cohort studies that have assessed study publication bias and outcome reporting bias in randomised controlled trials. Sixteen studies were eligible of which only two followed the cohort all the way through from protocol approval to information regarding publication of outcomes. Eleven of the studies investigated study publication bias and five investigated outcome reporting bias. Three studies have found that statistically significant outcomes had a higher odds of being fully reported compared to non-significant outcomes (range of odds ratios: 2.2 to 4.7). In comparing trial publications to protocols, we found that 40-62% of studies had at least one primary outcome that was changed, introduced, or omitted. We decided not to undertake meta-analysis due to the differences between studies. CONCLUSIONS: Recent work provides direct empirical evidence for the existence of study publication bias and outcome reporting bias. There is strong evidence of an association between significant results and publication; studies that report positive or significant results are more likely to be published and outcomes that are statistically significant have higher odds of being fully reported. Publications have been found to be inconsistent with their protocols. Researchers need to be aware of the problems of both types of bias and efforts should be concentrated on improving the reporting of trials

Premature Discontinuation of Prospective Clinical Studies Approved by a Research Ethics Committee - A Comparison of Randomised and Non-Randomised Studies.

Premature discontinuation of clinical studies affects about 25% of randomised controlled trials (RCTs) which raises concerns about waste of scarce resources for research. The risk of discontinuation of non-randomised prospective studies (NPSs) is yet unclear. To compare the proportion of discontinued studies between NPSs and RCTs that received ethical approval. We systematically surveyed prospective longitudinal clinical studies that were approved by a single REC in Freiburg, Germany between 2000 and 2002. We collected study characteristics, identified subsequent publications, and surveyed investigators to elucidate whether a study was discontinued and, if so, why. Of 917 approved studies, 547 were prospective longitudinal studies (306 RCTs and 241 NPSs). NPSs were on average smaller than RCTs, more frequently single centre and pilot studies, and less frequently funded by industry. NPSs were less frequently discontinued than RCTs: 32/221 (14%) versus 78/288 (27%, p&lt;0.001, missing data excluded). Poor recruitment was the most frequent reason for discontinuation in both NPSs (36%) and RCTs (37%). Compared to RCTs, NPSs were at lower risk for discontinuation. Measures to reliably predict, sustain, and stimulate recruitment could prevent discontinuation of many RCTs but also of some NPSs

Extent of non-publication in cohorts of studies approved by research ethics committees or included in trial registries

BACKGROUND: The synthesis of published research in systematic reviews is essential when providing evidence to inform clinical and health policy decision-making. However, the validity of systematic reviews is threatened if journal publications represent a biased selection of all studies that have been conducted (dissemination bias). To investigate the extent of dissemination bias we conducted a systematic review that determined the proportion of studies published as peer-reviewed journal articles and investigated factors associated with full publication in cohorts of studies (i) approved by research ethics committees (RECs) or (ii) included in trial registries. METHODS AND FINDINGS: Four bibliographic databases were searched for methodological research projects (MRPs) without limitations for publication year, language or study location. The searches were supplemented by handsearching the references of included MRPs. We estimated the proportion of studies published using prediction intervals (PI) and a random effects meta-analysis. Pooled odds ratios (OR) were used to express associations between study characteristics and journal publication. Seventeen MRPs (23 publications) evaluated cohorts of studies approved by RECs; the proportion of published studies had a PI between 22% and 72% and the weighted pooled proportion when combining estimates would be 46.2% (95% CI 40.2%-52.4%, I2 = 94.4%). Twenty-two MRPs (22 publications) evaluated cohorts of studies included in trial registries; the PI of the proportion published ranged from 13% to 90% and the weighted pooled proportion would be 54.2% (95% CI 42.0%-65.9%, I2 = 98.9%). REC-approved studies with statistically significant results (compared with those without statistically significant results) were more likely to be published (pooled OR 2.8; 95% CI 2.2-3.5). Phase-III trials were also more likely to be published than phase II trials (pooled OR 2.0; 95% CI 1.6-2.5). The probability of publication within two years after study completion ranged from 7% to 30%. CONCLUSIONS: A substantial part of the studies approved by RECs or included in trial registries remains unpublished. Due to the large heterogeneity a prediction of the publication probability for a future study is very uncertain. Non-publication of research is not a random process, e.g., it is associated with the direction of study findings. Our findings suggest that the dissemination of research findings is biased