Compliance of clinical trial registries with the World Health Organization minimum data set : a survey

BACKGROUND: Since September 2005 the International Committee of Medical Journal Editors has required that trials be registered in accordance with the World Health Organization (WHO) minimum dataset, in order to be considered for publication. The objective is to evaluate registries' and individual trial records' compliance with the 2006 version of the WHO minimum data set. METHODS: A retrospective evaluation of 21 online clinical trial registries (international, national, specialty, pharmaceutical industry and local) from April 2005 to February 2007 and a cross-sectional evaluation of a stratified random sample of 610 trial records from the 21 registries. RESULTS: Among 11 registries that provided guidelines for registration, the median compliance with the WHO criteria were 14 out of 20 items (range 6 to 20). In the period April 2005-February 2007, six registries increased their compliance by six data items, on average. None of the local registry websites published guidelines on the trial data items required for registration. Slightly more than half (330/610; 54.1%, 95% CI 50.1% - 58.1%) of trial records completed the contact details criteria while 29.7% (181/610, 95% CI 26.1% - 33.5%) completed the key clinical and methodological data fields. CONCLUSION: While the launch of the WHO minimum data set seemed to positively influence registries with better standardisation of approaches, individual registry entries are largely incomplete. Initiatives to ensure quality assurance of registries and trial data should be encouraged. Peer reviewers and editors should scrutinise clinical trial registration records to ensure consistency with WHO's core content requirements when considering trial-related publications

Patient preferences and treatment safety for uncomplicated vulvovaginal candidiasis in primary health care

<p>Abstract</p> <p>Background</p> <p>Vaginitis is a common complaint in primary care. In uncomplicated candidal vaginitis, there are no differences in effectiveness between oral or vaginal treatment. Some studies describe that the preferred treatment is the oral one, but a Cochrane's review points out inconsistencies associated with the report of the preferred way that limit the use of such data. Risk factors associated with recurrent vulvovaginal candidiasis still remain controversial.</p> <p>Methods/Design</p> <p>This work describes a protocol of a multicentric prospective observational study with one year follow up, to describe the women's reasons and preferences to choose the way of administration (oral vs topical) in the treatment of not complicated candidal vaginitis. The number of women required is 765, they are chosen by consecutive sampling. All of whom are aged 16 and over with vaginal discharge and/or vaginal pruritus, diagnosed with not complicated vulvovaginitis in Primary Care in Madrid.</p> <p>The main outcome variable is the preferences of the patients in treatment choice; secondary outcome variables are time to symptoms relief and adverse reactions and the frequency of recurrent vulvovaginitis and the risk factors. In the statistical analysis, for the main objective will be descriptive for each of the variables, bivariant analysis and multivariate analysis (logistic regression).. The dependent variable being the type of treatment chosen (oral or topical) and the independent, the variables that after bivariant analysis, have been associated to the treatment preference.</p> <p>Discussion</p> <p>Clinical decisions, recommendations, and practice guidelines must not only attend to the best available evidence, but also to the values and preferences of the informed patient.</p

Bibliometric analyses along cumulative meta-analyses : the Life Cycle of Evidence in Cancer Care (LIFE CYCLE)

Background: The LIFE CYCLE study aims to identify the key milestones in the life cycle of evidence of 9 novel chemotherapy agents, approved in Canada between 1992 and 2002 for metastatic breast and non small cell lung (NSCLC) cancers, using cumulative meta-analyses and bibliometric analyses. Objective: Bibliometrics is used to describe patterns of publications. This analysis has been used to complement the statistical and clinical data of the larger study. Methods: Several information sources were searched: i) Science Citation Index (SCI) for cited references of all included studies; ii) MEDLINE for editorials, commentaries and narrative reviews for information from opinion leaders; iii) Internet and MEDLINE for clinical guidelines; and iv) hand-search of general and cancer specific textbooks in oncology. We present analyses of vinorelbine in NSCLC as a case-study. Results: Nine studies were located for the meta-analysis pertaining to vinorelbine therapy published between 1994 and 2002, two studies presenting duplicate publications. 756 articles in SCI cited the 9 studies above. In MEDLINE, editorial, comment and narrative review articles were located, identifying 1 comment and 145 narrative reviews. Important recommendations about the use of vinorelbine were identified in nine textbooks from 1992-2002. Preliminary analysis identified the Le Chevalier study, first published in Feb 1994 (2 publications, 1994 and 1996), significantly supporting vinorelbine use, accounted for 509 (67%) of the cited references dominating the other trials in terms of research payback. Heath Canada and FDA approvals for vinorelbine were May and Dec 1994 respectively. In 1996 the citations were 10% (53/509) and peaked in 2001 (14%) when the Le Chevalier six year follow-up results were published. From 1996 onwards majority of textbooks reported vinorelbine therapy as standard first line treatment for NSCLC. Conclusion: This case study indicates that the life cycle of evidence in metastatic lung cancer may evolve more rapidly compared to Antman et als findings in treatments for myocardial infarction (1992). New agents are adopted rapidly and recommendations are published within 2 years of major research results. Bibliometric analyses alongside cumulative meta-analyses are useful in understanding the time it takes for research to feed into clinical recommendations

Valutare la qualit&#224; delle informazioni raccolte nei registri dei protocolli dei trial

Introduzione. Nel 2004 tutte le riviste del International Committee of Medical Journal Editors hanno concordato di adottare una politica di registrazione dei trial come parziale soluzione al problema del publication bias. Molte agenzie governative (UK DOH, CIHR, AIFA, ecc) hanno favorito lo sviluppo di registri di protocolli di trial clinici e li supportano finanziariamente. Malgrado questo interesse poco si sa riguardo al tipo ed alla completezza delle informazioni contenute nei registri dei trial. I nostri obiettivi sono: i) determinare il tipo di informazioni contenute nei registri dei protocolli dei trial; ii) valutare la qualit\ue0 delle informazioni; iii) confrontare i registri per informazioni contenute e iv) identificare una struttura ottimale dei dati. Materiali e metodi. Nel 2005 abbiamo effettuato uno studio che prevedeva il campionamento randomizzato di protocolli di trial da tre registri internazionali, ClinicalTrials. gov, NCI's PDQ Database e ISRCTN Register. Sono stati inclusi tutti i trial senza esclusioni relativamente a malattia, condizione medica o problematica del servizio sanitario, stato di avanzamento del trial, disegno di studio. I protocolli sono stati valutati attraverso una checklist di 30 item desiderabili raggruppati in 5 categorie: informazioni identificative, dettagli clinici, finanziamento, informazioni per contattare gli investigatori e form di raccolta dati. Risultati. \uc8 stato effettuato un pilota su 45 record (15 da ogni registro). La qualit\ue0 delle informazioni contenute era generalmente bassa (mediana: 16 item presenti; range: 10-22 per record)e variava considerevolmente tra registri. ClinicalTrial.gov (mediana 17) e NCIPDQ (mediana 18) contenevano pi\uf9 informazioni rispetto a ISRTCN (mediana 13) (ClinicalTrial.gov vs. NCIPDQ p=0. 79; ClinicalTrial.gov vs. ISRTCN p<0. 001; NCIPDQ vs. ISRTCN p<0. 001). In particolare i record erano poveri di informazioni riguardanti i dettagli clinici (item: outcome primario; date di inizio e termine dell'arruolamento) e informazioni di contatto (item: indirizzo completo; fax). Nessuno dei protocolli forniva copie dei form di raccolta dati. Al momento \ue8 in corso l'analisi di 600 nuovi record campionati casualmente dalle seguenti 5 tipologie di registri: internazionali, industria farmaceutica, nazionali (tra cui l'Osservatorio Nazionale per la Sperimentazione sui Medicinali), di specialit\ue0 e di singole istituzioni. Conclusioni. Malgrado i criteri di desiderabilit\ue0 inclusi nella checklist non fossero particolarmente stringenti, i risultati preliminari mostrano una considerevole variabilit\ue0 nel tipo di dati disponibili nei registri dei protocolli dei trial e una qualit\ue0 delle informazioni non soddisfacente. I risultati suggeriscono che vi sia la necessit\ue0 di aumentare la standardizzazione del tipo di dati raccolti per migliorare un informazione che costituisce un bene pubblico essenziale

Cumulative meta-analysis to determine key milestones in the Life Cycle of Evidence in Cancer Care

Background: Despite new advances in science, there is often a considerable lag between the generation of important research findings and their use by health care professionals. Objective: The purpose of LIFE CYCLE is to investigate the relative role of evidence and other factors in determining clinical recommendations and practice in cancer control. Metastatic breast and non small cell lung (NSCLC) cancers were chosen as case studies. All novel chemotherapy agents (NCA) approved for use in Canada between 1992 and 2002 were considered (n=9). Methods: We conducted cumulative meta-analyses of efficacy vinorelbine and taxanes (paclitaxel and docetaxel) in NSCLC from 1992-2002 replicating Antman et al. For each included randomized trial (RCT) we considered all types of publications, including abstracts from conference proceedings and subsequent journal publication(s). Cumulative evidence has been used in meta-analyses over sequential time windows (Folmann method). Additionally, bibliometric analyses have been performed to look at the payback (e.g. editorial, narrative review, textbooks and guidelines), and identify key milestones in the life cycle of evidence. Finally, we will plot the full body of research against the 1992-2002 use of the vinorelbine and taxanes in Ontario Regional Cancer Centers. Results: Vinorelbine: Out of 58 potentially eligible abstracts or full publications of RCTs, 7 RCTs were identified that provided meaningful comparisons and sufficient information to be included in cumulative meta-analysis. Of these, Le Chevalier (1994) was the first RCT that significantly supported the use of vinorelbine. Combining Le Chevalier's results with the other RCTs provided a pooled summary point that over time consistently favoured a survival advantage but confidence intervals crossed the null value at all times. Nevertheless, Le Chevalier had a strong literature payback, dominating the other trials. Taxanes: Out of 101 potentially eligible reports, only 13 provided meaningful comparisons and sufficient information. The pooled data analysis reached significance in 2002, when 8 RCTs results were available. Conclusions: This study demonstrates the relatively small pool of RCT evidence for NCAs. These two commonly used NCAs demonstrate different patterns of evolution of evidence and it is also reflected in their different citation patterns

Cumulative meta-analysis to determine key milestones in the Life Cycle of Evidence in Cancer Care

Background: Science progresses through a series of paradigms that are held to be true until they are replaced by a better approximation of reality. Despite new advances in science, there is often a considerable lag between the generation of important research findings and the use of this knowledge by health care professionals. Objective: The purpose of LIFE CYCLE-ECC is to investigate the relative role of evidence and other factors (e.g. funding approval, drug industry promotion, consumer advocacy) in determining clinical recommendations and practice in cancer control. Metastatic breast cancer and non small cell lung cancer were chosen as case studies on which to base the study. All novel chemotherapy agents (NCA) approved for use in Canada between 1992 and 2002 were considered. Methods: We are conducting cumulative meta-analyses of efficacy of each identified NCA (n=13) following the model of Antman et al.[1] For each included trial we will consider all types of related publications, starting with abstracts from conference proceedings, to subsequent journal publication(s). Cumulative evidence will be used in meta-analyses over sequential time windows. In addition, bibliometric analyses are being performed to look at the payback (e.g. editorial, narrative review), in order to identify key milestones in the life cycle of evidence, which result in translation into recommendations. Finally, we will plot the full body of research against the actual use of the NCAs in Ontario Regional Cancer Centers from 1992-2002. Follow-up qualitative analyses using focus groups with key stakeholders will be performed to better understand influences for practice decisions in Ontario. Results: Currently we are screening all eligible papers. With the large number of documents involved, this study outlines the necessity to establish the methodology to manage all the quantitative and qualitative information in order to guarantee feasibility. Potential pitfalls include: identifying a coherent starting point for the analysis; tracing the research findings forwards versus backwards; coping with and storing the enormous number of papers involved; develop new meta-analytic approaches to deal with a body of research including multiple drugs and outcomes at discrete times of research; develop ways to fully utilize bibliometric citation analysis and the cumulative rates analysis; presenting the findings in a multi-dimension document. Conclusions: This research will make a major contribution to our understanding of the way results of clinical research eventually feed through into application and which key milestones are most influential. However before embarking on such a large-scale, multi-level study, many ideas and methodological issues must be explored and resolved

Assessing the quality of information recorded on trial registries

Background: In 2004 all ICMJE member journals agreed to adopt a trial registrations policy as one solution to publication bias. The value of trial registries (TRs) has been well established and is supported by funding and government agencies. Yet there is little focus on the type and completeness of data in existing TRs. Objective: Our objectives were to, i) determine the type of data recorded in TRs, ii) assess their quality, iii) compare structure and content of different TRs, and iv) to identify optimal data structures for them. Design: In January 2005, a random sample of trial records was extracted from three international TRs ClinicalTrials.gov, NCI's PDQ Database and ISRCTN Register. No restrictions were placed on trial status, design or medical area, although some TRs adopted inclusion criteria. Records were assessed using a quality checklist consisting of 30 desirable items grouped into five categories, identifying information, trial details, funding, contact details and data collection forms. Results: A pilot study assessing 45 records (15 from each register) was undertaken. The overall quality was poor (median: 16 range: 10-22 items completed per record) and varied considerably across TRs. ClinicalTrial.gov (median 17) and NCIPDQ (median 18) faired better than ISRTCN (median 13) (ClinicalTrial.gov vs. NCIPDQ p=0.79; ClinicalTrial.gov vs. ISRTCN p<0.001; NCIPDQ vs. ISRTCN p<0.001). Records fell short of providing complete data in the category of trial details (items: primary outcome; key trial dates) and contact details (items: full address; fax). A copy of the study data collection form was not included in any record. Results from the definitive study will be available for presentation. Conclusions: Although our quality criteria were not stringent, the preliminary results show considerable variation in the data available in current TRs and an unsatisfactory quality of desirable requirements for trial protocols. The results suggest that there is room for standardization of the type of data recorded in TRs to provide better and more complete essential public information

Assessing the quality of information recorded on trial registries

Background: In 2004 all ICMJE member journals agreed to adopt a trial registrations policy as one solution to publication bias. The value of trial registries (TRs) has been well established and is supported by funding and government agencies. Yet there is little focus on the type and completeness of data in existing TRs. Objective: Our objectives were to, i) determine the type of data recorded in TRs, ii) assess their quality, iii) compare structure and content of different TRs, and iv) to identify optimal data structures for them. Design: In January 2005, a random sample of trial records was extracted from three international TRs ClinicalTrials.gov, NCI's PDQ Database and ISRCTN Register. No restrictions were placed on trial status, design or medical area, although some TRs adopted inclusion criteria. Records were assessed using a quality checklist consisting of 30 desirable items grouped into five categories, identifying information, trial details, funding, contact details and data collection forms. Results: A pilot study assessing 45 records (15 from each register) was undertaken. The overall quality was poor (median: 16 range: 10-22 items completed per record) and varied considerably across TRs. ClinicalTrial.gov (median 17) and NCIPDQ (median 18) faired better than ISRTCN (median 13) (ClinicalTrial.gov vs. NCIPDQ p=0.79; ClinicalTrial.gov vs. ISRTCN p<0.001; NCIPDQ vs. ISRTCN p<0.001). Records fell short of providing complete data in the category of trial details (items: primary outcome; key trial dates) and contact details (items: full address; fax). A copy of the study data collection form was not included in any record. Results from the definitive study will be available for presentation. Conclusions: Although our quality criteria were not stringent, the preliminary results show considerable variation in the data available in current TRs and an unsatisfactory quality of desirable requirements for trial protocols. The results suggest that there is room for standardization of the type of data recorded in TRs to provide better and more complete essential public information

Compliance of clinical trial registries with the World Health Organization minimum data set : a survey

The original publication is available at http://www.trialsjournal.com/content/10/1/56Background: Since September 2005 the International Committee of Medical Journal Editors has required that trials be registered in accordance with the World Health Organization (WHO) minimum dataset, in order to be considered for publication. The objective is to evaluate registries' and individual trial records' compliance with the 2006 version of the WHO minimum data set. Methods: A retrospective evaluation of 21 online clinical trial registries (international, national, specialty, pharmaceutical industry and local) from April 2005 to February 2007 and a cross-sectional evaluation of a stratified random sample of 610 trial records from the 21 registries. Results: Among 11 registries that provided guidelines for registration, the median compliance with the WHO criteria were 14 out of 20 items (range 6 to 20). In the period April 2005–February 2007, six registries increased their compliance by six data items, on average. None of the local registry websites published guidelines on the trial data items required for registration. Slightly more than half (330/610; 54.1%, 95% CI 50.1% – 58.1%) of trial records completed the contact details criteria while 29.7% (181/610, 95% CI 26.1% – 33.5%) completed the key clinical and methodological data fields. Conclusion: While the launch of the WHO minimum data set seemed to positively influence registries with better standardisation of approaches, individual registry entries are largely incomplete. Initiatives to ensure quality assurance of registries and trial data should be encouraged. Peer reviewers and editors should scrutinise clinical trial registration records to ensure consistency with WHO's core content requirements when considering trial-related publications.Publishers' versio