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Improving access to the international coverage of reports of controlled trials in electronic databases: a search of the Australasian Medical Index.

INTRODUCTION: Locating reports of trials from journals not indexed in the major databases presents difficulties to systematic reviewers, and may be a factor in improving the reliability of the reviews. OBJECTIVES: To identify and make available reports of controlled trials from the Australasian Medical Index (AMI). To measure the quality of indexing of trials in AMI. METHODS: Using a highly sensitive search strategy consisting of methodology indexing and free-text terms, records from AMI were read for reports of controlled trials. Trials meeting the criteria were submitted for inclusion in The Cochrane Controlled Trials Register (CCTR) and assessed for the quality of their indexing. RESULTS: 3621 records were downloaded, of which 512 were identified as reports of controlled trials (317 RCTs; 195 CCTs) and submitted to CCTR. The precision of methodology indexing terms was 60%, but sensitivity just 18%. The quality of indexing of trials was generally poor with only 50 tagged with the RCT/CCT publication type term. 453 reports (88%) were not previously available in CCTR. CONCLUSIONS: The large proportion of trials found to be unique to the AMI database increases the pool of studies available to systematic reviewers, and helps ensure CCTR remains the most comprehensive source of trials.

Abstracting and Indexing↗

Are we doing any good by doing really well? (Where's the Bacon?).

Francis Bacon, who with Rene Decartes laid the intellectual foundations for Western science in the seventeenth century, asserted that the purpose of all knowledge is "action in the production of works for ... the relief of man's estate." We assess briefly several aspects of a few of the current efforts directed to the production of such "works" with respect to such "relief" as they may provide: cancer mortality, the medical literature, evidence-based medicine, clinical trials, observational databases and criteria for the promotion and tenure of the medical faculty. We suggest why each of these efforts appears to have failed to some degree and then propose some measures that may possibly serve as correctives.

Clinical Trials as Topic↗

Database studies in asthma pharmacoeconomics: uses, limitations and quality markers.

Asthma is a common chronic disease resulting in significant morbidity and health resource utilisation, and multiple therapeutic options exist. Clinicians and healthcare providers need accurate information on the clinical and cost- effectiveness of asthma treatments to make informed decisions on management strategies. Randomised, controlled trials demonstrate cause and effect relationships between treatments and outcomes, but their tight entry criteria and strict study protocols mean that their results cannot automatically be generalised or used for economic modelling. There is a need for observational data to examine the effectiveness of alternative interventions in routine practice. Clinical and administrative databases are a possible information source for observational studies, and are increasingly used in asthma clinical, epidemiological and economic research. This paper examines the types of database used, the advantages and limitations of such studies and considers quality markers. High quality database studies can provide important epidemiological and economic information that can be of value in understanding the causes and effective management of asthma.

Anti-Asthmatic Agents↗

The role of radiation therapy in malignant pleural mesothelioma: a systematic review.

INTRODUCTION: Radiation therapy may offer patients presenting with malignant pleural mesothelioma (MPM) symptom palliation and improvements in quality of life. This systematic review will address the role of radiation therapy in the management of MPM. METHODS: A thorough systematic search of the literature was conducted for published articles and conference proceedings for applicable abstracts. Relevant trials were selected and assessed. RESULTS: Three small randomized controlled trials compared prophylactic external beam radiation therapy to no radiation therapy for patients with thoracic tracts caused by drainage tubes or diagnostic procedures. None of those trials reported any serious adverse effects. A pooled analysis found no significant reduction in the frequency of procedure tract metastases. Four non-comparative studies have shown that hemithoracic irradiation alone resulted in significant toxicity, including radiation-induced pulmonary fibrosis, radiation pneumonitis, and bronchopleural fistula, without any survival benefit. Few of the identified studies reported on symptom control, and no studies included formal measures of quality of life. CONCLUSION: There is limited evidence for the role of radiotherapy in the management of patients with MPM. Future studies including radiotherapy for the treatment of such patients should include formal measures of quality of life and symptom control.

Clinical Trials as Topic↗

Availability and characterization of transgenic and knockout mice with behavioral manifestations: where to look and what to search for.

Mice altered by transgenesis or gene targeting ("knockouts") have increasingly been employed as alternative effective tools in elucidating the genetic basis of neurophysiology and behavior. Standardization of specific behavioral paradigms and phenotyping strategies will ensure that these behavioral mouse mutants offer robust models for evaluating the efficacy of novel therapeutics in the treatment of hereditary neurological disorders. The Induced Mutant Resource (IMR) at The Jackson Laboratory (Bar Harbor, Maine, USA) imports, cryopreserves, develops, maintains, and distributes to the research community biomedically valuable stocks of transgenic and targeted mutant mice. Information on behavioral and neurological strains-including a phenotypic synopsis, husbandry requirements, strain availability, and genetic typing protocols-is available through the IMR database (http://www.jax.org/resources/documents/imr/). A current catalog of available strains is readily accessible via the JAX Mice Web site at http://jaxmice.jax.org/index.shtml. In addition, The Jackson Laboratory is now home to TBASE (http://tbase.jax.org/), a comprehensive, community database whose primary focus is on mouse knockouts. TBASE accommodates an exhaustive bibliographical resource for transgenic and knockout mice and provides a detailed phenotypic characterization of numerous behavioral knockouts that is primarily extracted from the literature. Concerted efforts to merge the two resources into a new, schematically reformed database are underway.

Animals↗

[Evidence based treatment of epilepsy].

OBJECTIVE: Evidence based medicine is becoming popular in all fields of medicine. Through systematic reviews, critical evaluation, and statistical strategies such as meta analysis it aids to take decisions in clinical practice. We revise the information on the treatment of epilepsy found in the main sources of evidence based medicine. DEVELOPMENT: After commenting some basic concepts such as systematic review, meta analysis, odds ratio, relative risk and numbers needed to treat, we describe the main primary, secondary and tertiary drug information sources with emphasis on sources of evidence based medicine. Some representative examples are given about the information on treatment of epilepsy found in the main sources of evidence based medicine such as TRIP, DARE, Cochrane Library, clinical practice guidelines, Clinical Evidence or Bandolier. Most clinical trials analyze the efficacy and tolerability of add on new antiepileptic drugs in partial refractory epilepsy. However, we found few trials on efficacy and tolerability of these drugs in monotherapy, in newly diagnosed partial epilepsy, on other types of epilepsy or in children. There are also few trials comparing the new antiepileptic drugs between them or in relation to the old ones. CONCLUSION: Treatment of epilepsy is yet an art more than a science because clinical practice decisions depends on therapeutic habits and clinical expertise more than on the results emerging from randomized and controlled clinical trials. Large comparative trials are needed but relevant criteria of efficacy and validated procedures to evaluate quality of life, tolerability or cognitive function outcomes should be used in these trials.

Anticonvulsants↗

Summary of combined clinical analysis of controlled clinical trials with tizanidine.

Data from three placebo-controlled and 11 active-controlled studies of tizanidine were combined to permit analysis of the subsets, which were too small to evaluate within the individual studies. Overall analysis of placebo-controlled data confirms the effectiveness of tizanidine in reducing muscle tone in patients with spasticity of spinal cord origin. Subset analyses suggest that patients with more severe spasticity are more likely to respond, but age, sex, and race were not predictive of response. Comparisons of tizanidine with active controls showed no differences in efficacy compared with baclofen or diazepam. However, when compared with controls, patients treated with tizanidine did not experience increased weakness. Furthermore, patients tolerated tizanidine better than the control medications. More patients experienced adverse events during tizanidine treatment than did patients receiving placebo. The most common adverse events reported were dry mouth, somnolence, asthenia, and dizziness. Mild elevations in liver function tests were noted occasionally, but improved in all patients with dose reduction or withdrawal. Three patients from the double-blind database reported formed visual hallucinations. All three cleared; two continued tizanidine, and one discontinued.

Adult↗

The relational database model and multiple multicenter clinical trials.

The Southwest Oncology Group (SWOG) chose to use a relational database management system (RDBMS) for the management of data from multiple clinical trials because of the underlying relational model's inherent flexibility and the natural way multiple entity types (patients, studies, and participants) can be accommodated. The tradeoffs to using the relational model as compared to using the hierarchical model include added computing cycles due to deferred data linkages and added procedural complexity due to the necessity of implementing protections against referential integrity violations. The SWOG uses its RDBMS as a platform on which to build data operations software. This data operations software, which is written in a compiled computer language, allows multiple users to simultaneously update the database and is interactive with respect to the detection of conditions requiring action and the presentation of options for dealing with those conditions. The relational model facilitates the development and maintenance of data operations software.

Clinical Trials as Topic↗

A review of the accuracy of references in the journal Emergency Medicine.

OBJECTIVE: To assess the accuracy of references in articles published in Emergency Medicine, and to categorize these errors. METHODS: All the references in Volume 12 of Emergency Medicine were listed and numbered consecutively. A sample of 100 references was then selected. Each reference was then checked, initially on an electronic database, with the original article being used as the gold standard. RESULTS: 1469 citations were included in the study. A random sample of 100 was taken and examined in detail. 35 papers were shown to have at least one error, and a total of 41 errors were found. The maximum number of errors in one paper was 3. These errors are analysed in detail. CONCLUSION: Poor reference accuracy is a common problem in medical literature, and Emergency Medicine is not immune to these failings. Authors need to take more care to ensure that the accuracy of citations improves.

Bibliographies as Topic↗

[Interventions to improve the management of diabetes mellitus in primary health care and outpatient community settings].

UNLABELLED: This review should be cited as: Renders CM, Valk GD, Griffin S. Wagner EH, Eijk JThM van, Assendelft WJJ. Interventions to improve the management of diabetes mellitus in primary care, outpatient and community settings (Cochrane Review). In: The Cochrane Library, Issue 2, 2001. Oxford: Update Software. A substantive amendment to this systematic review was last made on 29 June 2000. Cochrane reviews are regularly checked and updated if necessary. BACKGROUND: Diabetes is a common chronic disease that is increasingly managed in primary care. Different systems have been proposed to manage diabetes care. OBJECTIVES: To assess the effects of different interventions, targeted at health professionals or the structure in which they deliver care, on the management of patients with diabetes in primary care, outpatient and community settings. SEARCH STRATEGY: We searched the Cochrane Effective Practice and Organisation of Care Group specialised register, the Cochrane Controlled Trials Register (Issue 4 1999), MEDLINE (1966-1999), EMBASE (1980-1999), Cinahl (1982-1999), and reference lists of articles. SELECTION CRITERIA: Randomised trials (RCTs), controlled clinical trials (CCTs), controlled before and after studies (CBAs) and interrupted time series (ITS) analyses of professional, financial and organisational strategies aimed at improving care for people with Type 1 or Type 2 diabetes. The participants were health care professionals, including physicians, nurses and pharmacists. The outcomes included objectively measured health professional performance or patient outcomes, and self-report measures with known validity and reliability. DATA COLLECTION AND ANALYSIS: Two reviewers independently extracted data and assessed study quality. MAIN RESULTS: Forty-one studies were included involving more than 200 practices and 48,000 patients. Twenty-seven studies were RCTs, 12 were CBAs, and two were ITS. The studies were heterogeneous in terms of interventions, participants, settings and outcomes. The methodological quality of the studies was often poor. In all studies the intervention strategy was multifaceted. In 12 studies the interventions were targeted at health professionals, in nine they were targeted at the organization of care, and 20 studies targeted both. In 15 studies patient education was added to the professional and organisational interventions. A combination of professional interventions improved process outcomes. The effect on patient outcomes remained less clear as these were rarely assessed. Arrangements for follow-up (organisational intervention) also showed a favourable effect on process outcomes. Multiple interventions in which patient education was added or in which the role of the nurse was enhanced also reported favourable effects on patients' health outcomes. REVIEWERS' CONCLUSION: Multifaceted professional interventions can enhance the performance of health professionals in managing patients with diabetes. Organisational interventions that improve regular prompted recall and review of patients (central computerised tracking systems or nurses who regularly contact the patient) can also improve diabetes management. The addition of patient-oriented interventions can lead to improved patient health outcomes. Nurses can play an important role in patient-oriented interventions, through patient education or facilitating adherence to treatment.

Community Health Centers↗

Systematic reviews of strategies to prevent motor vehicle injuries.

BACKGROUND: Information on which strategies have been shown to be effective, which are ineffective, and which strategies have been inadequately evaluated is important for both public policy and future research. OBJECTIVE: To provide systematic reviews of the literature on important strategies to prevent motor vehicle injuries. METHODS: The Injury Control Research Centers (ICRCs) funded by the Centers for Disease Control and Prevention identified 9 important motor vehicle injury prevention strategies. A systematic review of the literature in 9 different computerized databases was conducted to identify relevant controlled trials. These were critically reviewed and summarized. RESULTS: A total of 54,078 citations were reviewed; 1,111 met initial screening criteria. The reports for these citations were obtained and critically reviewed by the ICRCs. Standard criteria for inclusion of articles in the review and for evaluating the methodological quality of the articles were applied. Few randomized controlled trials were found; most controlled studies were either comparisons over time and/or across different populations. Nevertheless, these studies were able to be summarized to provide meaningful conclusions about the effectiveness of various interventions to decrease morbidity and mortality from motor vehicle crashes. CONCLUSIONS: A large body of literature on motor vehicle injury interventions exists. The summary of this literature will provide useful information to direct policy and future research efforts.

Accidents, Traffic↗

In search of truth: the role of systematic reviews and meta-analyses for assessing the effectiveness of rehabilitation with oral implants.

BACKGROUND: It is difficult to determine the effectiveness or potential harm of dental therapies. Thus, any tools able to condense reliable scientific information would be of benefit. PURPOSE: To discuss methods for the assessment of the scientific literature and, in particular, of systematic reviews for evaluating the effectiveness of oral implant rehabilitation procedures. MATERIALS AND METHODS: Various study designs and methods to identify scientific evidence are described, discussed, and ranked. Issues on how to critically appraise randomized controlled clinical trials (RCTs) and systematic reviews are presented. RESULTS: Properly conducted RCTs and structured critical systematic reviews are the gold standard of clinical research for assessing whether a therapeutic intervention is effective. In the field of oral implantology, there is an urgent need to implement more RCTs and to summarize their results in systematic reviews. CONCLUSIONS: Searching of the truth requires training and critical skill. Dentists should be trained on how to integrate their clinical experience with evidence-based research and on how to discriminate between clinically useful scientific information and less useful research.

Animals↗

Proposed consensus for definitions and endpoints for clinical trials of acute kidney transplant rejection.

Progress in transplantation therapeutics requires validation from multicenter trials in which enrollment criteria and endpoint definitions have been standardized. A database of acute rejection was established from 19 North American, European, and Australian transplant centers and included parameters on rejection diagnosis and treatment of 50 consecutive rejection episodes from each center. Patient demographics, induction and maintenance immunosuppressive therapies, antirejection agents (drug, dose, duration), clinical signs (decrease in urine volume, presence of fever of > or =38.5 degrees C), serum creatinine concentration (nadir, at rejection, daily during antirejection therapy to 15 days, and days 30, 90, 180, and 365 after rejection date), rejection biopsy findings, morbidity, recurrence of rejection, and renal function at 1 year were recorded for 953 rejection episodes. From these data, three definitions were proposed. Acute rejection was defined as an immunologic process resulting in a serum creatinine increase of > or =0.4 mg/dL, with or without clinical signs, and should include a biopsy confirmation that has been standardized to the Banff criteria. Corticosteroid-resistant rejection was defined as a rejection episode in which a minimum of 250 to 1000 mg of methylprednisolone administered as initial therapy fails to result in stabilization or reduction of the serum creatinine after 3 days of corticosteroid treatment. Successful response to therapy was defined as a serum creatinine level < or =110% of the serum creatinine on the day of the rejection diagnosis and a return of the serum creatinine to or below the rejection creatinine level by 5 days of therapy with maintenance of this response for a minimum of 30 days. The work represented in the Efficacy Endpoints Database provides a step toward improving definitions in clinical trials. Continuity in clinical trial design should lead to improvements in evaluation of outcomes and, thereby have an effect on clinical practice.

Acute Disease↗

GrainGenes 2.0. an improved resource for the small-grains community.

GrainGenes (http://wheat.pw.usda.gov) is an international database for genetic and genomic information about Triticeae species (wheat [Triticum aestivum], barley [Hordeum vulgare], rye [Secale cereale], and their wild relatives) and oat (Avena sativa) and its wild relatives. A major strength of the GrainGenes project is the interaction of the curators with database users in the research community, placing GrainGenes as both a data repository and information hub. The primary intensively curated data classes are genetic and physical maps, probes used for mapping, classical genes, quantitative trait loci, and contact information for Triticeae and oat scientists. Curation of these classes involves important contributions from the GrainGenes community, both as primary data sources and reviewers of published data. Other partially automated data classes include literature references, sequences, and links to other databases. Beyond the GrainGenes database per se, the Web site incorporates other more specific databases, informational topics, and downloadable files. For example, unique BLAST datasets of sequences applicable to Triticeae research include mapped wheat expressed sequence tags, expressed sequence tag-derived simple sequence repeats, and repetitive sequences. In 2004, the GrainGenes project migrated from the AceDB database and separate Web site to an integrated relational database and Internet resource, a major step forward in database delivery. The process of this migration and its impacts on database curation and maintenance are described, and a perspective on how a genomic database can expedite research and crop improvement is provided.

Breeding↗

Clinical safety evaluation of combination vaccines.

The development plan for new combination vaccines should include clinical studies designed to provide an adequate safety database (as well as efficacy data) to support licensure. Ideally, randomized studies to compare the safety of the combination vaccine with the separately administered components (or already licensed combinations of components) should be performed. For new combination vaccines having components with proven efficacy, comparative immunogenicity data may provide a sufficient basis to support efficacy, precluding the need for a large efficacy study. In the absence of the safety database that would have been derived from such an efficacy study, it is important to conduct a comparative safety study with a sample size suitable for the evaluation of less common adverse events. For large safety trials, a simplified design where only a subset of subjects is assessed in detail for the more common adverse events may be appropriate.

Biometry↗

Data validity and integrity checking in clinical trials information systems.

Data validity and integrity checks in clinical trials (CT) databases have special procedures. We describe a new logic-driven system, coupled with a CT information system, which manages data anomalies found in CT databases. Q-GEM identifies data problems, and issues, emails to study sites, and tracks data discrepancy forms until their final resolution.

Clinical Trials as Topic↗

Consensus conferences must include a systematic search and categorization of the evidence.

BACKGROUND: Ideally, a consensus panel combines expert knowledge with external evidence derived from the literature. To date, many consensus conferences do not use a structured approach to search the literature, but simply compile an add-on reference list from all papers cited by the panelists. This study examined how well such panelists retrieved the relevant literature. METHODS: We used the reference lists of nine surgeons who took part in a consensus conference on common bile duct stones. We included all papers that were referred to as randomized controlled trials (RCTs). We then compared this list with a database search in order to calculate sensitivity and specificity. RESULTS: The nine experts cited between 35 and 518 papers, but only eight papers on average were RCTs. Of the 49 papers that the experts believed to be RCTs, only 23 actually were RCTs. The sensitivity resp. specificity for correctly identifying an RCT was 0.21 (95% Cl, 0.11-0.30) resp. 0.80 (95% Cl; 0.64-0.95). RCTs that included the word "randomized" in their title were significantly more likely to be identified (relative risk, 1.31; 95% Cl, 1.18-1.45). CONCLUSION: Our data indicate that consensus panelists usually do not perform systematic literature searches, but simply use their favorite papers to back up their arguments. Because this may lead to a biased selection of the evidence base on which the consensus statements are founded, a systematic search of all relevant articles should become a mandatory task in any consensus or guideline process.

Consensus Statements as Topic↗