Publication bias and meta-analyses: a practical example. Effect of including a clinical example on the ability of physical therapists to apply information in a technical research report. An analysis of the effect of funding source in randomized clinical trials of second generation antipsychotics for the treatment of schizophrenia. Adjacent segment motion after anterior cervical discectomy and fusion versus Prodisc-c cervical total disk arthroplasty: analysis from a randomized, controlled trial. Evidence of improving quality of reporting of randomized controlled trials in subfertility. Association of industry sponsorship to published outcomes in gastrointestinal clinical research. The pilot study of a telephone disease management program for depression. [The response to a specific bronchial provocation test and the evolution of occupational asthma. A longitudinal study in subjects with toluene diisocyanate-induced asthma]. How study design affects outcomes in comparisons of therapy. I: Medical.
Publication bias is widely appreciated, but considerable time and effort are needed to locate and obtain data from unpublished randomized controlled trials (RCTs), those published in non-English language journals or those reported in the gray literature; for this publication, we will call this collection of trials the "gray+literature." However, excluding such trials from systematic reviews could introduce bias and give rise to misleading conclusions.
                We aimed to explore and quantify the impact of inclusion of gray+ literature on the results of all completed individual patient data (IPD) reviews coordinated by our group (13 meta-analyses). For each IPD review, results were calculated for RCTs fully published in English language journals and RCTs fully published in English language journals and the gray+literature.
                The IPD meta-analyses based only on RCTs that were fully published in English language journals tended to give more favorable results than those that included RCTs from the gray+literature. Although in most cases the addition of gray+data gave less encouraging results, moving the estimated treatment effect toward a null result, the direction of effect was not always predictable.
                We recommend that all systematic reviews should at least attempt to identify trials reported in the gray+literature and, where possible, obtain data from them. The purpose of this study was to determine whether an example in a technical research report would affect application of content to hypothetical patient problems and to future patients.
                Subjects were 69 physical therapists who routinely used isokinetic equipment in the treatment of patients with knee joint pathologies.
                Thirty-five subjects (group 1) read a research report that described mathematical models for predicting preinjury quadriceps femoris and hamstring muscle performance. The report included an example of applying the information. The remaining 34 subjects (group 2) read the same research report with the example omitted. Subjects were asked to select appropriate prediction models and determine preinjury knee torques for two hypothetical patients. Subjects were also contacted 6 to 12 weeks after initial data collection to determine whether they had applied research report results in their treatments of patients.
                Chi-square analyses indicated manuscript type was not related to the selection of correct models, but group 1 subjects computed correct torque values more frequently than did group 2 subjects. Insufficient data were available regarding application of research report content to patients.
                The results indicate application of technically oriented research reports may be enhanced by including examples of applications. (Gross MT, Sekerak DK, Allen DD. Effect of including a clinical example on the ability of physical therapists to apply information in a technical research report. The effect of funding source on the outcome of randomized controlled trials has been investigated in several medical disciplines; however, psychiatry has been largely excluded from such analyses. In this article, randomized controlled trials of second generation antipsychotics in schizophrenia are reviewed and analyzed with respect to funding source (industry vs. non-industry funding).
                A literature search was conducted for randomized, double-blind trials in which at least one of the tested treatments was a second generation antipsychotic. In each study, design quality and study outcome were assessed quantitatively according to rating scales. Mean quality and outcome scores were compared in the industry-funded studies and non-industry-funded studies. An analysis of the primary author's affiliation with industry was similarly performed.
                Results of industry-funded studies significantly favored second generation over first generation antipsychotics when compared to non-industry-funded studies. Non-industry-funded studies showed a trend toward higher quality than industry-funded studies; however, the difference between the two was not significant. Also, within the industry-funded studies, outcomes of trials involving first authors employed by industry sponsors demonstrated a trend toward second generation over first generation antipsychotics to a greater degree than did trials involving first authors employed outside the industry (p=0.05).
                While the retrospective design of the study limits the strength of the findings, the data suggest that industry bias may occur in randomized controlled trials in schizophrenia. There appears to be several sources by which bias may enter clinical research, including trial design, control of data analysis and multiplicity/redundancy of trials. Post hoc analysis of data acquired in a prospective, randomized, controlled trial.
                To compare adjacent segment motion after anterior cervical discectomy and fusion (ACDF) versus cervical total disc arthroplasty (TDA).
                TDA has been designed to be a motion-preserving device, thus theoretically normalizing adjacent segment kinematics. Clinical studies with short-term follow-up have yet to demonstrate a consistent significant difference in the incidence of adjacent segment disease.
                Two hundred nine patients at 13 sites were treated in a prospective, randomized, controlled trial of ACDF versus TDA for single-level symptomatic cervical degenerative disc disease (SCDD). Flexion and extension radiographs were obtained at all follow-up visits. Changes in ROM were compared using the Wilcoxon signed-rank test and the Mann-Whitney U test. Predictors of postoperative ROM were determined by multivariate analysis using mixed effects linear regression.
                Data for 199 patients were available with 24-month follow-up. The groups were similar with respect to baseline demographics. A significant increase in motion at the cranial and caudal adjacent segments after surgery was observed in the ACDF group only (cranial: ACDF: +1.4° (0.4, 2.4), P = 0.01; TDA: +0.8°, (-0.1, +1.7), P = 0.166; caudal: ACDF: +2.6° (1.3, 3.9), P < 0.0001; TDA: +1.3, (-0.2, +2.8), P = 0.359). No significant difference in adjacent segment ROM was observed between ACDF and TDA. Only time was a significant predictor of postoperative ROM at both the cranial and caudal adjacent segments.
                Adjacent segment kinematics may be altered after ACDF and TDA. Multivariate analysis showed time to be a significant predictor of changes in adjacent segment ROM. No association between the treatment chosen (ACDF vs. TDA) and ROM was observed. Furthermore clinical follow-up is needed to determine whether possible differences in adjacent segment motion affect the prevalence of adjacent segment disease in the two groups. The quality of randomized controlled trials (RCTs) in subfertility and their suitability for inclusion in meta-analyses have been assessed in the past and found to be insufficient. Our aim was to assess whether this quality has improved over time, particularly since the publication of the Consolidated Standards of Reporting Trials (CONSORT) statement, and to assess what proportion of trials could be included in the meta-analyses of pregnancy outcomes such as those included in Cochrane Reviews.
                A selection of subfertility trials published in 1990, 1996 and 2002 was collected from the Cochrane Menstrual Disorder and Subfertility Group (MDSG) database. Only trials published in English as full journal articles, claiming to be randomized and reporting on pregnancy outcomes, were included.
                One hundred and sixty-four trials met our inclusion criteria. Twenty-four (15%) were found not to be randomized, despite claims, and only 10 trials (6%) provided adequate details on the methods of randomization and allocation concealment. Of these, only three had sufficient details extractable to allow for an intention-to-treat analysis of the outcome 'live birth'.
                Although an improvement in some subfertility-specific issues was observed, the quality of reporting of RCTs still needs to improve to make them suitable for inclusion in meta-analyses such as those in the Cochrane Library. Recent years have seen an increase in industry sponsorship of clinical trials throughout medicine. We conducted a study to evaluate the association of industry sponsorship to published outcomes in gastrointestinal (GI) clinical research. Our aims were (1) to evaluate the trends in the source of funding for GI clinical research during the period from 1992 to 2002-2003, (2) to determine whether the source of study funding predicted the likelihood that a study would publish results that favor the drug or device being tested, and (3) to determine whether differences exist in the methodologic quality of the investigational study methods used in studies funded by private industry versus other sources.
                We selected all clinical studies evaluating a drug or device from 4 prominent GI journals (Gastroenterology, The American Journal of Gastroenterology, Hepatology, and Gastrointestinal Endoscopy). All studies were abstracted by using a standardized data abstraction form. We evaluated the trends in funding source for studies published during the years 1992, 2002, and 2003. All selected studies were scored for methodologic quality by using a previously validated scoring system. The percentage of studies that reported outcomes that favored the device or drug being tested against the standard therapy or placebo was determined for each funding source. A funnel plot was constructed to assess for the presence of negative publication bias.
                A total of 6326 studies were reviewed. For the 1992 trend data, 1860 studies were reviewed, and 135 were selected for inclusion in the study. Ninety-five studies were studies involving the investigation of drugs, and 40 studies involved the testing of a device. For the 2002-2003 data 4466 studies were reviewed, and 315 were selected for inclusion in the study. Two hundred twenty-two studies were clinical trials involving the investigation of drugs, and 93 were clinical trials involving devices. In comparing 1992 to 2002, the percentage of studies funded by industry sources more than doubled from 10% to greater than 28% of the total studies assessed. There was an associated decline in the proportion of studies with funding from non-industry sources during this period (62% to less than 48%). The percentage of studies that did not disclose a funding source fell modestly from 28% to 24%. We found that 86% of studies funded by private industry reported a result favorable to the study drug or device, and 83% of studies funded by academic sources reported a result favorable to the study drug or device (P=.572). On average, studies funded by private industry had a higher methodology score than studies funded by traditional academic sources (75 of 100 vs 65 of 100; P=.005). Analysis of the funnel plot did not reveal evidence of bias against the publication of small studies with insignificant results.
                The proportion of research funded by industry has more than doubled during the last decade and currently comprises almost half of the funding for GI clinical research. Industry-sponsored studies are, on average, of superior methodologic quality to studies funded by other sources. Industry-sponsored studies in leading GI journals were no more likely than other studies to publish results that favored the study sponsor, although an extremely high percentage of all studies in these journals reported positive results. There has been only a modest decline in studies not acknowledging a funding source. Most depressed patients are seen and treated exclusively by primary care clinicians. However, primary care patients with depression are often not adequately treated. The aims of this pilot study were to measure the impact of a telephone disease management program on patient outcome and clinician adherence to practice guidelines, measure the relationship of clinician adherence to patient outcome, and explore the measurement of patient adherence to clinician recommendations and its impact on patient outcomes. Thirty-five primary care practices in the University of Pennsylvania Health System were randomized to telephone disease management (TDM) or "usual care" (UC). All patients received a baseline and a 16-week follow-up clinical evaluation performed over the telephone. Those from TDM practices also received follow-up contact at least every 3 weeks, with formal evaluations at weeks 6 and 12. These interval contacts were designed to facilitate patient and clinician adherence to a treatment algorithm based on the Agency for Health Research and Quality (AHRQ) practice guidelines. Depressive symptoms evaluated with the Community Epidemiologic Survey of Depression (CES-D) scale as well as guideline adherence were the primary outcome measures. Sixty-one patients were enrolled in this pilot project. The overall effect for CES-D scores over time was significant, (P <.001), indicating that those participating in the trial (both TDM and UC groups) showed significant improvement. The interaction between intervention condition and time was also significant (P <.05), indicating that TDM patients improved significantly more over time than did UC patients. A greater proportion of TDM patients had CES-D scores <16 by Week 16 (66.7 versus 33.3%; chi(2), P <.05). The improvement in depression outcome for the TDM group was related to its impact on improving clinician adherence to depression treatment algorithms. The TDM pilot did not show a statistically significant effect on improving patient adherence to clinician recommendations, however. This preliminary data suggests that TDM for depression improves both clinician guideline adherence and patient outcomes in the acute phase of depression. The effect on patient outcome is at least partially explained by the effect of TDM on clinician adherence to depression treatment algorithms. The aim of this study was to investigate the progression and long-term consequences of occupational asthma and to evaluate the effect of the pattern of response to specific bronchoprovocation test (SBPT) in the prognosis of occupational asthma among 40 subjects with asthma due to toluene diisocyanate (TDI). Nine subjects had immediate asthma, 25 subjects had late asthma and 6 subjects had dual asthma. Respiratory symptoms, persistence of exposure to TDI and lung function have been investigated both at diagnosis and at follow-up examination. At follow-up examination, 70.0% of the subjects were not exposed to TDI, and only 14.3% of "non-exposed" subjects were completely asymptomatic. At follow-up examination, 71.4% of "exposed" subjects and 55.6% of "non-exposed" subjects were regularly treated with medications because of their asthma (no statistical difference). No significant differences have been found in symptoms prevalence or lung function between "exposed" and "non-exposed" subjects. After comparing the results obtained at diagnosis and at follow-up examination, a significant decrease in FVC both in "exposed" and "non-exposed" groups (p < 0.005 and p < 0.0005, respectively) and a significant decrement in FEV1 (p < 0.05) and FVC (p < 0.0005) among the subjects with late asthma, was found. We can conclude that, despite the removal from TDI exposure, occupational asthma can lead to permanent disability with important socio-economic consequences, and late response to SBPT may be a negative prognostic factor in TDI asthma. We analysed 113 reports published in 1980 in a sample of medical journals to relate features of study design to the magnitude of gains attributed to new therapies over old. Overall we rated 87 per cent of new therapies as improvements over standard therapies. The mean gain (measured by the Mann-Whitney statistic) was relatively constant across study designs, except for non-randomized controlled trials with sequential assignment to therapy, which showed a significantly higher likelihood that a patient would do better on the innovation than on standard therapy (p = 0.004). Randomized controlled trials that did not use a double-blind design had a higher likelihood of showing a gain for the innovation than did double-blind trials (p = 0.02). Any evaluation of an innovation may include both bias and the true efficacy of the new therapy, therefore we may consider making adjustments for the average bias associated with a study design. When interpreting an evaluation of a new therapy, readers should consider the impact of the following average adjustments to the Mann-Whitney statistic: for trials with non-random sequential assignment a decrease of 0.15, for non-double-blind randomized controlled trials a decrease of 0.11.
Although there has been a large amount of research in this area, most studies were excluded due to inherent problems in the nature of their crossover designs. Usually data are not reported before the crossover and the nature of TD and its likely response to treatments makes it imprudent to use this data. The review provides little usable information for service users or providers and more well designed and reported studies are indicated.