Patient-reported conformity of informed consent procedures and participation in clinical research

Background: There is growing evidence that the quality of informed consent in clinical research is often sub-optimal. Aims: To explore the conformity of patient recruitment with recommended informed consent procedures among patients who were invited to participate in a clinical study at a general teaching hospital, and to examine the association between consent procedures and the patients' decision to participate. Design and Methods: All inpatients discharged during a 1-month period were invited to complete a mailed survey in which they reported whether they were invited to participate in a study and whether 13 recommended elements of informed consent actually occurred. Results: Among 1303 respondents, 265 (20.3%) reported that they had been invited to participate in a study, and 191 (72.1%) accepted. While the majority of potential participants were fully informed about practical issues related to the study (e.g. what their participation would consist in), <50% were informed of possible risks or benefits, and only 20% about the origin of the study funds. Only 60% reported satisfactory answers to items assessing the overall information process (e.g. explanations were easy to understand). Older and sicker patients reported lower levels of conformity with informed consent procedures, as did patients who refused to participate in a study. Conclusions: Our results confirm that informed consent procedures fail to meet standards for many patients. In particular, consent information should be adapted to the needs of older and sicker patients. Improving the quality of informed consent may increase patients' participation in clinical researc

Measuring human-error probabilities in drug preparation: a pilot simulation study

Objectives: Designing a safe medication process requires the ability to model its reliability using methods such as probabilistic risk assessment (PRA). However, lack of data, especially on human-error probabilities (HEPs), limits its use. To assess whether small-scale simulations could help generate HEP data, a pilot study was conducted among nurses and anaesthetists. It focused on two core activities, namely, the manual preparation of medications and the arithmetic necessary to prepare drugs. Its specific objectives were to evaluate whether HEPs could be high enough to be measurable and to determine whether these HEPs could be sensitive to individuals and task details. These would give some insight into the level of detail required by PRA analysis. Methods: Thirty nurse and 28 anaesthetist volunteers were involved in the experiment. Nurses and anaesthetists had to prepare medications for 20 patients and 22 syringes of various drugs, respectively. Both groups had to perform 22 calculations relating to the preparation of drugs. HEPs, distribution of HEPs and dependency of HEPs on individuals and task details were assessed. Results: In the preparation tasks, overall HEP was 3.0% for nurses and 6.5% for anaesthetists. In the arithmetic tasks, overall HEP was 23.8% for nurses and 8.9% for anaesthetists. A statistically significant difference was noted between the two groups. In both preparation and arithmetic tasks, HEPs were dependent on individual nurses but not on individual anaesthetists. In every instance, HEPs were dependent on task details. Conclusion: Our study illustrates that small-scale simulations represent an interesting way of generating HEPs. HEPs are, indeed, in the range of 10−2 and 10−1. But in most cases, HEPs depend heavily on operators and task details. This dependency means that the influence of these parameters must be determined before advanced PRA analysis. There is therefore an urgent need to develop experimental research into assessing this influence by means of randomised controlled trial

COOP Charts in French: translation and preliminary data on instrument properties

This paper describes the procedure used to translate the COOP Charts into French and provides preliminary information on the instrument's acceptability, reliability and validity. The charts were translated in several steps: seven initial translations were combined into a first pilot version, which was then tested for acceptability, clarity and alternate wordings in two convenience samples taken from the general population (n=53). The modified version was then reviewed by a lay panel and another translator and submitted by mail to 209 congress participants to test several construct validity hypotheses through known-groups comparisons. A panel of public health professionals discussed the content validity of the charts. Finally, test-retest reliability and concurrent validity with SF-36 Health Survey scores were examined among 65 patients with end-stage renal disease. The translation process identified a wide variability in translation options for several items. The acceptability of the charts was excellent. The test-retest correlations ranged from 0.60 to 0.87. Content validity appeared to be appropriate, except for the chart on ‘social support', which combines the questions of need and availability of social support. The utility of illustrations was questioned by some respondents: many claimed not to have used the illustrations in selecting their response, while others found them to be not expressive enough. Most preliminary tests of construct validity were consistent with theory. This French translation of the COOP Charts appears to be ready for more extensive testing in the intended target population of ambulatory patient

Satisfaction of patients on chronic haemodialysis and peritoneal dialysis

BACKGROUND: In contrast to quality of life, patient satisfaction on chronic haemodialysis (HD) and peritoneal dialysis (PD) has only rarely been studied. PATIENTS AND METHODS: All chronic HD and PD patients of the 19 centres located in western Switzerland were asked to complete a specific questionnaire, assessing dialysis centre characteristics, treatment modalities, and information received before and during dialysis treatment. Comparison between satisfaction with PD and HD was carried out on the patients in the nine centres offering both treatment modalities. RESULTS: Of the 558 questionnaires distributed to chronic HD patients, 455 were returned (response rate 82%). Fifty of 64 PD patients (78%) returned the questionnaire. The two groups were similar in age, gender, and duration of dialysis treatment. Completion rates were &gt;90% for a majority of questions, with the lowest rate for information on sexuality (49% in HD and 54% in PD respectively). The lowest scores were recorded for information received about complications and costs of dialysis, and impact of end-stage kidney disease on sexuality. Satisfaction was lower in anonymous questionnaires. Satisfaction of PD patients was significantly better in 50% of the questions, particularly session tolerance (p&lt;0.001), information about dialysis sessions (p=0.007), and complications (p=0.006). CONCLUSIONS: PD patients were on average more satisfied with their treatment than HD patients. Satisfaction could be improved with more information about potential adverse treatment effects

Use of Treponema pallidum PCR in Testing of Ulcers for Diagnosis of Primary Syphilis(1.).

Treponema pallidum PCR (Tp-PCR) has been noted as a valid method for diagnosing syphilis. We compared Tp-PCR to a combination of darkfield microscopy (DFM), the reference method, and serologic testing in a cohort of 273 patients from France and Switzerland and found the diagnostic accuracy of Tp-PCR was higher than that for DFM

Evaluating predictive pharmacogenetic signatures of adverse events in colorectal cancer patients treated with fluoropyrimidines

The potential clinical utility of genetic markers associated with response to fluoropyrimidine treatment in colorectal cancer patients remains controversial despite extensive study. Our aim was to test the clinical validity of both novel and previously identified markers of adverse events in a broad clinical setting. We have conducted an observational pharmacogenetic study of early adverse events in a cohort study of 254 colorectal cancer patients treated with 5-fluorouracil or capecitabine. Sixteen variants of nine key folate (pharmacodynamic) and drug metabolising (pharmacokinetic) enzymes have been analysed as individual markers and/or signatures of markers. We found a significant association between TYMP S471L (rs11479) and early dose modifications and/or severe adverse events (adjusted OR = 2.02 [1.03; 4.00], p = 0.042, adjusted OR = 2.70 [1.23; 5.92], p = 0.01 respectively). There was also a significant association between these phenotypes and a signature of DPYD mutations (Adjusted OR = 3.96 [1.17; 13.33], p = 0.03, adjusted OR = 6.76 [1.99; 22.96], p = 0.002 respectively). We did not identify any significant associations between the individual candidate pharmacodynamic markers and toxicity. If a predictive test for early adverse events analysed the TYMP and DPYD variants as a signature, the sensitivity would be 45.5 %, with a positive predictive value of just 33.9 % and thus poor clinical validity. Most studies to date have been under-powered to consider multiple pharmacokinetic and pharmacodynamic variants simultaneously but this and similar individualised data sets could be pooled in meta-analyses to resolve uncertainties about the potential clinical utility of these markers

β-Lactam Monotherapy vs β-Lactam-Macrolide Combination Treatment in Moderately Severe Community-Acquired Pneumonia: A Randomized Noninferiority Trial.

IMPORTANCE: The clinical benefit of adding a macrolide to a β-lactam for empirical treatment of moderately severe community-acquired pneumonia remains controversial. OBJECTIVE: To test noninferiority of a β-lactam alone compared with a β-lactam and macrolide combination in moderately severe community-acquired pneumonia. DESIGN, SETTING, AND PARTICIPANTS: Open-label, multicenter, noninferiority, randomized trial conducted from January 13, 2009, through January 31, 2013, in 580 immunocompetent adult patients hospitalized in 6 acute care hospitals in Switzerland for moderately severe community-acquired pneumonia. Follow-up extended to 90 days. Outcome assessors were masked to treatment allocation. INTERVENTIONS: Patients were treated with a β-lactam and a macrolide (combination arm) or with a β-lactam alone (monotherapy arm). Legionella pneumophila infection was systematically searched and treated by addition of a macrolide to the monotherapy arm. MAIN OUTCOMES AND MEASURES: Proportion of patients not reaching clinical stability (heart rate &lt;100/min, systolic blood pressure &gt;90 mm Hg, temperature &lt;38.0°C, respiratory rate &lt;24/min, and oxygen saturation &gt;90% on room air) at day 7. RESULTS: After 7 days of treatment, 120 of 291 patients (41.2%) in the monotherapy arm vs 97 of 289 (33.6%) in the combination arm had not reached clinical stability (7.6% difference, P = .07). The upper limit of the 1-sided 90% CI was 13.0%, exceeding the predefined noninferiority boundary of 8%. Patients infected with atypical pathogens (hazard ratio [HR], 0.33; 95% CI, 0.13-0.85) or with Pneumonia Severity Index (PSI) category IV pneumonia (HR, 0.81; 95% CI, 0.59-1.10) were less likely to reach clinical stability with monotherapy, whereas patients not infected with atypical pathogens (HR, 0.99; 95% CI, 0.80-1.22) or with PSI category I to III pneumonia (HR, 1.06; 95% CI, 0.82-1.36) had equivalent outcomes in the 2 arms. There were more 30-day readmissions in the monotherapy arm (7.9% vs 3.1%, P = .01). Mortality, intensive care unit admission, complications, length of stay, and recurrence of pneumonia within 90 days did not differ between the 2 arms. CONCLUSIONS AND RELEVANCE: We did not find noninferiority of β-lactam monotherapy in patients hospitalized for moderately severe community-acquired pneumonia. Patients infected with atypical pathogens or with PSI category IV pneumonia had delayed clinical stability with monotherapy. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00818610

Does publication bias inflate the apparent efficacy of psychological treatment for major depressive disorder? A systematic review and meta-analysis of US national institutes of health-funded trials

Background The efficacy of antidepressant medication has been shown empirically to be overestimated due to publication bias, but this has only been inferred statistically with regard to psychological treatment for depression. We assessed directly the extent of study publication bias in trials examining the efficacy of psychological treatment for depression. Methods and Findings We identified US National Institutes of Health grants awarded to fund randomized clinical trials comparing psychological treatment to control conditions or other treatments in patients diagnosed with major depressive disorder for the period 1972–2008, and we determined whether those grants led to publications. For studies that were not published, data were requested from investigators and included in the meta-analyses. Thirteen (23.6%) of the 55 funded grants that began trials did not result in publications, and two others never started. Among comparisons to control conditions, adding unpublished studies (Hedges’ g = 0.20; CI95% -0.11~0.51; k = 6) to published studies (g = 0.52; 0.37~0.68; k = 20) reduced the psychotherapy effect size point estimate (g = 0.39; 0.08~0.70) by 25%. Moreover, these findings may overestimate the "true" effect of psychological treatment for depression as outcome reporting bias could not be examined quantitatively. Conclusion The efficacy of psychological interventions for depression has been overestimated in the published literature, just as it has been for pharmacotherapy. Both are efficacious but not to the extent that the published literature would suggest. Funding agencies and journals should archive both original protocols and raw data from treatment trials to allow the detection and correction of outcome reporting bias. Clinicians, guidelines developers, and decision makers should be aware that the published literature overestimates the effects of the predominant treatments for depression