Publication and non-publication of clinical trials: longitudinal study of applications submitted to a research ethics committee

BACKGROUND: Not all clinical trials are published, which may distort the evidence that is available in the literature. We studied the publication rate of a cohort of clinical trials and identified factors associated with publication and nonpublication of results. METHODS: We analysed the protocols of randomized clinical trials of drug interventions submitted to the research ethics committee of University Hospital (Inselspital) Bern, Switzerland from 1988 to 1998. We identified full articles published up to 2006 by searching the Cochrane CENTRAL database (issue 02/2006) and by contacting investigators. We analyzed factors associated with the publication of trials using descriptive statistics and logistic regression models. RESULTS: 451 study protocols and 375 corresponding articles were analyzed. 233 protocols resulted in at least one publication, a publication rate of 52%. A total of 366 (81%) trials were commercially funded, 47 (10%) had non-commercial funding. 346 trials (77%) were multi-centre studies and 272 of these (79%) were international collaborations. In the adjusted logistic regression model non-commercial funding (Odds Ratio [OR] 2.42, 95% CI 1.14-5.17), multi-centre status (OR 2.09, 95% CI 1.03-4.24), international collaboration (OR 1.87, 95% CI 0.99-3.55) and a sample size above the median of 236 participants (OR 2.04, 95% CI 1.23-3.39) were associated with full publication. CONCLUSIONS: In this cohort of applications to an ethics committee in Switzerland, only about half of clinical drug trials were published. Large multi-centre trials with non-commercial funding were more likely to be published than other trials, but most trials were funded by industry.

Completion and Publication Rates of Randomized Controlled Trials in Surgery: An Empirical Study.

OBJECTIVE: To investigate the prevalence of discontinuation and nonpublication of surgical versus medical randomized controlled trials (RCTs) and to explore risk factors for discontinuation and nonpublication of surgical RCTs. BACKGROUND: Trial discontinuation has significant scientific, ethical, and economic implications. To date, the prevalence of discontinuation of surgical RCTs is unknown. METHODS: All RCT protocols approved between 2000 and 2003 by 6 ethics committees in Canada, Germany, and Switzerland were screened. Baseline characteristics were collected and, if published, full reports retrieved. Risk factors for early discontinuation for slow recruitment and nonpublication were explored using multivariable logistic regression analyses. RESULTS: In total, 863 RCT protocols involving adult patients were identified, 127 in surgery (15%) and 736 in medicine (85%). Surgical trials were discontinued for any reason more often than medical trials [43% vs 27%, risk difference 16% (95% confidence interval [CI]: 5%-26%); P = 0.001] and more often discontinued for slow recruitment [18% vs 11%, risk difference 8% (95% CI: 0.1%-16%); P = 0.020]. The percentage of trials not published as full journal article was similar in surgical and medical trials (44% vs 40%, risk difference 4% (95% CI: -5% to 14%); P = 0.373). Discontinuation of surgical trials was a strong risk factor for nonpublication (odds ratio = 4.18, 95% CI: 1.45-12.06; P = 0.008). CONCLUSIONS: Discontinuation and nonpublication rates were substantial in surgical RCTs and trial discontinuation was strongly associated with nonpublication. These findings need to be taken into account when interpreting surgical literature. Surgical trialists should consider feasibility studies before embarking on full-scale trials.

Planning and reporting of quality-of-life outcomes in cancer trials.

BACKGROUND Information about the impact of cancer treatments on patients' quality of life (QoL) is of paramount importance to patients and treating oncologists. Cancer trials that do not specify QoL as an outcome or fail to report collected QoL data, omit crucial information for decision making. To estimate the magnitude of these problems, we investigated how frequently QoL outcomes were specified in protocols of cancer trials and subsequently reported. DESIGN Retrospective cohort study of RCT protocols approved by six research ethics committees in Switzerland, Germany, and Canada between 2000 and 2003. We compared protocols to corresponding publications, which were identified through literature searches and investigator surveys. RESULTS Of the 173 cancer trials, 90 (52%) specified QoL outcomes in their protocol, 2 (1%) as primary and 88 (51%) as secondary outcome. Of the 173 trials, 35 (20%) reported QoL outcomes in a corresponding publication (4 modified from the protocol), 18 (10%) were published but failed to report QoL outcomes in the primary or a secondary publication, and 37 (21%) were not published at all. Of the 83 (48%) trials that did not specify QoL outcomes in their protocol, none subsequently reported QoL outcomes. Failure to report pre-specified QoL outcomes was not associated with industry sponsorship (versus non-industry), sample size, and multicentre (versus single centre) status but possibly with trial discontinuation. CONCLUSIONS About half of cancer trials specified QoL outcomes in their protocols. However, only 20% reported any QoL data in associated publications. Highly relevant information for decision making is often unavailable to patients, oncologists, and health policymakers.

Modeling of red blood cell life-spans in hematologically normal populations

Despite the impact of red blood cell (RBC) Life-spans in some disease areas such as diabetes or anemia of chronic kidney disease, there is no consensus on how to quantitatively best describe the process. Several models have been proposed to explain the elimination process of RBCs: random destruction process, homogeneous life-span model, or a series of 4-transit compartment model. The aim of this work was to explore the different models that have been proposed in literature, and modifications to those. The impact of choosing the right model on future outcomes prediction--in the above mentioned areas--was also investigated. Both data from indirect (clinical data) and direct life-span measurement (biotin-labeled data) methods were analyzed using non-linear mixed effects models. Analysis showed that: (1) predictions from non-steady state data will depend on the RBC model chosen; (2) the transit compartment model, which considers variation in life-span in the RBC population, better describes RBC survival data than the random destruction or homogenous life-span models; and (3) the additional incorporation of random destruction patterns, although improving the description of the RBC survival data, does not appear to provide a marked improvement when describing clinical data.

Coronary bypass surgery in patients treated with clopidogrel. Is it safe?

PURPOSE OF REVIEW: Current guidelines for the management of acute coronary syndrome clearly recommend that clopidogrel should be started before diagnostic coronary angiography. If patients undergo coronary artery bypass grafting (CABG) early after clopidogrel loading or during continued exposure, it seems reasonable to expect an increase in bleeding complications. RECENT FINDINGS: Earlier studies may have overestimated the risk of bleeding in patient undergoing CABG with prior clopidogrel exposure (5-10-fold increase). Some conflicting results are reported in literature. As reexploration because of excessive bleeding is concerned, a two to three-fold increase must be expected, which is demonstrated in actual trials properly matched to confounding factors. Discontinuation of clopidogrel for 5-7 days prior to urgent CABG as recommended by guidelines is not well adopted in clinical practice for several reasons. SUMMARY: There is a moderately elevated risk of bleeding complications after CABG due to prior clopidogrel exposure alone. However, in clinical practice this risk is added often to patients who carry already elevated surgical risks (urgent procedures, worse coronary anatomy, history of previous myocardial infarction and prior percutaneous intervention), and after bleeding complications singular patients may suffer from consecutive adverse outcome. Cessation of clopidogrel in patients before CABG clearly prolongs hospitalization time and has an estimated 1% risk of coronary events during the waiting period. Risk and benefit have to be balanced in every individual case.

Altern in Würde. Das Konzept der Würde im vierten Lebensalter

Die Verwandlung von der weitgehend souveränen, selbstbestimmten und selbständigen Person zum intensiv abhängigen und sterbenden Menschen wird in der gerontologischen Kategorie des 'vierten Lebensalters' als lebensweltlich und biographisch integrierter Prozess verdeutlicht, der eigene Herausforderungen der Bewältigung bereithält. Die Notwendigkeit der normativen Reflexion dieses Prozesses zeigt sich besonders deutlich an der Problematik eines Würdeverständnisses, das in der Regel unhinterfragt mit den Vorstellungen von Selbstbestimmung und Souveränität verbunden oder gleichgesetzt wird. Der im interdisziplinären Gespräch zwischen Pflege, Medizin und Ethik angelegte Band fragt aus der Perspektive des 'vierten Lebensalters' nach den Konnotationen und Deutungen der Würdekategorie und damit nach den Voraussetzungen, Zielen und Orientierungsmassstäben für den Umgang mit Menschen und notwendige Entscheidungen in dieser Lebensphase, nach dem Konzept einer 'Würde im vierten Lebensalter', das im Kontext von Medizin- und Pflegeethik anwendbar ist.

Sudden death in a case of sickle cell anemia: post-mortem computed tomography and autopsy correlation from a radiologist's perspective

Sickle cell anemia (SCA) is a hemolytic disease characterized by the production of abnormal hemoglobin chains and distorted red blood cell morphology or sickling. "Sickle cell crisis" includes vaso-occlusive crisis, a plastic crisis, sequestration crisis, haemolytic crisis and often culminating in serious complications, organ damage and even sudden death. Post-mortem computed tomography (PMCT) findings of sickle cell disease have never been reported in literature. This case of sudden death from acute hemolytic crisis in SCA where post-mortem computed tomography (PMCT) and autopsy findings complemented each other, both revealing findings invisible to the other and both crucial to the case.

Psychological adaptation to spousal loss in old age: The role of personality

Spousal loss is an inevitable critical life event for most individuals in old age, mostly associated with a negative impact on various well-being measures, ie. lower life satisfaction, higher rates of loneliness and depressive symptoms compared to married peers. While the negative effects on well-being are well documented in literature, the modifying factors accounting for the large variability in adaptation to loss are discussed controversially. The potential relevance of personality in the adaptation process has rarely been examined and findings regarding the role of time since loss are contradictory. Based on a vulnerability-stress-model this contribution aims a) to compare psychological well-being of bereaved individuals with married counterparts and b) to investigate the protective effects of different personality traits (Big Five, resilience), and the role of time since loss for adaptation in terms of life satisfaction, loneliness and depression. Data from a questionnaire study about the loss of a spouse in middle and old age in the German- and French-speaking parts of Switzerland are reported. The study is part of the Swiss National Centre of Competence in Research LIVES (Swiss National Science Foundation). The sample consists of 351 widowed persons (39% men, widowed since 0 - 5 years), and 605 married controls (50% men), aged 60 - 89 years. Group comparisons reveal the detrimental effect of spousal bereavement on all indicators of psychological adaptation. Results from hierarchical regression analyses show furthermore, that the effect of spousal loss on all psychological outcomes is moderated by personality traits. Separate analyses with the group of bereaved individuals suggest, that the protective effect of personality varies by the time passed since loss. Our results contribute to a better understanding of the variability in psychological adaptation to spousal loss in old age and give hints for counselling practice.