Objective To estimate the frequency with which results of large randomized clinical trials registered with ClinicalTrials.gov are not available to the public. Design Cross sectional analysisSetting Trials with at least 500 participants that were prospectively registered with ClinicalTrials.gov and completed prior to January 2009. Data sourcesPubMed, Google Scholar, and Embase were searched to identify published manuscripts containing trial results. The final literature search occurred in November 2012. Registry entries for unpublished trials were reviewed to determine whether results for these studies were available in the ClinicalTrials.gov results database. Main outcome measuresThe frequency of non-publication of trial results and, among unpublished studies, the frequency with which results are unavailable in the ClinicalTrials.gov database. ResultsOf 585 registered trials, 171 (29%) remained unpublished. These 171 unpublished trials had an estimated total enrollment of 299 763 study participants. The median time between study completion and the final literature search was 60 months for unpublished trials. Non-publication was more common among trials that received industry funding (150/468, 32%) than those that did not (21/117, 18%), P=0.003. Of the 171 unpublished trials, 133 (78%) had no results available in ClinicalTrials.gov.Conclusions Among this group of large clinical trials, non-publication of results was common and the availability of results in the ClinicalTrials.gov database was limited. A substantial number of study participants were exposed to the risks of trial participation without the societal benefits that accompany the dissemination of trial results. IntroductionRandomized clinical trials are a critical means of advancing medical knowledge. Clinical trials depend on the willingness of participants to expose themselves to the risks of randomization, blinding, and unproven interventions. The ethical justification for these risks is that society will eventually benefit from the knowledge gained from the trial.1 Because the risks involved in trial participation may be significant, and because individual trial participants often do not benefit directly from trial participation, substantial safeguards have been implemented to protect the interests of study participants both prior to and during the trial.2 These safeguards take multiple forms, including oversight by institutional review boards, the informed consent process, and data and safety monitoring boards. Until recently, the protection of the interests of study participants after trial completion has received significantly less emphasis. This began to change in 1997 with the signing of the Food and Drug Administration Modernization Act in the United States, which mandated that the US Department of Health and Human Services establish a registry of clinical trials, thereby providing permanent, public access to information on the conduct of both publicly and privately funded clinical trials. In 2005 the International Committee of Medical...

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Objective To examine inter-relationships among stress due to infant appearance and behavior in the NICU, parental role alteration stress in the NICU, depressive symptoms, state anxiety, post-traumatic stress symptoms, and daily hassles exhibited by African American mothers of preterm infants and to determine whether there were sub-groups of mothers based on patterns of psychological distress. Method 177 African American mothers completed questionnaires on their psychological distress at enrollment during infant hospitalization and 2, 6, 12, 18, and 24 months after term. Results Psychological distress measures were inter-correlated. There were four latent classes of mothers: the low distress class with low scores on all measures; the high NICU-related stress class with high infant appearance and parental role stress and moderate scores on other measures; the high depressive symptoms class with high depressive symptoms and state anxiety and moderately elevated scores on NICU-related stress and post-traumatic stress symptoms; the extreme distress class with the highest means on all measures. Infants in the high stress class were sicker than infants in the other classes. The extreme distress class mothers averaged the lowest educational level. The classes differed on distress measures, worry about the child, and parenting stress through 24 months with the extreme distress class having the highest values. Conclusion Although different types of maternal psychological distress were substantially related, there were distinct sub-groups of mothers that were identifiable in the NICU. Moreover, these sub-groups continued to differ on trajectories of distress and on their perceptions of the infants and parenting through 24 months after term.

In Uganda, community-based health programs using volunteers should focus on strengthening support systems to address transportation and stockout issues and on improving links with the health structure while reinforcing effort recognition, status, and acquisition of new skills.

The value of self-monitoring of blood glucose (SMBG) levels in patients with non-insulin-treated type 2 diabetes has been debated. OBJECTIVE To compare 3 approaches of SMBG for effects on hemoglobin A 1c levels and health-related quality of life (HRQOL) among people with non-insulin-treated type 2 diabetes in primary care practice. DESIGN, SETTING, AND PARTICIPANTS The Monitor Trial study was a pragmatic, open-label randomized trial conducted in 15 primary care practices in central North Carolina. Participants were randomized between January 2014 and July 2015. Eligible patients with type 2 non-insulin-treated diabetes were: older than 30 years, established with a primary care physician at a participating practice, had glycemic control (hemoglobin A 1c) levels higher than 6.5% but lower than 9.5% within the 6 months preceding screening, as obtained from the electronic medical record, and willing to comply with the results of random assignment into a study group. Of the 1032 assessed for eligibility, 450 were randomized. INTERVENTIONS No SMBG, once-daily SMBG, and once-daily SMBG with enhanced patient feedback including automatic tailored messages delivered via the meter. MAIN OUTCOMES AND MEASURES Coprimary outcomes included hemoglobin A 1c levels and HRQOL at 52 weeks. RESULTS A total of 450 patients were randomized and 418 (92.9%) completed the final visit. There were no significant differences in hemoglobin A 1c levels across all 3 groups (P = .74; estimated adjusted mean hemoglobin A 1c difference, SMBG with messaging vs no SMBG, −0.09%; 95% CI, −0.31% to 0.14%; SMBG vs no SMBG, −0.05%; 95% CI, −0.27% to 0.17%). There were also no significant differences found in HRQOL. There were no notable differences in key adverse events including hypoglycemia frequency, health care utilization, or insulin initiation. CONCLUSIONS AND RELEVANCE In patients with non-insulin-treated type 2 diabetes, we observed no clinically or statistically significant differences at 1 year in glycemic control or HRQOL between patients who performed SMBG compared with those who did not perform SMBG. The addition of this type of tailored feedback provided through messaging via a meter did not provide any advantage in glycemic control. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT02033499

Fabienne Shumbusho and colleagues evaluate a task-shifting model of nurse-centered antiretroviral treatment prescribing in rural primary health centers in Rwanda and find that nurses can effectively and safely prescribe ART when given adequate training, mentoring, and support.

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Outcome-dependent sampling (ODS) schemes can be a cost effective way to enhance study efficiency. The case-control design has been widely used in epidemiologic studies. However, when the outcome is measured on a continuous scale, dichotomizing the outcome could lead to a loss of efficiency. Recent epidemiologic studies have used ODS sampling schemes where, in addition to an overall random sample, there are also a number of supplemental samples that are collected based on a continuous outcome variable. We consider a semiparametric empirical likelihood inference procedure in which the underlying distribution of covariates is treated as a nuisance parameter and is left unspecified. The proposed estimator has asymptotic normality properties. The likelihood ratio statistic using the semiparametric empirical likelihood function has Wilks-type properties in that, under the null, it follows a chi-square distribution asymptotically and is independent of the nuisance parameters. Our simulation results indicate that, for data obtained using an ODS design, the semiparametric empirical likelihood estimator is more efficient than conditional likelihood and probability weighted pseudolikelihood estimators and that ODS designs (along with the proposed estimator) can produce more efficient estimates than simple random sample designs of the same size. We apply the proposed method to analyze a data set from the Collaborative Perinatal Project (CPP), an ongoing environmental epidemiologic study, to assess the relationship between maternal polychlorinated biphenyl (PCB) level and children's IQ test performance.