Search

Background: The Targeted Learning roadmap provides a systematic guide for generating and evaluating real-world evidence (RWE). From a regulatory perspective, RWE arises from diverse sources such as randomized controlled trials that make use of real-world data, observational studies, and other study designs. This paper illustrates a principled approach to assessing the validity and interpretability of RWE. Methods: We applied the roadmap to a published observational study of the dose–response association between ritodrine hydrochloride and pulmonary edema among women pregnant with twins in Japan. The goal was to identify barriers to causal effect estimation beyond unmeasured confounding reported by the study's authors, and to explore potential options for overcoming the barriers that robustify results. Results: Following the roadmap raised issues that led us to formulate alternative causal questions that produced more reliable, interpretable RWE. The process revealed a lack of information in the available data to identify a causal dose–response curve. However, under explicit assumptions the effect of treatment with any amount of ritodrine versus none, albeit a less ambitious parameter, can be estimated from data. Conclusions: Before RWE can be used in support of clinical and regulatory decision-making, its quality and reliability must be systematically evaluated. The TL roadmap prescribes how to carry out a thorough, transparent, and realistic assessment of RWE. We recommend this approach be a routine part of any decision-making process. [ABSTRACT FROM AUTHOR]

Background: Complementary and alternative medicine (CAM), such as acupuncture and herbal medicine, is popular in many countries. Yet, treatment outcomes of CAM are found to vary significantly between medical trials in different social environments. This paper addresses how the social organization of medicine affects medical treatment outcomes. In particular, it examines the extent to which two popular complementary and alternative medicine (CAM) interventions (acupuncture and herbal medicine) are coordinated with biomedicine and how coordination characteristics are related to the treatment outcomes of the two CAM interventions. Methods: This paper conducts an archival analysis of the institutional settings of the CAM interventions in Japan and the U.S. It also conducts a systematic content analysis of the treatment outcomes in 246 acupuncture reports and 528 herbal medicine reports that are conducted in Japan or the U.S. and registered in the Cochrane Library's Central Register of Controlled Trials (CENTRAL), and 716 acupuncture reports and 3,485 herbal medicine reports that are from Japan or the U.S. and listed in MEDLINE. It examines the association between the treatment outcomes of the two interventions and the geographical location of the reports; it also explores how the institutional settings of the interventions are related to the treatment outcomes. Results: Japanese herbal medicine is integrated into the national medical system the most and American herbal medicine the least; American acupuncture and Japanese acupuncture fall in the middle. Treatment outcomes are the most favorable for Japanese herbal medicine and the least favorable for American herbal medicine. The outcomes of American acupuncture and Japanese acupuncture fall in the middle. Conclusions: The co-utilization of CAM with biomedicine can produce difficulties due to tensions between CAM and biomedicine. These difficulties and subsequent CAM treatment outcomes vary, depending on how CAM is institutionalized in relation to biomedicine in the national medical system. Coordinated CAM interventions are more likely to be effective and synergic with biomedicine, when compared to uncoordinated ones. [ABSTRACT FROM AUTHOR]

Background: SUN(^_^)D, the Strategic Use of New generation antidepressants for Depression, is an assessor-blinded, parallel-group, multicenter pragmatic mega-trial to examine the optimum treatment strategy for the first- and second-line treatments for unipolar major depressive episodes. The trial has three steps and two randomizations. Step I randomization compares the minimum and the maximum dosing strategy for the first-line antidepressant. Step II randomization compares the continuation, augmentation or switching strategy for the second-line antidepressant treatment. Step III is a naturalistic continuation phase. The original protocol was published in 2011, and we hereby report its updated protocol including the statistical analysis plan.Results: We implemented two important changes to the original protocol. One is about the required sample size, reflecting the smaller number of dropouts than had been expected. Another is in the organization of the primary and secondary outcomes in order to make the report of the main trial results as pertinent and interpretable as possible for clinical practices. Due to the complexity of the trial, we plan to report the main results in two separate reports, and this updated protocol and the statistical analysis plan have laid out respective primary and secondary outcomes and their analyses. We will convene the blind interpretation committee before the randomization code is broken.Conclusion: This paper presents the updated protocol and the detailed statistical analysis plan for the SUN(^_^)D trial in order to avoid reporting bias and data-driven results.Trial Registration: ClinicalTrials.gov: NCT01109693 (registered on 21 April 2010). [ABSTRACT FROM AUTHOR]

Background: Major depression is one of the most debilitating diseases in terms of quality of life. Less than half of patients suffering from depression can achieve remission after adequate antidepressant treatment. Another promising treatment option is cognitive-behavior therapy (CBT). However, the need for experienced therapists and substantive dedicated time prevent CBT from being widely disseminated. In the present study, we aim to examine the effectiveness of switching antidepressants and starting a smartphone-based CBT program at the same time, in comparison to switching antidepressants only, among patients still suffering from depression after adequate antidepressant treatment.Methods/design: A multi-center randomized trial is currently being conducted since September 2014. The smartphone-based CBT program, named the "Kokoro-App," for major depression has been developed and its feasibility has been confirmed in a previous open study. The program consists of an introduction, 6 sessions and an epilogue, and is expected to be completed within 9 weeks by patients. In the present trial, 164 patients with DSM-5 major depressive disorder and still suffering from depressive symptoms after adequate antidepressant treatment for more than 4 weeks will be allocated to the Kokoro-App plus switching antidepressant group or the switching antidepressant alone group. The participants allocated to the latter group will receive full components of the Kokoro-App after 9 weeks. The primary outcome is the change in the total score on the Patient Health Questionnaire through the 9 weeks of the program, as assessed at week 0, 1, 5 and 9 via telephone by blinded raters. The secondary outcomes include the change in the total score of the Beck Depression Inventory-II, change in side effects as assessed by the Frequency, Intensity and Burden of Side Effects Rating, and treatment satisfaction.Discussion: An effective and reachable intervention may not only lead to healthier mental status among depressed patients, but also to reduced social burden from this illness. This paper outlines the background and methods of a trial that evaluates the possible additive value of a smartphone-based CBT program for treatment-resistant depression.Trial Registration: UMIN-CTR: UMIN000013693 (registered on 1 June 2014). [ABSTRACT FROM AUTHOR]