Effect of vitamin D supplementation on total and allergen-specific IgE in children with asthma and low vitamin D levels.

BACKGROUND: Observational studies have yielded inconsistent findings for the relation between vitamin D level and total IgE or allergic sensitization. OBJECTIVE: To determine whether vitamin D supplementation reduces levels of total IgE and IgE to each of 2 common indoor allergens in children with asthma and low vitamin D levels. METHODS: Total IgE, IgE to Dermatophagoides pteronyssinus, and IgE to Blattella germanica were measured at the randomization and exit visits for 174 participants in the Vitamin D Kids Asthma Study, a multicenter, double-blind, randomized placebo-controlled trial of vitamin D3 supplementation (4000 IU/d) to prevent severe exacerbations in children with persistent asthma and vitamin D levels less than 30 ng/mL. Multivariable linear regression was used for the analysis of the effect of vitamin D supplementation on change in each IgE measure. RESULTS: Participants were followed for an average of 316 days. At the exit visit, more subjects in the vitamin D arm achieved a vitamin D level equal to or more than 30 ng/mL compared with those in the placebo arm (87% vs 30%; P < .001). In a multivariable analysis, vitamin D3 supplementation had no significant effect on change in total IgE, IgE to Dermatophagoides pteronyssinus, or IgE to Blattella germanica between the exit and randomization visits (eg, for log10 total IgE, ß = 0.007; 95% CI, -0.061 to 0.074; P = .85). CONCLUSIONS: Vitamin D supplementation, compared with placebo, has no significant effect on serum levels of total IgE, IgE to dust mite, or IgE to cockroach in children with asthma and low vitamin D levels.

Effect of Vitamin D3 Supplementation on Severe Asthma Exacerbations in Children With Asthma and Low Vitamin D Levels: The VDKA Randomized Clinical Trial.

Importance: Severe asthma exacerbations cause significant morbidity and costs. Whether vitamin D3 supplementation reduces severe childhood asthma exacerbations is unclear. Objective: To determine whether vitamin D3 supplementation improves the time to a severe exacerbation in children with asthma and low vitamin D levels. Design, Setting, and Participants: The Vitamin D to Prevent Severe Asthma Exacerbations (VDKA) Study was a randomized, double-blind, placebo-controlled clinical trial of vitamin D3 supplementation to improve the time to severe exacerbations in high-risk children with asthma aged 6 to 16 years taking low-dose inhaled corticosteroids and with serum 25-hydroxyvitamin D levels less than 30 ng/mL. Participants were recruited from 7 US centers. Enrollment started in February 2016, with a goal of 400 participants; the trial was terminated early (March 2019) due to futility, and follow-up ended in September 2019. Interventions: Participants were randomized to vitamin D3, 4000 IU/d (n = 96), or placebo (n = 96) for 48 weeks and maintained with fluticasone propionate, 176 µg/d (6-11 years old), or 220 µg/d (12-16 years old). Main Outcomes and Measures: The primary outcome was the time to a severe asthma exacerbation. Secondary outcomes included the time to a viral-induced severe exacerbation, the proportion of participants in whom the dose of inhaled corticosteroid was reduced halfway through the trial, and the cumulative fluticasone dose during the trial. Results: Among 192 randomized participants (mean age, 9.8 years; 77 girls [40%]), 180 (93.8%) completed the trial. A total of 36 participants (37.5%) in the vitamin D3 group and 33 (34.4%) in the placebo group had 1 or more severe exacerbations. Compared with placebo, vitamin D3 supplementation did not significantly improve the time to a severe exacerbation: the mean time to exacerbation was 240 days in the vitamin D3 group vs 253 days in the placebo group (mean group difference, -13.1 days [95% CI, -42.6 to 16.4]; adjusted hazard ratio, 1.13 [95% CI, 0.69 to 1.85]; P = .63). Vitamin D3 supplementation, compared with placebo, likewise did not significantly improve the time to a viral-induced severe exacerbation, the proportion of participants whose dose of inhaled corticosteroid was reduced, or the cumulative fluticasone dose during the trial. Serious adverse events were similar in both groups (vitamin D3 group, n = 11; placebo group, n = 9). Conclusions and Relevance: Among children with persistent asthma and low vitamin D levels, vitamin D3 supplementation, compared with placebo, did not significantly improve the time to a severe asthma exacerbation. The findings do not support the use of vitamin D3 supplementation to prevent severe asthma exacerbations in this group of patients. Trial Registration: ClinicalTrials.gov Identifier: NCT02687815.

Effects of Collaborative Care for Comorbid Attention Deficit Hyperactivity Disorder Among Children With Behavior Problems in Pediatric Primary Care.

This study evaluates the impact of a 6-month care management intervention for 206 children diagnosed with comorbid attention deficit hyperactivity disorder (ADHD) from a sample of 321 five- to 12-year-old children recruited for treatment of behavior problems in 8 pediatric primary care offices. Practices were cluster-randomized to Doctor Office Collaboration Care (DOCC) or Enhanced Usual Care (EUC). Chart reviews documented higher rates of service delivery, prescription of medication for ADHD, and titration in DOCC (vs EUC). Based on complex conditional models, DOCC showed greater acute improvement in individualized ADHD treatment goals and follow-up improvements in quality of life and ADHD and oppositional defiant disorder goals. Medication use had a significant effect on acute and follow-up ADHD symptom reduction and quality of life. Medication continuity was associated with some long-term gains. A collaborative care intervention for behavior problems that incorporated treatment guidelines for ADHD in primary care was more effective than psychoeducation and facilitated referral to community treatment.

Initiating Nutritional Support Before 72 Hours Is Associated With Favorable Outcome After Severe Traumatic Brain Injury in Children: A Secondary Analysis of a Randomized, Controlled Trial of Therapeutic Hypothermia.

OBJECTIVES: To understand the relationship between the timing of initiation of nutritional support in children with severe traumatic brain injury and outcomes. DESIGN: Secondary analysis of a randomized, controlled trial of therapeutic hypothermia (Pediatric Traumatic Brain Injury Consortium: Hypothermia, also known as "the Cool Kids Trial" (NCT 00222742). SETTINGS: Fifteen clinical sites in the United States, Australia, and New Zealand. SUBJECTS: Inclusion criteria included 1) age less than 18 years, 2) postresuscitation Glasgow Coma Scale less than or equal to 8, 3) Glasgow Coma Scale motor score less than 6, and 4) available to be randomized within 6 hours after injury. Exclusion criteria included normal head CT, Glasgow Coma Scale equals to 3, hypotension for greater than 10 minutes (< fifth percentile for age), uncorrectable coagulopathy, hypoxia (arterial oxygen saturation < 90% for > 30 min), pregnancy, penetrating injury, and unavailability of a parent or guardian to consent at centers without emergency waiver of consent. INTERVENTIONS: Therapeutic hypothermia (32-33°C for 48 hr) followed by slow rewarming for the primary study. For this analysis, the only intervention was the extraction of data regarding nutritional support from the existing database. MEASUREMENTS AND MAIN RESULTS: Timing of initiation of nutritional support was determined and patients stratified into four groups (group 1-no nutritional support over first 7 d; group 2-nutritional support initiated < 48 hr after injury; group 3-nutritional support initiated 48 to < 72 hr after injury; group 4-nutritional support initiated 72-168 hr after injury). Outcomes were also stratified (mortality and Glasgow Outcomes Scale-Extended for Pediatrics; 1-4, 5-7, 8) at 6 and 12 months. Mixed-effects models were performed to define the relationship between nutrition and outcome. Children (n = 90, 77 randomized, 13 run-in) were enrolled (mean Glasgow Coma Scale = 5.8); the mortality rate was 13.3%. 57.8% of subjects received hypothermia Initiation of nutrition before 72 hours was associated with survival (p = 0.01), favorable 6 months Glasgow Outcomes Scale-Extended for Pediatrics (p = 0.03), and favorable 12 months Glasgow Outcomes Scale-Extended for Pediatrics (p = 0.04). Specifically, groups 2 and 3 had favorable outcomes versus group 1. CONCLUSIONS: Initiation of nutritional support before 72 hours after traumatic brain injury was associated with decreased mortality and favorable outcome in this secondary analysis. Although this provides a rationale to initiate nutritional support early after traumatic brain injury, definitive studies that control for important covariates (severity of injury, clinical site, calories delivered, parenteral/enteral routes, and other factors) are needed to provide definitive evidence on the optimization of the timing of nutritional support after severe traumatic brain injury in children.

Adjunctive Bright Light Therapy for Bipolar Depression: A Randomized Double-Blind Placebo-Controlled Trial.

OBJECTIVE: Patients with bipolar disorder have recurrent major depression, residual mood symptoms, and limited treatment options. Building on promising pilot data, the authors conducted a 6-week randomized double-blind placebo-controlled trial to investigate the efficacy of adjunctive bright light therapy at midday for bipolar depression. The aims were to determine remission rate, depression symptom level, and rate of mood polarity switch, as well as to explore sleep quality. METHOD: The study enrolled depressed adults with bipolar I or II disorder who were receiving stable dosages of antimanic medication (excluding patients with hypomania or mania, mixed symptoms, or rapid cycling). Patients were randomly assigned to treatment with either 7,000-lux bright white light or 50-lux dim red placebo light (N=23 for each group). Symptoms were assessed weekly with the Structured Interview Guide for the Hamilton Depression Scale With Atypical Depression Supplement (SIGH-ADS), the Mania Rating Scale, and the Pittsburgh Sleep Quality Index. Remission was defined as having a SIGH-ADS score of 8 or less. RESULTS: At baseline, both groups had moderate depression and no hypomanic or manic symptoms. Compared with the placebo light group, the group treated with bright white light experienced a significantly higher remission rate (68.2% compared with 22.2%; adjusted odds ratio=12.6) at weeks 4-6 and significantly lower depression scores (9.2 [SD=6.6] compared with 14.9 [SD=9.2]; adjusted ß=-5.91) at the endpoint visit. No mood polarity switches were observed. Sleep quality improved in both groups and did not differ significantly between them. CONCLUSIONS: The data from this study provide robust evidence that supports the efficacy of midday bright light therapy for bipolar depression.

Phase I randomized clinical trial of N-acetylcysteine in combination with an adjuvant probenecid for treatment of severe traumatic brain injury in children.

BACKGROUND: There are no therapies shown to improve outcome after severe traumatic brain injury (TBI) in humans, a leading cause of morbidity and mortality. We sought to verify brain exposure of the systemically administered antioxidant N-acetylcysteine (NAC) and the synergistic adjuvant probenecid, and identify adverse effects of this drug combination after severe TBI in children. METHODS: IRB-approved, randomized, double-blind, placebo controlled Phase I study in children 2 to 18 years-of-age admitted to a Pediatric Intensive Care Unit after severe TBI (Glasgow Coma Scale [GCS] score ≤8) requiring an externalized ventricular drain for measurement of intracranial pressure (ICP). Patients were recruited from November 2011-August 2013. Fourteen patients (n = 7/group) were randomly assigned after obtaining informed consent to receive probenecid (25 mg/kg load, then 10 mg/kg/dose q6h×11 doses) and NAC (140 mg/kg load, then 70 mg/kg/dose q4h×17 doses), or placebos via naso/orogastric tube. Serum and CSF samples were drawn pre-bolus and 1-96 h after randomization and drug concentrations were measured via UPLC-MS/MS. Glasgow Outcome Scale (GOS) score was assessed at 3 months. RESULTS: There were no adverse events attributable to drug treatment. One patient in the placebo group was withdrawn due to adverse effects. In the treatment group, NAC concentrations ranged from 16,977.3±2,212.3 to 16,786.1±3,285.3 in serum and from 269.3±113.0 to 467.9±262.7 ng/mL in CSF, at 24 to 72 h post-bolus, respectively; and probenecid concentrations ranged from 75.4.3±10.0 to 52.9±25.8 in serum and 5.4±1.0 to 4.6±2.1 µg/mL in CSF, at 24 to 72 h post-bolus, respectively (mean±SEM). Temperature, mean arterial pressure, ICP, use of ICP-directed therapies, surveillance serum brain injury biomarkers, and GOS at 3 months were not different between groups. CONCLUSIONS: Treatment resulted in detectable concentrations of NAC and probenecid in CSF and was not associated with undesirable effects after TBI in children. TRIAL REGISTRATION: ClinicalTrials.gov NCT01322009.

Brief, unidimensional melancholia rating scales are highly sensitive to the effect of citalopram and may have biological validity: implications for the research domain criteria (RDoC).

BACKGROUND: Most depression rating scales are multidimensional and the resulting heterogeneity may impede identification of coherent biomarkers. The aim of this study was to compare the psychometric performance of the multidimensional 17-item Hamilton Depression Rating Scale (HAM-D17) and the 30-item Inventory of Depressive Symptomatology (IDS-C30) to that of their unidimensional six-item melancholia subscales (HAM-D6 and IDS-C6). METHODS: A total of 2242 subjects from level 1 (citalopram) of the Sequenced Treatment Alternatives to Relieve Depression (STAR* study were included in the analysis. Symptom change, response and remission rates were compared for HAM-D6 versus HAM-D17 and for IDS-C6 versus IDS-C30. The changes in total scores on these scales were compared to the change in Quality of Life Enjoyment and Satisfaction Questionnaire (QLES-Q) score using correlation analysis. RESULTS: The response to treatment was significantly greater according to the HAM-D6 and IDS-C6. Furthermore, the correlation of changes in depression-ratings with changes in QLES-Q scores were comparable for the subscales and full scales. LIMITATIONS: STAR*D was not designed to answer the research questions addressed in this analysis. CONCLUSIONS: Our findings indicate that the HAM-D6 and IDS-C6 melancholia scales capture a coherent construct in depression. The syndrome reflected in these scales is unidimensional, sensitive to specific pharmacological intervention, and therefore likely to have biological validity. We therefore believe that "melancholia" thus defined could be a valuable construct under the Research Domain Criteria (RDoC), which specifically aims at identifying the neurobiology underlying mental disorders and providing drugable targets.

The effect of sildenafil on quality of life.

BACKGROUND: Antidepressant-induced sexual dysfunction affects approximately 50% of patients taking antidepressants. Previous research has explored sildenafil's effectiveness in treating various forms of erectile dysfunction, but there is no research supporting sildenafil's use for improving the quality of life for patients with sexual dysfunction linked to antidepressant use. The authors of this article aimed to assess the improvements in quality of life in patients taking sildenafil to treat antidepressant-induced sexual dysfunction. METHODS: One hundred and two out of 2,239 male and female patients in the follow-up phase of the Sequenced Treatment Alternatives to Relieve Depression antidepressant trials who complained of sexual dysfunction were given sildenafil, 50 to 100 mg, as needed. After 12 months, we measured patients' change in libido, sexual drive, family relationships, overall well-being, satisfaction with treatment, and overall contentment with items on the 17-item Hamilton Depression Rating Scale, Quality of Life Enjoyment and Satisfaction Questionnaire, 30-item Inventory of Depressive Symptoms, and 12-item Short Form Health Survey. RESULTS: There was a significant association between sildenafil use and improvement in libido and sexual drive by month 6. There was no significant improvement in the quality-of-life scores we examined, but treatment satisfaction and overall contentment increased over time. CONCLUSIONS: Despite no direct association with sildenafil use and quality-of-life scores, sildenafil may be a beneficial treatment for antidepressant-induced sexual dysfunction. A double-blind, placebo-controlled study of sildenafil in antidepressant-induced sexual dysfunction is needed to further explore its potential benefits.

Impact of changing the measles vaccine vial size on Niger's vaccine supply chain: a computational model.

BACKGROUND: Many countries, such as Niger, are considering changing their vaccine vial size presentation and may want to evaluate the subsequent impact on their supply chains, the series of steps required to get vaccines from their manufacturers to patients. The measles vaccine is particularly important in Niger, a country prone to measles outbreaks. METHODS: We developed a detailed discrete event simulation model of the vaccine supply chain representing every vaccine, storage location, refrigerator, freezer, and transport device (e.g., cold trucks, 4 × 4 trucks, and vaccine carriers) in the Niger Expanded Programme on Immunization (EPI). Experiments simulated the impact of replacing the 10-dose measles vial size with 5-dose, 2-dose and 1-dose vial sizes. RESULTS: Switching from the 10-dose to the 5-dose, 2-dose and 1-dose vial sizes decreased the average availability of EPI vaccines for arriving patients from 83% to 82%, 81% and 78%, respectively for a 100% target population size. The switches also changed transport vehicle's utilization from a mean of 58% (range: 4-164%) to means of 59% (range: 4-164%), 62% (range: 4-175%), and 67% (range: 5-192%), respectively, between the regional and district stores, and from a mean of 160% (range: 83-300%) to means of 161% (range: 82-322%), 175% (range: 78-344%), and 198% (range: 88-402%), respectively, between the district to integrated health centres (IHC). The switch also changed district level storage utilization from a mean of 65% to means of 64%, 66% and 68% (range for all scenarios: 3-100%). Finally, accounting for vaccine administration, wastage, and disposal, replacing the 10-dose vial with the 5 or 1-dose vials would increase the cost per immunized patient from $0.47US to $0.71US and $1.26US, respectively. CONCLUSIONS: The switch from the 10-dose measles vaccines to smaller vial sizes could overwhelm the capacities of many storage facilities and transport vehicles as well as increase the cost per vaccinated child.

The efficacy of omega-3 supplementation for major depression: a randomized controlled trial.

OBJECTIVE: To document the short-term efficacy of omega-3 supplementation in reducing depressive symptoms in patients experiencing a major depressive episode (MDE). METHOD: Inclusive, double-blind, randomized, controlled, 8-week, parallel-group trial, conducted October 17, 2005 through January 30, 2009 in 8 Canadian academic and psychiatric clinics. Adult outpatients (N = 432) with MDE (Mini-International Neuropsychiatric Interview, version 5.0.0, criteria) lasting at least 4 weeks, including 40.3% taking antidepressants at baseline, were randomly assigned to 8 weeks of 1,050 mg/d of eicosapentaenoic acid (EPA) and 150 mg/d of docosahexaenoic acid (DHA) or matched sunflower oil placebo (2% fish oil). The primary outcome was the self-report Inventory of Depressive Symptomatology (IDS-SR(30)); the secondary outcome was the clinician-rated Montgomery-Åsberg Depression Rating Scale (MADRS). RESULTS: The adjusted mean difference between treatment and placebo was 1.32 points (95% CI, -0.20 to 2.84; P = .088) on the IDS-SR(30) and 0.97 points (95% CI, -0.012 to 1.95; P = .053) on the MADRS. Planned subgroup analyses revealed a significant interaction of comorbid anxiety disorders and study group (P = .035). For patients without comorbid anxiety disorders (n = 204), omega-3 supplementation was superior to placebo, with an adjusted mean difference of 3.17 points on the IDS-SR(30) (95% CI, 0.89 to 5.45; P = .007) and 1.93 points (95% CI, 0.50 to 3.36; P = .008) on the MADRS. CONCLUSIONS: In this heterogeneous sample of patients with MDE, there was only a trend toward superiority of omega-3 supplementation over placebo in reducing depressive symptoms. However, there was a clear benefit of omega-3 supplementation among patients with MDE without comorbid anxiety disorders. TRIAL REGISTRATION: controlled-trials.com Identifier: ISRCTN47431149.

Mechanical vs manual manipulation for low back pain: an observational cohort study.

OBJECTIVE: This is an observational prospective cohort study to explore the treatment effect of mechanical vs manual manipulation for acute low back pain. METHODS: Ninety-two patients with a history of acute low back pain were recruited from 3 private chiropractic offices, 2 of which used manual lumbar manipulation and 1 used mechanical instrument manipulation (Activator) as their primary modes of treatment. The chiropractors used their "treatment-as-usual" protocols for a maximum of 8 visits or 4 weeks, whichever occurred first. Primary outcome measures were changes in Numeric Pain Rating Scale (NPRS) and Oswestry Disability Index (ODI) scores from baseline to 4 weeks. The linear regression models were adjusted for baseline NPRS and ODI scores, age, and treatment expectancy. RESULTS: Comparison of baseline characteristics did not show any significant differences between the groups except for age (38.4 vs 49.7 years, P < .001) and treatment expectancy (5.7 vs 6.3, P = .003). Linear regression revealed significantly lower NPRS scores in the manual manipulation group at 4 weeks (beta = -1.2; 95% confidence interval, -2.1 to -.28) but no significant difference in ODI scores between the 2 groups at 4 weeks (beta = 1.5; 95% confidence interval, -8.3 to 2.4). Treatment expectancy, but not age, was found to have a significant main effect on both NPRS and ODI scores at 4 weeks. Exploratory analysis of the clinical patterns of care between the clinicians revealed significant differences in treatment frequency, duration, modality, and radiograph use between the 2 cohorts. CONCLUSIONS: This study highlights the challenges inherent with conducting research that allows for "treatment as usual." The data and experience derived from this investigational study will be used to design a future randomized clinical trial in which tighter controls will be imposed on the treatment protocol.

A direct comparison of presenting characteristics of depressed outpatients from primary vs. specialty care settings: preliminary findings from the STAR*D clinical trial.

PURPOSE: No study has directly compared the clinical features of depression for patients entering clinical trials using identical enrollment criteria at primary care (PC) and specialty care (SC) settings. The Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study (http://www.star-d.org) provides a unique opportunity to provide this comparison for patients with a major depressive disorder (MDD) requiring treatment. SUBJECTS AND METHODS: We report baseline data for the first 1500 patients enrolled in this trial involving 41 clinic sites (18 PC, 23 SC). Broadly inclusive eligibility criteria required that patients have a DSM-IV diagnosis of nonpsychotic MDD, have not failed an adequate medication trial during their current episode and score>or=14 on the 17-item Hamilton Rating Scale for Depression (HAM-D17). Primary outcomes included the 30-item Inventory of Depressive Symptomatology-Clinician-Rated (IDS-C30) and the HAM-D17. RESULTS: Specialty care and PC patients had equivalent degrees of depressive severity (IDS-C30=35.8; HAM-D17=20.4). Specialty care patients were almost twice as likely to report a prior suicide attempt than PC patients (21% vs. 12%, P<.0001) and slightly less likely to endorse suicidal ideation in the past week (45.0% vs. 50.8%, P=.006). The only other distinguishing core symptoms were a slightly lower likelihood of PC patients endorsing depressed mood (95.2% vs. 97.7%, P=.032) or anhedonia (66.3% vs. 70.7%, P=.042, IDS-C30) and a lower likelihood of PC patients endorsing weight loss (IDS-C30). HAM-D17 results were identical. CONCLUSION: Depressive severity was not different, and symptomatic presentations did not differ substantially. Major depressive disorder is more similar than different among patients at SC and PC settings. Thus, similar clinical and research methods for screening, detecting and measuring treatment outcomes can be applied in both settings.

Prevalence and clinical correlates of irritability in major depressive disorder: a preliminary report from the Sequenced Treatment Alternatives to Relieve Depression study.

BACKGROUND: Irritability is a common feature of major depressive disorder (MDD), though it is not included in the DSM-IV diagnostic criteria for adult MDD and is not assessed in most standard depression rating scales. Irritability with or without depression has been associated with risk for suicide, violence, and cardiovascular disease. METHOD: The prevalence of significant levels of irritability was examined among the first 1456 outpatients with nonpsychotic MDD entering the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study. Sociodemographic and clinical features were compared for participants who did and did not report irritability at least 50% of the time during the week preceding study entry. RESULTS: Of 1456 evaluable subjects, 582 (40%) reported irritability more than half the time. These individuals were more likely than nonirritable subjects to be female, to be younger, to be unemployed, and to report a history of at least 1 suicide attempt. Functional status and quality of life were also poorer in this group. Irritability was correlated with overall depressive severity, which accounted for nearly all of the clinical differences noted, with the exception of vascular disease, for which the association persisted after controlling for age, sex, and depressive severity. CONCLUSION: Irritability is prevalent among depressed outpatients and associated with a greater likelihood of suicide attempts, poorer functional status, and greater prevalence of vascular disease. It is correlated with overall depression severity and thus may not represent a distinct depressive subtype per se. The impact of irritability on course and treatment outcome merits further study.

Methods of testing feasibility for sequenced treatment alternatives to relieve depression (STAR*D).

In large multi-site trials, a feasibility or pilot study can be crucial to test the functionality of all aspects of conducting the study prior to the initiation of the formal study. A feasibility trial was conducted for the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) Project, a multi-site, prospective, sequentially randomized, clinical trial of outpatients with nonpsychotic major depressive disorder. From 14 December 2000 to 8 June 2001, 42 patients were screened for enrollment into the STAR*D Feasibility Trial. Twenty-four patients who were eligible and consented to participate were treated with citalopram for up to 12 weeks. During the course of this trial, issues were raised that resulted in modifications to the study procedures. Modifications made as a result of this trial affected four domains: (1) communication, (2) patient and provider burden, (3) data collection forms, and (4) recruitment and retention of subjects. This paper describes what was learned during the STAR*D Feasibility Trial so researchers planning to conduct similar trials can learn the practical issues related to conducting such a research project. While the information gathered was useful, it did delay the initiation of the formal trial. We view this cost as an investment in the development of overall study procedures that should lead to a stronger study.