A novel application of the Intent to Attend assessment to reduce bias due to missing data in a randomized controlled clinical trial.

BACKGROUND: Missing data are unavoidable in most randomized controlled clinical trials, especially when measurements are taken repeatedly. If strong assumptions about the missing data are not accurate, crude statistical analyses are biased and can lead to false inferences. Furthermore, if we fail to measure all predictors of missing data, we may not be able to model the missing data process sufficiently. In longitudinal randomized trials, measuring a patient's intent to attend future study visits may help to address both of these problems. Leon et al. developed and included the Intent to Attend assessment in the Lithium Treatment - Moderate dose Use Study (LiTMUS), aiming to remove bias due to missing data from the primary study hypothesis. PURPOSE: The purpose of this study is to assess the performance of the Intent to Attend assessment with regard to its use in a sensitivity analysis of missing data. METHODS: We fit marginal models to assess whether a patient's self-rated intent predicted actual study adherence. We applied inverse probability of attrition weighting (IPAW) coupled with patient intent to assess whether there existed treatment group differences in response over time. We compared the IPAW results to those obtained using other methods. RESULTS: Patient-rated intent predicted missed study visits, even when adjusting for other predictors of missing data. On average, the hazard of retention increased by 19% for every one-point increase in intent. We also found that more severe mania, male gender, and a previously missed visit predicted subsequent absence. Although we found no difference in response between the randomized treatment groups, IPAW increased the estimated group difference over time. LIMITATIONS: LiTMUS was designed to limit missed study visits, which may have attenuated the effects of adjusting for missing data. Additionally, IPAW can be less efficient and less powerful than maximum likelihood or Bayesian estimators, given that the parametric model is well specified. CONCLUSIONS: In LiTMUS, the Intent to Attend assessment predicted missed study visits. This item was incorporated into our IPAW models and helped reduce bias due to informative missing data. This analysis should both encourage and facilitate future use of the Intent to Attend assessment along with IPAW to address missing data in a randomized trial.

Discovery and development of lamotrigine for bipolar disorder: a story of serendipity, clinical observations, risk taking, and persistence.

This paper briefly reviews and comments on the development of lamotrigine as a treatment for bipolar disorder. The events described include astute clinical observations by epileptologists, serendipitous coupling of the drug's clinical profile to unmet need of two refractory bipolar patients by a practicing psychiatrist, risk taking on the part of an industry sponsor, and persistence on the part of a few key internal and external advocates to see development through to its conclusion, taking place against a backdrop of a disease area which, at the time of the earliest events described here, had not seen the development of any new pharmacologic treatments for decades. Fortunately for patients, since that time there has been a veritable explosion of research into treatments for bipolar disorder, both old and new, so that now patients and physicians have multiple evidence-based options for the treatment of this devastating illness. The development of lamotrigine provides one example of the importance of prescience, patience and persistence in bringing a novel idea to clinical fruition.

Treatment characteristics and illness burden among European Americans, African Americans, and Latinos in the first 2,000 patients of the systematic treatment enhancement program for bipolar disorder.

OBJECTIVE: Across ethnicity/race, prevalence rates of bipolar disorder are similar. However, African Americans and Latinos may receive less specialty mental health treatment and different medications, and may be less adherent to treatment regimens than European American patients. This study compared illness characteristics, treatment history, and overall functioning in a sample of European American, African American, and Latino patients with bipolar disorder. METHODS: The samples were drawn from the first 2,000 patients enrolled in the Systematic Treatment Enhancement Program for Bipolar Disorder. There were 1,686 European Americans, 65 African Americans, and 77 Latinos. The data were collected upon study entry, with structured interviews, clinicianrated forms, and self report. RESULTS: African Americans had a greater likelihood of psychosis and fewer psychiatric medication prescriptions than did European Americans. Latinos had greater alcohol comorbidity, fewer psychiatric medication prescriptions and specialty treatment visits, and more frequent religious service attendance than did European Americans. Depression and manic episode severity and functional outcomes were similar across groups. CONCLUSIONS: Patients with bipolar disorder who are members of ethnic/racial minority groups continue to receive less intensive specialized mental health treatment than do European American patients. These findings may be related to provider, patient, or provider-patient relationship variables. Despite treatment differences and greater comorbidity and sympomatology, there were no differences among the three groups in overall functioning, suggesting additional outcome measurement is warranted.

Factors associated with stigma among caregivers of patients with bipolar disorder in the STEP-BD study.

OBJECTIVE: Little is known about the factors contributing to mental illness stigma among caregivers of people with bipolar disorder. METHODS: A total of 500 caregivers of patients participating in the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD) study were interviewed in a cross-sectional design on measures of stigma, mood, burden, and coping. Relatives and friends with bipolar disorder were assessed on measures of diagnosis and clinical status, determined by a days-well measure derived from psychiatrist ratings of DSM-IV episode status. Because patients' clinical status varied widely, separate models were run for patients who were euthymic for at least three-fourths of the past year (well group) and for those who met criteria for an affective episode for at least one-fourth of the previous year (unwell group). Stepwise multiple regression was used to identify patient, illness, and caregiver characteristics associated with caregiver stigma. RESULTS: In the unwell group, greater mental illness stigma was associated with bipolar I (versus II) disorder, less social support for the caregiver, fewer caregiver social interactions, and being a caregiver of Hispanic descent. In the well group, greater stigma was associated with being a caregiver who is the adult child of a parent with bipolar disorder, who has a college education, who has fewer social interactions, and who cares for a female bipolar patient. CONCLUSIONS: Mental illness stigma was found to be prevalent among caregivers of persons with bipolar disorder who have active symptoms as well as for caregivers of those who have remitted symptoms. Stigma is typically associated with factors identifying patients as "different" during symptomatic periods. Research is needed to understand how the stigma experienced by caregivers during stable phases of illness differs from the stigma experienced during patients' illness states.

Pharmacotherapy for bipolar depression: an economic assessment.

Bipolar disorder (BPD) is a common, severe and recurrent mood disorder associated with high rates of comorbidities, suicide, dysfunction and a high socioeconomic burden. Although the management of BPD has traditionally focused on the acute treatment of mania, the chronic nature of BPD necessitates long-term maintenance treatment. Bipolar depression is the predominant abnormal affective pole and causes greater disability and economic burden than mania. Maintenance pharmacotherapy can reduce rates of future episodes, and subsequently, the associated risks, functional disability and economic burden of bipolar illness.