Conducting an antidepressant clinical trial in oncology: challenges and strategies to address them.

OBJECTIVE: The aim of this report is to discuss the design of an antidepressant clinical trial and discuss the challenges and potential solutions to these challenges to successful recruitment of oncology patients for psychopharmacology trials. METHOD: We utilize meeting minutes and investigator discussions to identify the modifiable and nonmodifiable variables that affected successful subject recruitment for this study. RESULTS: No subjects were enrolled in our placebo-controlled antidepressant trial. After study modification to remove the placebo arm, we enrolled 21 subjects with depression and cancer. We identified the following recruitment difficulties during the study: diagnostic ambiguity in patients with depression and cancer, lowered subject retention in a medically ill population, patient reluctance to enroll in placebo-controlled studies and lack of a standardized referral processes for antidepressant studies in oncology at our institution. CONCLUSION: Our experience provides guidance on specific factors that future clinicians and researchers can consider when implementing psychopharmacologic trials in the medically ill.

A pilot study to evaluate symptom-oriented selection of antidepressants in patients with cancer.

BACKGROUND: Major depressive disorder (MDD) is a common and debilitating illness in patients with cancer. However, the optimal treatment of depression in these patients remains uncertain, with limited evidence to support the use of pharmacologic therapy. We conducted a pilot study to evaluate the feasibility of an antidepressant clinical trial in the oncology population and the process of symptom-oriented selection of antidepressants (citalopram or mirtazapine) in patients with cancer and MDD. METHODS: This was a single center, two-arm, nonrandomized, open-label, nine-week pilot study of mirtazapine or citalopram in cancer patients with MDD. The primary endpoint was the feasibility to recruit and to retain patients. Secondary outcomes included changes in Patient Health Questionnaire-9 (PHQ-9) (depression), Functional Assessment of Cancer Therapy-General (FACT-G) (quality of life), Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) (fatigue), and Pittsburgh Sleep Quality Index (PSQI) (sleep). We conducted descriptive statistics and responder analyses. RESULTS: Of 21 patients, 18 (86%) successfully completed the study. An average of 2.8 subjects were enrolled per month. Mean scores on the PHQ-9 improved overall by 6.4 points (95% confidence interval [CI] 3.6-9.2). Additionally, mean FACT-G, FACIT-Fatigue, and PSQI scores improved in both study arms. CONCLUSION: Conducting antidepressant clinical trials is challenging in the oncology population. We approached but did not meet our feasibility goals. Depression and quality of life (QOL) scores improved with both mirtazapine and citalopram, but evidence-based pharmacologic treatments for depression in cancer patients are needed.

Multisegment foot motion during gait: proof of concept in rheumatoid arthritis.

OBJECTIVE: To test a multisegment foot model for kinematic analysis during barefoot walking in patients with well established rheumatoid arthritis (RA) and foot impairments. METHODS: Five healthy adult subjects and 11 RA patients with advanced disease were studied. Foot impairments were assessed using standardized outcomes and clinical examination techniques. A 6-camera 60 Hz video-based motion analysis system was used to measure motion of the shank, rearfoot, forefoot, and hallux segments and the vertical displacement of the navicular. Face validity and estimates of repeatability were determined. Motion patterns were calculated and comparisons were made between healthy subjects and patients with RA. Relationships between clinical impairment and abnormal motion were determined through inspection of individual RA cases. RESULTS: Across the motion variables, the within-day and between-day coefficient of multiple correlation values ranged from 0.677 to 0.982 for the healthy subjects and 0.830 to 0.981 for RA patients. Based on previous studies, motion parameters for the healthy subjects showed excellent face validity. In RA patients, there was reduced range of motion across all segments and all planes of motion, which was consistent with joint stiffness. In the RA patients, rearfoot motion was shifted towards eversion and external rotation and peak values for these variables were increased, on average, by 7 degrees and 11 degrees, respectively. Forefoot range of motion was reduced in all 3 planes (between 31% and 53%), but the maximum and minimum angles were comparable to normal. The navicular height, during full foot contact, was on average 3 mm lower in the RA patients in comparison to normal. The hallux was less extended in the RA subjects in comparison to normal (21 degrees vs 33 degrees) during the terminal stance phase. Individual cases showed abnormal patterns of motion consistent with their clinical impairments, especially those with predominant forefoot pain or pes planovalgus. CONCLUSION: In RA, multisegment foot models may provide a more complete description of foot motion abnormalities where pathology presents at multiple joints, leading to complex and varied patterns of impairment. This technique may be useful to evaluate functional changes in the foot and to help plan and assess logical, structurally based corrective interventions.