Analysis and Interpretation of Results Based on Patient-Reported Outcomes

AbstractThis article is part of a series of manuscripts dealing with the incorporation of patient-reported outcomes (PROs) into clinical trials. The issues dealt with in this manuscript concern the common pitfalls to avoid in statistical analysis and interpretation of PROs. Specifically, the questions addressed by this manuscript involve the analysis pitfalls with PRO data in clinical trials and how can they be avoided (e.g.,missing data, multiplicity, null results etc.). The manuscript provides key literature for existing resources and proposes new guidelines

Interpreting and Reporting Results Based on Patient-Reported Outcomes

AbstractThis article deals with the incorporation of patient-reported outcomes (PROs) into clinical trials and focuses on issues associated with the interpretation and reporting of PRO data. The primary focus and context of this information relates to the evidentiary support and reporting for a labeling or advertising claim of a PRO benefit for a new or approved pharmaceutical product. This manuscript focuses on issues associated with assessing clinical significance and common pitfalls to avoid in presenting results related to PROs. Specifically, the questions addressed by this manuscript involve: What are the best methods to assess clinical significance for PROs? How should investigators present PRO data most effectively in a Food and Drug Administration (FDA) application? In labeling or in a scientific publication? Guidelinesfor interpreting clinical significance of PROs and for comprehensively reporting on the methods, measures and results of clinical trials that incorporate PROs are important for clinicians, regulatory agencies, and most of all to patients. Clear specifications for considering a finding on a PRO measure, as clinically meaningful, need to be determined by instrument developers and psychometricians; they need to be reported for all clinical trials involving PRO end points. Clinical trial reports need to be comprehensive, clear, and sufficient to enable any reader to understand the methods, PRO measures, statistical analysis, and results

The Mayo Clinic Manuscript Series Relative to the Discussion, Dissemination, and Operationalization of the Food and Drug Administration Guidance on Patient-Reported Outcomes

AbstractPatient-reported outcomes (PROs) have become increasingly prevalent in clinical research and practice. On February 2, 2006, the Food and Drug Administration (FDA) released a draft guidance document with respect to incorporating PROs into clinical research endeavors which include FDA involvement. Researchers at the Mayo Clinic worked with FDA personnel and experts from academia, industry, clinical research, and clinical practice to facilitate discussion, dissemination, and operationalization of the FDA guidance document. This article introduces a manuscript series that resulted from this collective effort. Basic terms are definedand a précis of each article in the manuscript series is given. The ultimate conclusion to be drawn from this series is that, while the goals of assessing and analyzing PRO elements of clinical practice and research are challenging, there now exists a scientific foundation that makes achieving these goals feasible and the results credible. This is vitally important because after all, at the heart of all healthcare endeavors is the patient

Effects of Carpal Tunnel Syndrome on Dexterous Manipulation Are Grip Type-Dependent

Carpal tunnel syndrome (CTS) impairs sensation of a subset of digits. Although the effects of CTS on manipulation performed with CTS-affected digits have been studied using precision grip tasks, the extent to which CTS affects multi-digit force coordination has only recently been studied. Whole-hand manipulation studies have shown that CTS patients retain the ability to modulate multi-digit forces to object mass, mass distribution, and texture. However, CTS results in sensorimotor deficits relative to healthy controls, including significantly larger grip force and lower ability to balance the torques generated by the digits. Here we investigated the effects of CTS on multi-digit force modulation to object weight when manipulating an object with a variable number of fingers. We hypothesized that CTS patients would be able to modulate digit forces to object weight. However, as different grip types involve the exclusive use of CTS-affected digits (‘uniform’ grips) or a combination of CTS-affected and non-affected digits (‘mixed’ grips), we addressed the question of whether ‘mixed’ grips would reduce or worsen CTS-induced force coordination deficits. The former scenario would be due to adding digits with intact tactile feedback, whereas the latter scenario might occur due to a potentially greater challenge for the central nervous system of integrating ‘noisy’ and intact tactile feedback. CTS patients learned multi-digit force modulation to object weight regardless of grip type. Although controls exerted the same total grip force across all grip types, patients exerted significantly larger grip force than controls but only for manipulations with four and five digits. Importantly, this effect was due to CTS patients’ inability to change the finger force distribution when adding the ring and little fingers. These findings suggest that CTS primarily challenges sensorimotor integration processes for dexterous manipulation underlying the coordination of CTS-affected and non-affected digits

Effects of Carpal Tunnel Syndrome on adaptation of multi-digit forces to object mass distribution for whole-hand manipulation

Background Carpal tunnel syndrome (CTS) is a compression neuropathy of the median nerve that results in sensorimotor deficits in the hand. Until recently, the effects of CTS on hand function have been studied using mostly two-digit grip tasks. The purpose of this study was to investigate the coordination of multi-digit forces as a function of object center of mass (CM) during whole-hand grasping. Methods Fourteen CTS patients and age- and gender-matched controls were instructed to grasp, lift, hold, and release a grip device with five digits for seven consecutive lifts while maintaining its vertical orientation. The object CM was changed by adding a mass at different locations at the base of the object. We measured forces and torques exerted by each digit and object kinematics and analyzed modulation of these variables to object CM at object lift onset and during object hold. Our task requires a modulation of digit forces at and after object lift onset to generate a compensatory moment to counteract the external moment caused by the added mass and to minimize object tilt. Results We found that CTS patients learned to generate a compensatory moment and minimized object roll to the same extent as controls. However, controls fully exploited the available degrees of freedom (DoF) in coordinating their multi-digit forces to generate a compensatory moment, i.e., digit normal forces, tangential forces, and the net center of pressure on the finger side of the device at object lift onset and during object hold. In contrast, patients modulated only one of these DoFs (the net center of pressure) to object CM by modulating individual normal forces at object lift onset. During object hold, however, CTS patients were able to modulate digit tangential force distribution to object CM. Conclusions Our findings suggest that, although CTS did not affect patients’ ability to perform our manipulation task, it interfered with the modulation of specific grasp control variables. This phenomenon might be indicative of a lower degree of flexibility of the sensorimotor system in CTS to adapt to grasp task conditions

Lenalidomide and dexamethasone in patients with relapsed multiple myeloma and impaired renal function: PrE1003, a PrECOG study

Renal insufficiency is common in patients with relapsed multiple myeloma and can often limit choice of therapy. Lenalidomide, a critical agent in the treatment of relapsed multiple myeloma, is renally cleared., This phase I/II trial evaluated the efficacy and safety of lenalidomide with dexamethasone in patients with relapsed multiple myeloma and renal insufficiency. Three groups were treated, with creatinine clearance 30–60 cc/hr (group A), CrCl \u3c 30 not on dialysis (group B), and patients on dialysis (group C) at escalating doses of lenalidomide. A total of 63 patients were treated and no DLTs were observed in phase I. All three groups were able to escalate to full dose lenalidomide 25 mg daily 21/28 days, although due to reduced accrual the phase II component was not entirely completed for groups B and C. Adverse events were as expected, including anemia, diarrhea and fatigue. Ten patients experienced grade 3–4 pneumonia. Overall response rate was 54% across all groups. PFS was 7.5 months and OS was 19.7 months. Lenalidomide can be given at full dose 25 mg daily 21/28 in patients with a CrCl \u3e 30, and can be given daily to those with CrCl \u3c 30, even when on dialysis, at doses of at least 15 mg daily

Analysis and Interpretation of Results Based on Patient-Reported Outcomes

ABSTRACT This article is part of a series of manuscripts dealing with the incorporation of patient-reported outcomes (PROs) into clinical trials. The issues dealt with in this manuscript concern the common pitfalls to avoid in statistical analysis and interpretation of PROs. Specifically, the questions addressed by this manuscript involve the analysis pitfalls with PRO data in clinical trials and how can they be avoided (e.g.,missing data, multiplicity, null results etc.). The manuscript provides key literature for existing resources and proposes new guidelines

Interpreting and Reporting Results Based on Patient-Reported Outcomes

ABSTRACT This article deals with the incorporation of patient-reported outcomes (PROs) into clinical trials and focuses on issues associated with the interpretation and reporting of PRO data. The primary focus and context of this information relates to the evidentiary support and reporting for a labeling or advertising claim of a PRO benefit for a new or approved pharmaceutical product. This manuscript focuses on issues associated with assessing clinical significance and common pitfalls to avoid in presenting results related to PROs. Specifically, the questions addressed by this manuscript involve: What are the best methods to assess clinical significance for PROs? How should investigators present PRO data most effectively in a Food and Drug Administration (FDA) application? In labeling or in a scientific publication? Guidelinesfor interpreting clinical significance of PROs and for comprehensively reporting on the methods, measures and results of clinical trials that incorporate PROs are important for clinicians, regulatory agencies, and most of all to patients. Clear specifications for considering a finding on a PRO measure, as clinically meaningful, need to be determined by instrument developers and psychometricians; they need to be reported for all clinical trials involving PRO end points. Clinical trial reports need to be comprehensive, clear, and sufficient to enable any reader to understand the methods, PRO measures, statistical analysis, and results

Impact of Zumba on Cognition and Quality of Life is Independent of APOE4 Carrier Status in Cognitively Unimpaired Older Women: A 6-Month Randomized Controlled Pilot Study

Objective: To investigate the association of a 6-month Zumba intervention with cognition and quality of life among older cognitively unimpaired apolipoprotein SMALL ELEMENT OF4 (APOE4) carrier and noncarrier women. Methods: Fifty-three women were randomly assigned to either twice-weekly Zumba group classes or maintenance of habitual exercise (control group) for 6 months. At baseline, 3, and 6 months, all participants underwent neuropsychological, physical activity, and quality-of-life assessments. Results: Overall, neuropsychological test scores and level of physical activity did not differ between intervention and control groups at any time. However, compared to the control group, quality of life was higher at 3 months, and visuospatial working memory and response inhibition improved more in the intervention group by 6 months. Apolipoprotein SMALL ELEMENT OF4 status did not affect the results. Discussion: Zumba may strengthen performance on visuospatial working memory among cognitively unimpaired older women but this needs to be tested in a larger clinical trial