Standardized assessment of adverse events in rheumatology clinical trials: summary of the OMERACT 7 drug safety module update.

A presentation, demonstration, and discussion of recently developed adverse event instruments were the topics for the OMERACT 7 Drug Safety Module. The module began with a plenary introducing the needs and challenges of adverse event ascertainment. It was followed by a review of module work from previous OMERACT meetings on a prototype coding instrument (Rheumatology Common Toxicity Criteria), then a brief description of the process behind the recently developed patient self-report and investigator report adverse event instruments. These current instruments are designed for use in controlled trials although they could be used in other settings. The instruments rely primarily on patient self-reporting using a checklist, which the investigator then folds into a parallel structured but more medically sophisticated instrument. In pilot testing, this innovative dual-use system has shown reliability and acceptability, while preserving validity. A "stakeholder panel" of representatives from 8 sectors followed--patient, nurse investigator, regulator, clinician scientist, industry, OMERACT, global public health/WHO, and Cochrane Collaboration--for their perspectives on the needs, challenges, and potential ways forward for adverse event ascertainment and reporting in clinical trials. At the breakout session small focus groups participated in hands-on interactive testing of one of 3 versions of the instruments, which differ in degree of comprehensiveness. Each focus group had a participatory patient with rheumatoid arthritis. At a second plenary there was group feedback by rapporteurs and presentation of results from pilot studies of iterative testing of validity, reliability, and feasibility of the instruments. During plenary discussion a frequent suggestion for improvement was to refine the process so that event ascertainment could be done entirely using the patient instrument with minimal input from the investigator at the visit, if patient-investigator agreement was high. Most found the patient checklist attractive, particularly if the patient instrument was shown to be reliable and valid. Finally, a future research agenda was discussed.

MRI assessment of knee osteoarthritis: Knee Osteoarthritis Scoring System (KOSS)--inter-observer and intra-observer reproducibility of a compartment-based scoring system.

OBJECTIVE: To develop a scoring system for quantifying osteoarthritic changes of the knee as identified by magnetic resonance (MR) imaging, and to determine its inter- and intra-observer reproducibility, in order to monitor medical therapy in research studies. DESIGN AND PATIENTS: Two independent observers evaluated 25 consecutive MR examinations of the knee in patients with previously defined clinical symptoms and radiological signs of osteoarthritis. We acquired on a 1.5 T system: coronal and sagittal proton density- and T2-weighted dual spin echo (SE) images, sagittal three-dimensional T1-weighted gradient echo (GE) images with fat suppression, and axial dual turbo SE images with fat suppression. Images were scored for the presence of cartilaginous lesions, osteophytes, subchondral cysts, bone marrow edema, and for meniscal abnormalities. Presence and size of effusion, synovitis and Baker's cyst were recorded. All parameters were ranked on a previously defined, semiquantitative scale, reflecting increasing severity of findings. Kappa, weighted kappa and intraclass correlation coefficient (ICC) were used to determine inter- and intra-observer variability. RESULTS: Inter-observer reproducibility was good (ICC value 0.77). Inter- and intra-observer reproducibility for individual parameters was good to very good (inter-observer ICC value 0.63-0.91; intra-observer ICC value 0.76-0.96). CONCLUSION: The presented comprehensive MR scoring system for osteoarthritic changes of the knee has a good to very good inter-observer and intra-observer reproducibility. Thus the score form with its definitions can be used for standardized assessment of osteoarthritic changes to monitor medical therapy in research studies.

Incidence and cost of new onset diabetes mellitus among U.S. wait-listed and transplanted renal allograft recipients.

This study sought to determine 1) the incidence and costs of new onset diabetes mellitus (NODM) associated with maintenance immunosuppression regimens following renal transplantation and 2) whether the mode of dialysis pretransplant or the type of calcineurin inhibition used for maintenance immunosuppression affected either the incidence or cost of NODM. The study examined the United States Renal Data System's clinical and financial records from 1994 to 1998 of all adult, first, single-organ, renal transplantations in either 1996 or 1997 with adequate financial records. It used the second diagnosis of diabetes in previously nondiabetic patients to identify NODM. While NODM had an incidence of approximately 6% per year among wait-listed dialysis patients, NODM over the first 2 years post-transplant had an incidence of almost 18% and 30% among patients receiving cyclosporine and tacrolimus, respectively. By 2 years post-transplant, Medicare paid an extra $21 500 per newly diabetic patient. We estimated the cost of diabetes attributable to maintenance immunosuppression regimens to be $2025 and $3308 for each tacrolimus patient and $1137 and $1611 for each cyclosporine patient at 1 and 2 years post-transplant, respectively.