The TREAT-NMD advisory committee for therapeutics (TACT): an innovative de-risking model to foster orphan drug development

Despite multiple publications on potential therapies for neuromuscular diseases (NMD) in cell and animal models only a handful reach clinical trials. The ability to prioritise drug development according to objective criteria is particularly critical in rare diseases with large unmet needs and a limited numbers of patients who can be enrolled into clinical trials. TREAT-NMD Advisory Committee for Therapeutics (TACT) was established to provide independent and objective guidance on the preclinical and development pathway of potential therapies (whether novel or repurposed) for NMD. We present our experience in the establishment and operation of the TACT. TACT provides a unique resource of recognized experts from multiple disciplines. The goal of each TACT review is to help the sponsor to position the candidate compound along a realistic and well-informed plan to clinical trials, and eventual registration. The reviews and subsequent recommendations are focused on generating meaningful and rigorous data that can enable clear go/no-go decisions and facilitate longer term funding or partnering opportunities. The review process thereby acts to comment on viability, de-risking the process of proceeding on a development programme. To date TACT has held 10 review meeting and reviewed 29 program applications in several rare neuromuscular diseases: Of the 29 programs reviewed, 19 were from industry and 10 were from academia; 15 were for novel compounds and 14 were for repurposed drugs; 16 were small molecules and 13 were biologics; 14 were preclinical stage applications and 15 were clinical stage applications. 3 had received Orphan drug designation from European Medicines Agency and 3 from Food and Drug Administration. A number of recurrent themes emerged over the course of the reviews and we found that applicants frequently require advice and education on issues concerned with preclinical standard operating procedures, interactions with regulatory agencies, formulation, repurposing, clinical trial design, manufacturing and ethics. Over the 5 years since its establishment TACT has amassed a body of experience that can be extrapolated to other groups of rare diseases to improve the community's chances of successfully bringing new rare disease drugs to registration and ultimately to marke

Telemedically Supported Case Management of Living-Donor Renal Transplant Recipients to Optimize Routine Evidence-Based Aftercare: A Single-Center Randomized Controlled Trial

Improving mid-term and long-term outcomes after solid organ transplantation is imperative, and requires both state-of-the-art transplant surgery and optimization of routine, evidence-based aftercare. This randomized, controlled trial assessed the effectiveness of standard aftercare versus telemedically supported case management, an innovative aftercare model, in 46 living-donor renal transplant recipients during the first posttransplant year. The model includes three components: (i) chronic care case management initiated after discharge, (ii) case management initiated in emerging acute care situations, and (iii) a telemedically equipped team comprising a transplant nurse case manager and two senior transplant physicians (nephrologist, surgeon). Analyses revealed a reduction of unplanned inpatient acute care, with considerable cost reductions, in the intervention group. The prevalence of nonadherence over the 1-year study period was 17.4% in the intervention group versus 56.5% in the standard aftercare group (p = 0.013). Only the intervention group achieved their pre-agreed levels of adherence, disease-specific quality of life, and return to employment. This comparative effectiveness study provides the basis for multicenter study testing of telemedically supported case management with the aim of optimizing posttransplant aftercare. The trial was registered with the German Clinical Trials Register (www.DRKS.de), DKRS00007634

The cumulative analgesic consumption score (CACS): evaluation of a new score to describe postsurgical analgesic consumption as a surrogate parameter for postoperative pain and invasiveness of surgical procedures

Objective To validate and evaluate the applicability of a new score to describe postsurgical analgesic consumption in urological and surgical patients across different categories of pain medications and the invasiveness of medical interventions. Materials and Methods The cumulative analgesic consumption score (CACS) was determined for two cohorts of patients split into three groups with surgeries involving clinically distinct levels of invasiveness (n = 2 x 60). Nonparametric statistical analyses were performed to determine differences between the CACS among the different groups and to assess the correlation between CACS and numeric rating scale (NRS) values for pain intensity. Results The score was determined for postoperative days 1 and 2 and revealed median scores of 0 (0-11), 3 (0-22) and 10 (6-17) for UA (urological patients from group A), UB (group B) and UC (group C), respectively, and 4 (0-20), 8 (0-38) and 17 (7-68) for SA (surgical patients from group A, SB (group B) and SC (group C), respectively. CACS enabled reliable differentiation between groups involving different levels of invasiveness (p < 0.001). CACS and peak NRS values showed variable degrees of correlation, as expressed by levels of significance ranging from p < 0.001 to p = 0.34 (NS). Conclusions The CACS is a valid and easily applicable tool to describe postsurgical analgesic consumption in urological and surgical patients. It can be used as a surrogate parameter to assess postsurgical pain and the invasiveness of surgical procedures. These aspects may be measured to compare surgical procedures, in both clinical trials and clinical practice settings