A Sponsor's Best Practice and Operating Principles to Manage Data Monitoring Committees.

The use of data monitoring committees (DMC) to safeguard patients' safety in clinical trials has evolved over the last decades and has become increasingly common. To ensure well-operating and high-performing DMCs, pharmaceutical companies need to establish clearly defined operational processes while continuously seeking to optimize these and adapt to the needs of drug development. Although there are health authority guidelines on establishing and managing a DMC, the perspectives and experiences of sponsors are often underrepresented.

Developing, Planning and Conducting an Interim Analysis: Lessons From the DEVOTE Cardiovascular Outcomes Trial (Trial Comparing Cardiovascular Safety of Insulin Degludec Versus Insulin Glargine in Patients With Type 2 Diabetes at High Risk of Cardiovascular Events).

Background: In 2013, a randomized, double-blind, active comparator-controlled, event-driven cardiovascular outcomes trial (DEVOTE) was initiated to compare the cardiovascular safety of insulin degludec (degludec) versus insulin glargine 100 units/mL (glargine U100) in patients with type 2 diabetes at high risk of cardiovascular events. The FDA agreed that an interim analysis could form the basis for an early regulatory approval. We report here the operational model developed to support the DEVOTE interim analysis and the results.

Semaglutide, reduction in glycated haemoglobin and the risk of diabetic retinopathy.

Aims: To evaluate diabetic retinopathy (DR) data from across the SUSTAIN clinical trial programme.

Materials And Methods: The SUSTAIN clinical trial programme evaluated the efficacy and safety of semaglutide, a glucagon-like peptide-1 analogue, for the treatment of type 2 diabetes (T2D). In SUSTAIN 6, a 2-year, pre-approval cardiovascular outcomes trial, semaglutide was associated with a significant increase in the risk of DR complications (DRC) vs placebo.

Activation of satellite cells and the regeneration of human skeletal muscle are expedited by ingestion of nonsteroidal anti-inflammatory medication.

With this study we investigated the role of nonsteroidal anti-inflammatory drugs (NSAIDs) in human skeletal muscle regeneration. Young men ingested NSAID [1200 mg/d ibuprofen (IBU)] or placebo (PLA) daily for 2 wk before and 4 wk after an electrical stimulation-induced injury to the leg extensor muscles of one leg. Muscle biopsies were collected from the vastus lateralis muscles before and after stimulation (2.

Positive muscle protein net balance and differential regulation of atrogene expression after resistance exercise and milk protein supplementation.

Purpose: Resistance exercise and amino acid availability are positive regulators of muscle protein net balance (NB). However, anabolic responses to resistance exercise and protein supplementation deserve further elucidation. The purpose was to compare intakes of whey, caseinate (both: 0.

Moderate loading of the human osteoarthritic knee joint leads to lowering of intraarticular cartilage oligomeric matrix protein.

The non-pharmacological treatment of osteoarthritis (OA) includes exercise therapy; however, little is known about the specific effect of exercise on the joint per se. The purpose of the present study was to investigate the direct effects of a load-bearing exercise upon cartilage in a single, human osteoarthritic joint determined by biochemical markers of cartilage turnover and inflammation in the synovial fluid (SF), serum and urine. Eleven subjects with OA of the knee(s), but with no other joint- or inflammatory disorders, volunteered for the study and had samples of blood, urine and synovial fluid drawn both at baseline and following 30-min one-legged knee-extension exercise.

Whey and casein labeled with L-[1-13C]leucine and muscle protein synthesis: effect of resistance exercise and protein ingestion.

Muscle protein turnover following resistance exercise and amino acid availability are relatively well described. By contrast, the beneficial effects of different sources of intact proteins in relation to exercise need further investigation. Our objective was to compare muscle anabolic responses to a single bolus intake of whey or casein after performance of heavy resistance exercise.

Exercise increases interleukin-10 levels both intraarticularly and peri-synovially in patients with knee osteoarthritis: a randomized controlled trial.

Introduction: The microdialysis method was applied to the human knee joint with osteoarthritis (OA) in order to reveal changes in biochemical markers of cartilage and inflammation, intraarticularly and in the synovium, in response to a single bout of mechanical joint loading.

Methods: Thirty-one female subjects with OA of the knee were randomized to non-exercise (NEx) or exercise (Ex) groups. Following acute resistance exercise (25 sets of 10 repetitions at 60% of 1 Repetition Maximum) or none (NEx), peripheral nerve blocks just below the inguinal ligament were applied and two microdialysis catheters were positioned in two different compartments, intraarticularly and peri-synovially.

Early osteoarthritis and microdialysis: a novel in vivo approach for measurements of biochemical markers in the perisynovium and intraarticularly.

The microdialysis technique was evaluated as a possible method to obtain local measurements of biochemical markers from knee joints with degenerative changes. Seven patients scheduled for arthroscopy of the knee due to minor to moderate degenerative changes had microdialysis catheters inserted under ultrasonographic guidance, intraarticularly and in the synovium-close tissue. Catheters were perfused at a rate of 2 μl/min for approximately 100 min with a Ringer solution containing radioactively labeled glucose, and the positions of the catheters were later visualized during arthroscopy.

Prostaglandin synthesis can be inhibited locally by infusion of NSAIDS through microdialysis catheters in human skeletal muscle.

Prostaglandins are known to be involved in the regulation of local blood flow within human skeletal muscles during exercise, and the concentration of prostaglandins increases locally and systemically in response to exercise. The systemic release of prostaglandins can be inhibited by oral intake of nonsteroidal anti-inflammatory drugs (NSAIDs). However, to study the local role of prostaglandins, the formation of prostaglandins within the tissue must be controlled.