Routine regulatory requirements for large comparative efficacy trials (CETs) to support marketing approval of monoclonal antibody (mAb) biosimilars have been the focus of extensive debate in the last few years. This review examines the mounting evidence, accumulated over the past decade, focusing on relevant literature and data published in the European Product Assessment Reports (EPARs) for the fifteen anti-TNFα biosimilars approved to date. The potential for residual uncertainties that may require resolution through CETs following comparative physico-chemical, in-vitro potency, and single dose studies in healthy subjects is examined. It is noted that structural and physicochemical differences between biosimilars and reference products are detectable using modern analytical methods at levels well below those that could impact clinical outcomes, and that in vitro potency testing is fully capable of revealing clinically relevant differences. Additionally, comparative pharmacokinetic studies in healthy participants provide a sensitive assessment of potential differences in drug exposure and immunogenicity. The added value of CETs is further questioned in the light of the fact that anti-TNFα’s display a flat dose-response relationship, meaning that unlike cell-based assays, CETs have limited sensitivity to detect potency differences. Initial concerns about extrapolating data from rheumatoid arthritis studies to support marketing approval of other indications such as inflammatory bowel disease for which not all anti-TNFα’s are effective have been alleviated by post-approval studies. Additionally, as of the end of 2024, no cases where clinical efficacy data were necessary to resolve residual quality concerns have arisen following regulatory assessment of 56 mAb biosimilars and fusion proteins. CETs add significant cost and delay to the development of biosimilars and the time is now ripe to re-examine the need for these CET’s and for further evolution in regulatory thinking.

Background: The aim of the study was to conduct a literature review within the fields of sports and orthopedic rehabilitation to evaluate the efficacy of interventions incorporating electromyographic feedback (EMG FB) training compared to same interventions without EMG FB. Methods: A systematic search of three databases (PubMed, Cochrane, and Web of Science) was conducted until February 2023, without limitation on the publication date. The search strategy adhered to the PRISMA guidelines. Inclusion criteria and data extraction protocol were established a priori. The methodological quality of the included primary studies was assessed by using the PEDro scale. Results: A total of ten randomized controlled trials (RCTs; 2 in sports and 8 in orthopedic rehabilitation) involving 397 participants were included. The outcomes were categorized into three areas: 1) muscle strength and activation, 2) pain perception, and 3) functionality and joint range of motion. The quality of these studies ranges from 5 to 8 on the PEDro scale. The findings demonstrate both significant and non-significant differences between the interventions with and without EMG FB across all categories. The calculated effect sizes vary from small to large. Discussion: This review suggests that EMG FB training can be effective to enhance muscle strength, muscle control, pain reduction, functionality, and joint range of motion. The studies provide evidence for the varying impacts of EMG FB training, demonstrating both significant and non-significant outcomes across different populations and intervention types. These differences within the findings not only highlight the potential of EMG FB, but also emphasize the need for further research to identify the conditions and populations in which EMG FB is most effective.

Soft tissue sarcoma (STS) is a rare malignancy with a high incidence. Early diagnosis can reduce the rate of amputations and increase survival, however, this is typically delayed. The diagnosis and treatment of smaller lesions have a better prognosis; nonetheless, patients present to physicians when the soft tissue mass is large with obvious signs of red flags. In addition, the symptoms of this disease are highly non-specific and overlap greatly with benign conditions, resulting in a lack of clinical suspicion and low awareness among practitioners and the general public. Thusly, it is entitled as “the loneliest cancer”. This can make an accurate diagnosis difficult, with a great proportion of misdiagnoses leading subsequent inadvertent to incomplete STS excision, affecting the overall prognosis of the disease and devastating consequences in the disease process. A timely and precise diagnosis is essential because half of people with STS progress toward quietly aggressive illness. The purpose of this review is to raise awareness of STSs so that early recognition, accurate work-up, overview of conventional treatment plans, and appropriate referral to a tumor center can be achieved, avoiding whoop situations, and improving patient outcomes. In addition, insight into the advances in immunotherapy, nanotechnology, and artificial intelligence (AI) can lead to STS diagnosis and treatment prognosis.