Report From the 2022 Mary Tyler Moore Vision Initiative Diabetic Retinal Disease Clinical Endpoints Workshop.

The Mary Tyler Moore Vision Initiative Diabetic Retinal Disease (DRD) Clinical Endpoints Workshop was held on October 22, 2022 to accelerate progress toward establishment of useful clinical and research endpoints and development of new therapeutics that have important relevance across the full spectrum of DRD pathology. More than 90 patient representatives, clinicians, scientists, funding and regulatory agencies, diagnostic, therapeutic and biotech industry representatives discussed the needs for new diagnostic and therapeutic approaches to prevent and restore retinal neurovascular unit integrity. Phase I of the MTM Vision Initiative plans, notably updating the DRD staging system and severity scale, establishing a human ocular biorepository and resource, and clinical endpoints and biomarker development and validation, was emphasized.

The future is old - Patients with topical ocular hypotensive treatment in the Nordic region between 2008 and 2017 with projections for 2040.

PURPOSE: The primary objective was to evaluate prescribing trends for topical ocular hypotensive treatment in the Nordic region during the last decade and, by population projections, estimate the glaucoma burden in 2040. A secondary objective was to analyse national variations in prescription patterns across the Nordic region. METHODS: A retrospective analysis of national pharmacy data between 2008 and 2017 on the dispensation of topical ocular hypotensive treatment in the Nordic region was performed. Predictions of the glaucoma burden in 2040 were calculated from official population projections. RESULTS: The total number of patients with ocular hypotensive treatment in the Nordic region increased from 346 000 to 418 000 (21%) between 2008 and 2017. The number of patients with ocular hypotensive treatment in the age group of 50 years and older increased from 3.6% to 3.9%. The daily defined dose (DDD) per patient and day during the study period increased from 1.22 to 1.26. Adjusted for beta-blocker combinations, the same value increased from 1.49 to 1.67. Across the Nordic countries, Finland had almost twice as many DDD per patient and day in 2017 (2.1) compared with Iceland (1.1). Between 2008 and 2017, the annual treatment cost for ocular hypotensive treatment in the Nordic region decreased from 96 million to 87 million Euro (-9%). In 2040, the number of patients with ocular hypotensive treatment in the Nordic region is estimated to 633 000 individuals (+51% compared with 2017). CONCLUSIONS: The study revealed an increased use of glaucoma medications in the Nordic region the last decade. This was mainly caused by an increased number of patients with ocular hypotensive treatment, but also because of a more intensive treatment. Marked national differences were detected. Due to the introduction of generic medications, the total cost for ocular hypotensive treatment did however decrease during the last decade. In 2040, the current number of individuals with ocular hypotensive treatment is estimated to have increased with an additional 50% due to a growing number of ageing individuals. This will lead to higher costs, not only for medications but also for diagnosing, monitoring and other aspects of glaucoma care.

ISOPT Clinical Hot Topic Panel Discussion on Uveitis and Inflammation.

For this "hot topic" session in uveitis we selected first and foremost an issue that puts our clinical work and research in "holding pattern." The issue is our method of evaluating the severity of uveitis. We posed the following questions to our esteemed panelists: 1.The relative significance of cells vs. flare in following uveitis patients 2.Cells/flare measurements 3.A glance into the future and the relevance of endpoints in clinical studies and their methodologies While there are different opinions in managing and monitoring uveitis patients, there seems to be an agreement on the high need of improving objective mode/s of reliably measuring both cells and flare and better understand their significance.

Growth Hormone Research Society perspective on biomarkers of GH action in children and adults.

OBJECTIVE: The Growth Hormone Research Society (GRS) convened a Workshop in 2017 to evaluate clinical endpoints, surrogate endpoints and biomarkers during GH treatment of children and adults and in patients with acromegaly. PARTICIPANTS: GRS invited 34 international experts including clinicians, basic scientists, a regulatory scientist and physicians from the pharmaceutical industry. EVIDENCE: Current literature was reviewed and expert opinion was utilized to establish the state of the art and identify current gaps and unmet needs. CONSENSUS PROCESS: Following plenary presentations, breakout groups discussed questions framed by the planning committee. The attendees re-convened after each breakout session to share the group reports. A writing team compiled the breakout session reports into a document that was subsequently discussed and revised by participants. This was edited further and circulated for final review after the meeting. Participants from pharmaceutical companies were not part of the writing process. CONCLUSIONS: The clinical endpoint in paediatric GH treatment is adult height with height velocity as a surrogate endpoint. Increased life expectancy is the ideal but unfeasible clinical endpoint of GH treatment in adult GH-deficient patients (GHDA) and in patients with acromegaly. The pragmatic clinical endpoints in GHDA include normalization of body composition and quality of life, whereas symptom relief and reversal of comorbidities are used in acromegaly. Serum IGF-I is widely used as a biomarker, even though it correlates weakly with clinical endpoints in GH treatment, whereas in acromegaly, normalization of IGF-I may be related to improvement in mortality. There is an unmet need for novel biomarkers that capture the pleiotropic actions of GH in relation to GH treatment and in patients with acromegaly.

Biomarkers and Surrogate Endpoints in Drug Development: A European Regulatory View.

Purpose: To give a European regulatory overview of the requirements on and the use of biomarkers or surrogate endpoints in the development of drugs for ocular disease. Methods: Definitions, methods to validate new markers, and circumstances where surrogate endpoints can be appropriate are summarized. Results: The key endpoints that have been used in registration studies so far are based on visual acuity, signs, and symptoms, or on surrogate endpoints. In some ocular conditions, established outcome measures such as those based on visual acuity or visual field are not feasible (as with slowly progressing diseases), or lack relevance (e.g., when central visual acuity may be preserved even though the patient is legally blind owing to a severely restricted visual field, or vice versa). Conclusions: There are several ocular conditions for which there is an unmet medical need. In some of these conditions, surrogate endpoints as well as new clinical endpoints are needed to help speed up patient access to new medicines. Interaction with European regulators through the pathway specific for the development of biomarkers or novel methods is encouraged.

Postoperative pain management on surgical wards--do quality assurance strategies result in long-term effects on staff member attitudes and clinical outcomes?

Postoperative pain management (POPM) remains suboptimal on surgical wards in many countries despite the availability of effective analgesics, new technologies for drug administration, and clinical practice guidelines for pain management. The aim of the present study was to assess remaining long-term effects on pain management routines, patient experiences, and staff member attitudes in surgical wards more than 3 years after introduction of a quality assurance program for POPM and compare the findings to those of an organization where a corresponding systematic, entire hospital, quality assurance program had not been completed. A descriptive and comparative design, based on survey data from both patients (N = 110) and staff members (N = 51) on urologic surgery wards, was used. Significant (p <.05 to p <.0002) overall relationships were observed for identified shortages in pain management routines (lack of preoperative information, inadequate preoperative discussions on pain management, wait for pain killer) and reported experience of pain, nausea, or vomiting in the postoperative period. The quality assurance program, anesthesia-based pain services using a nurse-based anesthesiologist-supervised model, resulted in more adequate pain management routines, better patient satisfaction with POPM, and increased confidence in pain management among nurses on the surgical wards. On the basis of the present study it may be concluded that more than 3 years after the introduction of a quality assurance program for POPM in surgical wards, the pain management routines, patient experiences, and staff member attitudes have remained markedly improved and in accordance with the aims of accepted clinical practice guidelines for surgical pain management.