Patterns of anti-vascular endothelial growth factor discontinuation in neovascular age-related macular degeneration.

OBJECTIVE: To report on anti-vascular endothelial growth factor (anti-VEGF) discontinuation in neovascular age-related macular degeneration (nAMD). DESIGN: Retrospective cohort study. PARTICIPANTS: Treatment-naive nAMD patients initiating anti-VEGF injections between 2015 and 2021. METHODS: Demographics, treatment start and end dates, number of injections, treatment length, reason for discontinuation, and baseline and final data (i.e., age, best-corrected visual acuity, and central subfield thickness) were recorded. Statistical analyses using STATA 17.0 assessed differences between baseline and final values and between treatment-discontinuation subgroups. RESULTS: A total of 619 eyes of 502 treatment-naive patients (9015 injections) were included (age, 81.6 ± 8.4 years; 64.0% female). Discontinuation rate was 58.3% (361 of 619), with 310 patients discontinuing because of the lack of visual benefit (n = 152), severe comorbidity or death (n = 82), transferred (n = 33), stable off active treatment (n = 19), lack of benefit plus stable off treatment (n = 14), patient decision (n = 6), and ocular comorbidity (n = 4). Among the 309 remaining patients, 51 (16.5%) were lost to follow-up. Discontinuation occurred within the first year in 49.3% (n = 178). Visual acuity was at least maintained in all groups and improved in the following groups: severe comorbidity or death (p < 0.0001), lost to follow-up (p = 0.0003), transferred (p = 0.0004), and stable off treatment (p = 0.0053). The lack of visual benefit group had no improvement in vision regardless of treatment length. Compared with other subgroups, those stable off treatment group was younger (p = 0.0055), had better baseline vision (p = 0.0018), received more injections (p = 0.0437) over a longer time (p = 0.0034), and achieved better final vision (p < 0.0001). CONCLUSION: While there was a high discontinuation rate over 7.5 years, most were attributable to disease or treatment factors and nonmodifiable patient factors. Discontinuation frequently occurred within the first year.

Treatment discontinuation patterns of anti VEGF in retinal vein occlusion.

OBJECTIVE: The purpose of this research is to report on real-world anti-vascular endothelial growth factor (anti-VEGF) treatment patterns in retinal vein occlusions (RVO). DESIGN: Retrospective cohort study. PARTICIPANTS: Treatment-naive RVO patients initiating anti-VEGF injections between 2015 and 2021. METHODS: Medical records available until June 2022 were reviewed. Demographics, diagnosis, number of injections, treatment length, reason for discontinuation, and baseline and final data (e.g., date, age, best-corrected visual acuity [BCVA], and central subfield thickness) were recorded. Statistical analyses performed with STATA 17.0 assessed differences between baseline and final values, branch (BRVO) and central retinal vein occlusion (CRVO), and treatment-discontinuation subgroups. RESULTS: A total of 219 treatment-naive eyes were included (70.3 ± 13.2 years of age, 52.5% female), with 99 BRVOs and 120 CRVOs (2482 injections). The discontinuation rate was 76.7% (168 of 219), with 72.7% of patients (77 of 99) with BRVOs and 75.8% of patients (91 of 120) with CRVOs discontinuing injections. Reasons for discontinuation included stable off active therapy (98 eyes), severe comorbidity or death (17 eyes), switched to intraocular steroid (implant or injection) (12 eyes), lack of visual benefit (10 eyes), ocular comorbidity (5 eyes), patient decision (5 eyes), and patient transfer (5 eyes). Among the remaining 67 eyes, 16 (24%) were lost to follow-up. Reasons for discontinuation differed between BRVO and CRVO patients (p = 0.002). Eyes with CRVO presented with worse BCVA (p < 0.0001) and achieved worse final BCVA (p < 0.0001), but both groups experienced improvements (p < 0.0001). Younger age, better baseline BCVA, and a diagnosis of BRVO were independent predictors of better final visual acuity. CONCLUSION: Over 7.5 years, treatment was discontinued for three-quarters of RVOs. Stable disease was the most common reason for discontinuation, with nearly half (45%) of all RVOs in the cohort stable off active therapy. Better visual outcomes were achieved in BRVO than in CRVO, although both groups benefited from treatment.

Ontario protocol assessment level: clinical trial complexity rating tool for workload planning in oncology clinical trials.

PURPOSE: The Ontario Institute for Cancer Research supported the creation of a working group with the objective of developing a standard rating scale to evaluate clinical trial complexity and applying the scale to facilitate workload measurement for Ontario cancer research sites. METHODS: The lack of a mechanism to measure the workload involved in a clinical trials protocol was identified and confirmed by a literature review. To collect information on how Ontario sites were assessing workload, a survey was distributed and evaluated. As a result, the working group developed the Ontario Protocol Assessment Level (OPAL), a protocol complexity rating scale designed to capture the workload involved in a clinical trial. After a training workshop on the application, OPAL was evaluated by 17 Ontario cancer centers to demonstrate its reliability and consistency during a 3-month pilot study. RESULTS: Twenty-seven protocols were reviewed by multiple sites, and the majority of the sites reported OPAL score differences between 0 and 1.5. CONCLUSION: OPAL provides clinical trials departments with an objective method of quantifying clinical trials activity on the basis of study protocol complexity. With consistent application of OPAL, sites can manage staffing objectively. The working group is continuing to monitor the application of OPAL in Ontario.

Estimating per patient funding for cancer clinical trials: an Ontario based survey.

The financial implications of conducting clinical trials in oncology have not been well researched from a perspective that would facilitate the negotiation of appropriate reimbursement. A better understanding of the resources required to conduct clinical trials is central to this process. Summaries of two hypothetical clinical trials were circulated to the clinical trials departments of the nine regional cancer centres of Cancer Care Ontario (CCO), in the Province of Ontario, Canada. The centres were asked to produce itemized budgets with per patient charges detailed for each trial. Additionally, each trial was to be separately considered as if sponsored by a federally funded cooperative group, and then as if sponsored by industry. Six of the centres reported experience generating clinical trial budgets. Specific charges by the local Institutional Review or Research Ethics Boards (REB) were not included. The total of all per patient charges for the first trial ranged from 1352 dollars to 3082 dollars when considered as a cooperative group trial, and from 1700 dollars to 7217 dollars when considered as an industry sponsored trial. Similar charges for the second trial ranged from 2251 dollars to 5826 dollars and from 2251 dollars to 11,304 dollars respectively. Despite the similarities of the regional cancer centres across the province of Ontario, there were surprisingly large differences in the submitted budgets. No centre consistently produced the highest or lowest estimates. The majority of the differences appeared to be based on the range in estimates for professional support (nurse and physician), and the required radiology investigations. For centres that negotiate specific per patient funding amounts with industry, this data would suggest a need to better understand the budgeting process and its link to appropriate resource identification to ensure appropriate funding is obtained. These issues are likely not unique to oncology.

Factors affecting workload of cancer clinical trials: results of a multicenter study of the National Cancer Institute of Canada Clinical Trials Group.

PURPOSE: Increasingly, cancer treatment centers need to be able to estimate specific costs and resources associated with clinical trials. Because the time requirements of trial coordination and data collection are not well known, the Clinical Research Associates (CRA) Committee of the National Cancer Institute of Canada Clinical Trials Group carried out a multicenter study to measure trials' task times and evaluate the effects of certain factors. METHODS: A data collection instrument was designed and validated before its implementation in the study. Eighty-three CRAs from 24 cancer treatment institutions across Canada collected timing observations of 41 tasks (156 subtasks). Information from all stages of trials activity (protocol management, eligibility and entry, treatment, and follow-up and final stage) was obtained, from initial negotiations to follow-up after study closure. RESULTS: After controlling for stage, phase and sponsor were found to be significant independent factors. Analysis within the stages showed similar patterns. New drug inclusion as a factor was confounded with phase. Industry-sponsored studies had significantly higher overall mean times than did local and cooperative group studies. Early-phase studies required more time than did phase III trials. External sponsorship of any kind increased CRA time more than that necessary for locally coordinated studies, except during the protocol management stage. The burden of a phase I study increased to greater than average once underway and accruing patients. CONCLUSION: Our data demonstrated that sponsor and study phase are important factors to be taken into consideration when estimating clinical trial costs and resource use.