Exploring Differences in Screening and Enrollment Metrics in Orthopaedic Clinical Trials.

The success of any clinical trial relies heavily on patient recruitment and retention. The purpose of this study was to review screening and enrollment metrics for orthopaedic clinical trials, comparing different patient populations to determine common challenges to recruitment and differences in rates of enrollment. Screening logs and study trackers were manually reviewed for four clinical trials at a single academic institution and included randomized controlled trials (RCTs) and an observational study. Data extracted from these documents included the number of patients screened, number excluded and reasons for exclusion, number enrolled, number of withdrawn and reason. Of the four trials reviewed, the point-of-care diagnostic test had the highest number of patients excluded and the lowest patient refusal rate. Refusal rates were highest in the venous thromboembolism prophylaxis study and enrollment rates were the lowest in the RCT of drug treatments and the highest rate in the observational study. The success of the trial relies on the ability to recruit patients and factors need to be considered when recruiting participants including sample size requirements and inclusion and exclusion criteria. These data provide some insights into the patient recruitment experience at our institution with different patient populations and study types, highlighting key points to be aware of when planning for an orthopaedic clinical trial.

Orthopaedic clinical research: building a team that lasts.

Medical progress, including in the orthopaedic surgery field, depends on the interaction and collaboration between: physicians, with their expertise on the clinical setting; scientists, with their expertise on the research setting; and professionals who are skilled in both settings (clinical scientists). This leads to the need to develop research approaches which involves people who are committed and support the process, strategic planning, and a cohesive team that can execute the tasks. All these interactions must be supported financially in order to maintain the long-term viability of such team.Time management is crucial for the clinical research team. To ensure success, the research team must be flexible in order to adapt to dynamic clinical and surgical schedules. It is especially important that surgeons have regular, dedicated quality research time to maintain a consistent interaction with the team.Building a successful and productive orthopaedic clinical research programme involves many challenges in creating proper leadership, obtaining funding, setting proper resources, establishing necessary training, and providing guidance and insight around the importance of each role that every member plays on the team. Cite this article: EFORT Open Rev 2021;6:245-251. DOI: 10.1302/2058-5241.6.200058.

Outcomes of Intraoperative OCT-Assisted Epiretinal Membrane Surgery from the PIONEER Study.

PURPOSE: To assess the retinal architecture changes which occur during epiretinal membrane (ERM) surgery, utilizing intraoperative optical coherence tomography (iOCT). DESIGN: Prospective multi-surgeon single center study. SUBJECTS/PARTICIPANTS: Subjects from the PIONEER iOCT study who underwent surgical intervention for management of ERM. METHODS: All subjects underwent vitrectomy with ERM peeling with optional internal limiting membrane (ILM) peeling. Preoperative, intraoperative, and postoperative quantitative and qualitative OCT assessments were performed. Clinical characteristics including visual acuity outcomes, central subfield thickness and complications including ERM recurrence and need for reoperation were assessed at 3, 6 and 12 months following surgery for membrane peeling, as available. MAIN OUTCOME MEASURES: Visual acuity outcomes, anatomic outcomes and complications including ERM recurrence. Microarchitectural alterations (i.e. retinal layer changes) following membrane peeling visualized with iOCT. RESULTS: Seventy-six were identified and included in this analysis of clinical outcomes and quantitative OCT assessment. Twenty-four eyes were excluded due to insufficient intraoperative OCT quality for quantitative assessment. The mean preoperative VA measured 20/63. The mean postoperative VA at 3 months was 20/41 (p<0.0001), at 6 months measured 20/36 (p < 0.0001), and at 12 months measured 20/33 (p < 0.0001). Preoperative mean central subfield thickness (CST) was 426 microns. At 3 months, the mean CST improved to 377 microns (p < 0.0001). The 6-month postoperative CST was 367 microns (p < 0.0001) and the 12-month postoperative CST measured 359 microns (p < 0.0001). Immediately following membrane peeling, the distance between the retinal pigment epithelium and the ellipsoid zone as well as the distance between the retinal pigment epithelium and the cone outer segment tips/interdigitation zone significantly increased (p < 0.001). iOCT identified occult residual membranes in 12% of cases and confirmed complete membrane peeling contrary to surgeon impression in 9% of cases. Reoperation was required for recurrent ERM in 1% of eyes. CONCLUSIONS: iOCT-assisted ERM peeling resulted in significant improvement in visual acuity, reduction in macular thickness, and low recurrence rate. Additional research is needed with randomized clinical trials to better define the comparative success rates of image-guided ERM surgery to standard surgical visualization techniques.

A Prospective Randomized Comparative Dosing Trial of Ranibizumab In Bevacizumab-Resistant Diabetic Macular Edema: The REACT Study.

PURPOSE: To assess the efficacy of ranibizumab for persistent diabetic macular edema (DME) previously treated with bevacizumab and compare monthly vs treat-and-extend (TAE) dosing. DESIGN: 12-month, open-label, prospective randomized comparative dosing study. PARTICIPANTS: 27 participants with persistent foveal-involving DME recently treated with bevacizumab. METHODS: All subjects were to receive three initial monthly 0.3 mg ranibizumab injections before randomization to monthly (n=15) or TAE (n=12) injection protocols over 12 months. Treatment interval was extended by two weeks up to a maximum interval of 12 weeks in the TAE group if central subfield thickness (CST) was ≤ 300 µm or complete absence of intraretinal or subretinal fluid on the macular cube was observed. Follow-up interval was decreased by 2 weeks if CST increased above 300 µm with associated intraretinal and/or subretinal fluid. MAIN OUTCOME MEASURES: Change in Early Treatment of Diabetic Retinopathy Study (ETDRS) best corrected visual acuity (BCVA), CST, adverse events. RESULTS: Prior to study enrollment, subjects received an average of 8.6 bevacizumab injections. At month 12, mean ETDRS BCVA improved by + 5.3 letters (p<0.05) and mean CST decreased by -99.6 µm (p<0.01) in all patients. At study exit, 18.5 % of subjects gained ≥ 3 lines of vision and 3.7% of subjects lost ≥ 3 lines. Patients treated via the TAE protocol gained +8.4 letters and decreased CST by -120.2 µm whereas those treated by monthly injection gained +2.7 letters and decreased CST by -83.1 µm at month 12. CONCLUSIONS: Following conversion to ranibizumab in eyes with persistent DME refractory to bevacizumab, significant functional and anatomic improvements were noted. Visual and anatomical outcomes were similar in TAE and monthly treatment protocols.