A survey among retinal specialists in the UK and Ireland has indicated that the real world outcome for patients with vitreomacular traction (VMT) and full thickness macular hole (FTMH), when treated with ocriplasmin, is significantly different to the results presented in clinical trials. A retrospective survey among members of the British and Eire Association of VitreoRetinal Surgeons (BEAVRS) found “both a higher incidence of adverse events after ocriplasmin, and lower success rates for macular hole closure, than described in the phase 3 trials”. The BEAVRS study was undertaken due to a number of reports of adverse events, including reports in the literature of “previously unreported side effects, such as enlargement of the macular hole, zonular instability, and localised non-rhegmatogenous retinal detachment”. The authors of the BEAVRS study have called for increased numbers of real world studies to further clarify the safety and efficacy of ocriplasmin.
The survey results, published by Nature’s journal, Eye (2017, 31, 107–112), were prepared and analyzed by clinicians at Bristol Eye Hospital, Gartnavel Hospital, Glasgow, St. Thomas’ Hospital, London, the Maidstone Hospital, Kent, and the Sunderland Eye Infirmary. Data was collected from survey respondents who were members of BEAVRS that had used ocriplasmin and had been contacted by email. Approximately 40% of the members asked responded to the survey and provided data on the cases treated with ocriplasmin up to October 2014.
The results from the BEAVRS members (covering 241 eyes) was then compared to the results published in the “Microplasmin for Intravitreous Injection-Traction Release without Surgical Treatment” (MIVI TRUST) pivotal trials (TG-MV-006 and TG-MV-007), reported in August 2012. Analysis of the two studies showed that for the BEAVRS and MIVI-TRUST, respectively, the trial closure rates for small FTMHs were 42.1% and 58.3% (P=0.09) and for medium FTMH was 12.7% and 36.7% (P=0.01). The respective results in terms of VMT release rates were similar at 34.1% and 37.4%. One of the most significant differences was that seen in respect of retinal detachment, occurring in 3.3% of the BEAVRS cohort compared with 0.4% in MIVI TRUST. In addition, reduction in visual acuity to <6/60 was observed in 5.8% of the BEAVRS cohort and 0.6% in MIVI TRUST.
While the absolute numbers assessed in both studies were different, the trend clearly indicates a disconnect between the real world outcomes observed by clinicians in the treatment of patients attending clinic, and the results published in the MIVI-TRUST trial. Such differences between academic led real-world clinical studies, and those reported by the pharmaceutical industry, are not new. Several studies and analyses, aired widely in the professional literature and further afield, have consistently drawn attention to initiatives to improve the design and quality of data delivered to clinicians for use in medical decision making. The regulators in the US, UK, EU, and globally, have a significant role to play in adjudicating such studies. The current BEAVRS study does not highlight any specific clinical design or data quality issues to explain the differences between the two data sets and, as the authors comment, more real world studies will be required to tease out any anomalies. Availability of all trial data submitted to the EMA may additionally contribute to a fair and transparent assessment to assist in reconciling both data sets.