Results of real world clinical practice with anti-VEGF treatments, presented at this year’s American Society of Retina Specialists (ASRS) 2016 Annual Meeting, highlighted a considerable gap between clinicians’ day-to-day experience and the results of clinical trials used to secure marketing authorisation. The findings, from a review of 750,000 patients, possibly represent the largest such study yet conducted in the US. Presenting the findings, Dr. Thomas Ciulla MD, VP, Clinical Strategy at Ophthotech Corp (NASDAQ: OPHT), suggested that significant differences may exist between patients and regimens in a clinical trial and the patients and regimens seen in day-to-day clinical practice. The findings are likely to be familiar to many practising clinicians and echo previous studies conducted in the EU and elsewhere.
The disease status, visual acuity and injection regimen profile of patients in clinical trial studies is generally though to be significantly more homogenous than the far broader range of patients generally seen in ophthalmic clinics. Such an observation is not specific to ophthalmology but has been widely recognized and criticized across many indications in that recruitment to commercially sponsored clinical trials tend to include healthier patients not always representative of the “real world” patient. In 2014, EURETINA’s own board member, Dr. Frank Holz (University of Bonn), published a similar study assessing real-life anti-VEGF use in an observational study in Canada, France, Germany, Ireland, Italy, the Netherlands, UK and Venezuela. The primarily European-based study showed that fewer injections are administered in clinical practice than in clinical trials and continual follow-up indicated that patients had an initial improvement in visual acuity which was generally not maintained over time.
The original 2014 EU study commented that monthly intravitreal injections used in sponsored clinical trial studies are less achievable in practice as they generally create a significant treatment burden for patients, caregivers and physicians. Quarterly or PRN are generally associated with less favourable outcomes than monthly dosing, in part explaining the difference in results. Dr. Ciulla’s findings presented at ASRS used data from the Vestrum Health Retina Research Dataset which collated data from patients that had undergone a minimum of 3 months anti-VEGF injections in the first 4 months between January 2011 and July 2013. The mean age of the patients analysed was 82 years, 70% of who were treated with bevacizumab while 15% received aflibercept and a final 15% received ranibizumab. According to Dr. Ciulla, there did not appear to be any major difference in outcomes among the three treatments. Dr. Ciulla’s review indicated that real world patients tended to do worse because they received far fewer injections than the participants in clinical trials. In addition, real world patients are likely to present with more co-morbidities and other challenges than those recruited to clinical trial studies and so ultimately, the issue may reflect how random a “randomised controlled trial” is in reality. If the patients in a study represent a skewed sample of the population then results may not be extendable to the population, an issue regualators will be keen to monitor.