The trials and triumphs of eye health research
In recent years there have been several positive developments for people living with wet age-related macular degeneration (AMD). Given the transition to a new standard of care with biological treatments and, more recently, the promise of gene therapy, it is easy to forget that just over a decade ago, this eye condition was a disorder that quickly led to blindness. Now, modern treatments typically limit the loss of vision over five years to one to two lines of the eye test letter chart, with many patients maintaining vision sufficient to hold a driving licence.
Patient benefit and the search for new treatments is of primary importance and researchers will continue to seek ways of improving lives. However, since anti VEGF biologicals entered clinical practice in 2007, it can’t be ignored that the high cost of drugs and life-time need for monitoring and treatment when required has imposed a huge burden on all health care services.
The NIHR-funded IVAN trial was designed to test whether a cheap, unlicensed drug Avastin was as successful in treating wet AMD as a licensed one (Lucentis) and whether only treating active disease was as good as treating every month, regardless of disease activity. The cheap drug is licensed to treat cancer; and the dose is large compared to the amount needed to treat wet AMD. One dose of a cancer treatment can be converted into many small doses for injection into the eye to treat wet AMD. Clearly, both the comparisons tested in IVAN had important implications for the NHS – directly, due to the price of the drug and indirectly if fewer treatments could be shown to be as good as more treatments.
The IVAN trial showed clearly that the cheaper drug was as good as the expensive drug in improving and maintaining eyesight. Unfortunately, since these results have been published, there has been confusion and debate over guidelines regarding licensed and unlicensed drugs and NHS doctors and commissioners have been advised they could only use licensed treatments when these were available. So, despite Avastin being cheaper, until now it has not been in general use in the UK.
Last year, a court ruling upheld the principle that commissioners of health care and doctors may offer Avastin to patients instead of Lucentis or other more recently licensed treatments. Evidence from the IVAN trial has been crucial in the court deciding that all these treatments are equally effective. This ruling has enormous implications for the NHS – it represents an opportunity to invest savings from the NHS drug budget into resources needed to ensure prompt diagnosis, review and treatment over the course of the disease. This opportunity illustrates the value of the far-sighted NIHR investment in research on how to optimise detection of the disease as early as possible and make the process of monitoring patients for active disease and the need for additional treatment as convenient and efficient as possible.
But the evidence to support the court ruling isn’t the only important consequence of the IVAN trial….
We have just completed long-term follow-up of the people who took part, five to seven years after we stopped checking their vision in the trial. We were successful in collecting information for almost all participants who exited, including those who had sadly died by the time we started the long-term follow-up (23%). Several important findings have emerged:
- At the time of data collection, 60% of surviving patients were continuing to benefit from treatment in the NHS. This proportion is much higher than has been reported for other similar studies, even for shorter durations of follow-up.
- Contrary to early assumptions, the need for treatment continues. The NHS has been providing medical care as required up to seven years after starting treatment, with the frequency of treatment remaining much the same over time.
- However, consistent with long-term follow-up of other trials, patients lose vision slowly but steadily with time. As described above, five years after starting treatment, patients still receiving treatment were able to read two fewer lines of the visual acuity chart (having gained one line with treatment during the two-year duration of the trial). It is important to remember that compared to not having been treated, this still represents a “gain” of six to eight lines of the chart.
The long-term information which we have been able to collect with additional NIHR funding, combined with the original IVAN dataset, is immensely valuable both to doctors and commissioners in the UK but also beyond. Since the trial ended, we have had several requests from academics and industry for the IVAN dataset and associated retinal images, even though imaging technology has advanced hugely over the 10 years – and, at the time of writing, we are negotiating two new industry collaborations.
The views and opinions expressed in this blog are those of the authors and do not necessarily reflect those of the NIHR or the Department of Health and Social Care.