IOL Clinical Trials

One of the most commonly performed surgical procedures in the world is cataract surgery: the removal of patient’s clouded natural crystalline lens, and its replacement with a synthetic intraocular lens (IOL). The procedure has been successfully performed for more than 65 years. Over that time, many new IOLs have been developed, varying by design, material, implantation location and fixing method. Some IOLs were successful, others not; clinical evaluation, for the most part, made that distinction.

We searched clinicaltrials.gov for: ("intraocular lens" OR "implantable collamer lens" OR toric OR multifocal) NOT ("contact lens" OR "contact lenses"), and exported the entire dataset as tab-separated values, for import into and analysis within Microsoft Excel 2013. Inappropriate records (mostly related to multifocal tumors in breast cancer) were removed, and the full text of each record examined for additional details to be recorded into the spreadsheet (such as the type of evaluation performed, or the manufacturer of every IOL mentioned, where possible).

The results presented speak for themselves, but I’d like to point out a few caveats and highlights.

Caveats. It’s likely that many trials are missing from the earlier records within clinicaltrials.gov (see, “Clinicaltrials.gov: its history and why we used it”), but more recent data should be more robust. Basic data like trial Phase is missing from many records; we can only plot what’s there; some records were clearly sponsored by an IOL manufacturer, but then no information was then presented in the record regarding whose IOLs were used. Trial enrolment numbers were generally small, and outliers have on occasion skewed the data. For example, “Basic Research” trials (n=5) had the highest average number of patients enroled (at 350.6), but this was skewed by one observational study that enroled 1500 patients; without it, the average enrolment dropped to 63.25. Nevertheless, the overall average enrolment across the entire dataset analyzed was 120.6. Additionally, clinicaltrials.gov’s dataset has been expanded to include trials from before its inception: the record with the earliest start date (February 1992) was NCT00453011, which was completed in February 1998, but added to the registry in March 2007. It’s worthy to note that all such examples were funded by the US government – either by the NIH or the Department of Veterans Affairs.

Clinicaltrials.gov: its history and why we used it

This article employs data from clinicaltrials.gov, the US National Institutes of Health’s central clinical trials registry (CTR). Launched in February 2000, it was created in order to foster greater transparency from pharmaceutical companies and clinical research organizations (CROs) against a background of allegations that some companies had been hiding any record of trials that produced poor results. It is the biggest and most well-used of all CTRs; most clinical trials, if registered, are registered there. There have been historic concerns of the quality of some of the earlier records (1), and the fact that not all trials were being registered on a CTR (2), although almost all journals should now refuse to publish results from trials not registered on one (2). Despite these notable caveats, clinicaltrials.gov is the biggest and best, and so The Ophthalmologist mined that registry to try to understand the historic, and potential trends.

Highlights. It’s hard not to notice that almost two in every five trials were in Phase IV; such trials are usually post-marketing surveillance studies; here only 35 percent of them followed a single IOL on the market; 43 percent were comparisons of different IOLs. Are some of these cases of “get a product to market, and then see if it’s better than the competition in a head-to-head battle”? Perhaps, but many (42 percent) were performed by academics, hospitals and research institutes themselves. On the other hand, only nine trials were earlier than Phase III. If this were a drug, these numbers would be shocking, but as IOLs are made from biologically inert materials, most are now evolutions of well-established designs, and their placement and function are well understood, it should not be too surprising if many go straight into Phase III. Finally, Alcon’s IOLs have undergone by far the most clinical trial evaluation, reflecting their market share and range of IOLs, although in many trials, their IOLs were used as the comparator IOL in trials sponsored by other manufacturers.

Caveats. It’s likely that many trials are missing from the earlier records within clinicaltrials.gov (see sidebar, “Clinicaltrials.gov: its history and why we used it”), but more recent data should be more robust. Basic data like trial Phase is missing from many records; we can only plot what’s there; some records were clearly sponsored by an IOL manufacturer, but then no information was then presented in the record regarding whose IOLs were used. Trial enrolment numbers were generally small, and outliers have on occasion skewed the data. For example, “Basic Research” trials (n=5) had the highest average number of patients enroled (at 350.6), but this was skewed by one observational study that enroled 1500 patients; without it, the average enrolment dropped to 63.25. Nevertheless, the overall average enrolment across the entire dataset analyzed was 120.6. Additionally, clinicaltrials.gov’s dataset has been expanded to include trials from before its inception: the record with the earliest start date (February 1992) was NCT00453011, which was completed in February 1998, but added to the registry in March 2007. It’s worthy to note that all such examples were funded by the US government – either by the NIH or the Department of Veterans Affairs.

Highlights. It’s hard not to notice that almost two in every five trials were in Phase IV; such trials are usually post-marketing surveillance studies; here only 35 percent of them followed a single IOL on the market; 43 percent were comparisons of different IOLs. Are some of these cases of “get a product to market, and then see if it’s better than the competition in a head-to-head battle”? Perhaps, but many (42 percent) were performed by academics, hospitals and research institutes themselves. On the other hand, only nine trials were earlier than Phase III. If this were a drug, these numbers would be shocking, but as IOLs are made from biologically inert materials, most are now evolutions of well-established designs, and their placement and function are well understood, it should not be too surprising if many go straight into Phase III. Finally, Alcon’s IOLs have undergone by far the most clinical trial evaluation, reflecting their market share and range of IOLs, although in many trials, their IOLs were used as the comparator IOL in trials sponsored by other manufacturers.