Every day, the Digital Optical Coherence Tomography Reading Center (DOCTR) at the Cole Eye Institute receives complaints from investigators about our interpretation of the inclusion/exclusion criteria or whether there was CNV activity on an OCT. What invariably follows is a back-and-forth between the site and DOCTR about why one side is right or wrong. Like barristers debating their closing arguments in front of the 9 justices of the Supreme Court of the United States (SCOTUS), the litigants explain why this is really leakage and not staining, why this represents CNV not atrophy, or whether there is fluid in the fovea or not. So, who is usually right? Who wins the argument? In most cases, it is the reading center, but that is not always the case.
The 2010 SCOTUS decision in Citizens United v. Federal Election Commission1 was controversial and is still a source of much debate. The court ruled that political spending is protected under the First Amendment, so corporations and unions could spend unlimited amounts of money on political activities, if it was done independently of a party or candidate. According to the ruling, as far as free speech is concerned, corporations have the same rights as individual citizens. Opponents argue that the ruling is a slippery slope toward the domination of special interests over elections, and even the potential for corporations to seek other similar individual rights, such as the right to vote.
Much like SCOTUS decisions can be hotly debated, so can the decisions from a reading center, but in general the disparity lies in the fact that the sites often look at only 1 or 2 images, whereas the reading center looks at all the images. Another common difference lies in the art of ophthalmology where two people looking at the same thing can have very different opinions. Contrary to popular belief, the reading center does not have an agenda, it simply follows strict protocols. So, when a study excludes patients with an epiretinal membrane, and we find one, it doesn’t matter if we consider it to be a minimal one that is not affecting vision — the patient is excluded. As retina specialists, we understand that the ERM we found is irrelevant to the study. However, we are tasked to follow the protocol. Sites often do vehemently disagree with our interpretation. In this issue, we discuss reasons between the grading of images at a reading center and a clinical site and what these differences might mean when interpreting trial results in practice.
Too often, we generalize clinical trial results to fit the patient we have in front of us, not understanding key differences. For example, the phase 2 Fovista study enrolled only patients with classic containing lesions and the results were significant. The phase 3 study widened the inclusion criteria to include patients with subretinal hyper-reflective material on OCT. Subretinal hyper-reflective material is seen in all lesion compositions, so allowing them in the study changed the inclusion criteria between the phase 2 and 3 trials. Would we have done the same in clinical practice? We will never know, because the phase 3 trial failed.
- Citizens United v. Federal Election Commission. https://www.supremecourt.gov/opinions/09pdf/08-205.pdf