With the big ADA conference underway this weekend, we’re being bombarded with headlines about diabetes clinical trials — first and foremost all the news about the conflicting results of the ADVANCE and ACCORD studies. If you read the details, you’ll find a lot of stuff about randomized, controlled, double-blind, yada, yada, yada studies. Whoa, that’s a lot of jargon to digest. And what does it all mean?
Since clinical trials are so vital to advancements in diabetes treatment, it seemed like a good time to revisit the “research primer” that Dr. Jackson and I complied for our book. (Research for Dummies? I learned a lot.) Know your jargon and all the announcements will make a lot more sense:
Prospective means that the studies were planned before the occurrence of the events that they measured, compared to retrospective studies, which are conducted to “look backward” and explore events that have already occurred.
Controlled means that there is second group of subjects, similar to those who were treated, but who didn’t receive the primary treatment. You need them so you can compare the results of the two groups to better understand what the effects of the treatment were. For instance, if you followed a group of people treated with a pink pill for ten years, you might find that they gained an average of ten pounds. Is this weight gain a direct effect of the pink pill? If you also followed a control group, that didn’t receive the pink pill, you might find that their average weight gain was 20 pounds. Now your conclusion might be very different; it seems that the pink pill might help people keep their weight down. Of course, for the control comparison to be most useful, the groups must be comparable in all risk factors that are important to the topic being studied. For example, here you would want to know that the same number of people in each group live next to a donut shop, or that equal numbers were active members of fitness centers.
Randomizing study groups means that a computer program randomly assigns individuals to either the treatment group, or the control group. This compensates for any unknown risk factors that you might not have recognized. Perhaps people with blue eyes are more likely to gain weight than people with brown eyes, and since you are attracted to people with blue eyes, you might unknowingly assign more of them to the study group than the control group. Randomizing eliminates this possibility.
Blinding (or sometimes called masking) adds another layer of protection from biased results. The idea is that research subjects do not actually know if they are receiving the treatment, or if they are part of the control group. In our example above, the control group also takes a pink-colored pill, but one that is a placebo, i.e. contains no active ingredient. In what is called a double-blind study, even the researchers don’t know who’s receiving the real treatment, until the end of the trial, when the “code” is broken, and the data is analyzed. Mystery might just make the whole thing more fun!
Because it is difficult to perform a large-scale, long-duration, prospective, randomized, controlled, double-blinded clinical trial, lots of research uses less rigorous approaches. This is one of the reasons why news reports of research seem confusing and contradictory; does coffee hurt your health or help it? And what about alcohol? Many studies suggest that moderate alcohol consumption may decrease heart problems. But no one really knows, and it is unlikely that we will soon be able to identify large numbers of people in their ‘40s or ‘50s who don’t drink, and then randomly assign some to moderate alcohol consumption for the next five to ten years, and others to total abstinence. Blinding the study would be even more difficult: how could some people drink alcohol without knowing it? You get the idea; some questions are difficult to answer with certainty through clinical studies.
But regarding the impact of A1c, blood pressure, lipids, microalbumin, and eye exams, the answers are much more clear. There have been large-scale, long-duration, prospective, randomized, controlled double-blinded (with some exceptions where blinding was difficult) trials that confirmed the powerful effects of controlling these factors. Moreover, there weren’t just one or two or even three studies in each area, but multiple studies, all supporting the conclusion that keeping these five factors in a safe range will ensure that you have reduced or even eliminated your chance of developing diabetes complications.