Understanding Clinical Research

David Mercer, MD, PhD, FRSCS, FACS

We all want to be as healthy as possible, and in this day and age, part of that can be working to be as educated as we can be about our own healthcare decisions. The problem is that suddenly we are faced with SO MANY decisions and issues that it can be quite overwhelming. Trying to understand the results of new healthcare research is a daunting task for anyone.

If you are dealing with home nutrition, either by IV (“parenteral”) or through your gut (“enteral”), then you are already launched into a world filled with tubes, lines, pumps and fluids. It is likely that you didn’t even know this world existed prior to your current situation either as a patient or as a caregiver. Just understanding all the medication you or your loved one are on right now is plenty hard enough without then trying to keep up-to-date on what is coming in the future.

Let me start by first giving you complete permission to not worry about current medical research if you don’t want to. You are not a bad patient, nor are you being lazy or harmful to yourself or your loved one if this just seems too much for you. Let’s be honest—it can be hard enough to just find a doctor who understands your condition or is interested in treating you. It should be the role of your treatment team (doctors, nurses, dietitians, pharmacists, etc.) to keep abreast of current research and present you with the best option for your situation, or a limited number of options with an explanation to help you choose. If you have a team you trust, you may rely on them if you wish to.

However, it is also quite possible you don’t have the luxury of a well-informed team and you feel the role of learning about best current treatments is falling on you. This is much more common than you may think. Or you may just want to be truly informed about the “latest and greatest” medical research as it pertains to you, to help you feel comfortable with the choices being made about your health. If this seems like you, then perhaps I can give you just a little framework for investigating clinical trials and research.

I’m going to proceed on the assumption that you are reading about things because they pertain directly to you and your own health decisions, or to someone close to you. (If you’re studying the outcomes of clinical trials for the sake of general knowledge, well… that’s unusual, but good for you!).

Step One

I think the first step in reading about clinical trials is to get your own philosophy straight. With your eyes wide open, take stock of all the elements of your current situation—your schedules, medications, what you are happy with, what isn’t good, etc. Then close your eyes and imagine what your life would look like in a best possible situation. Keep this realistic (we would all likely choose to be 100 percent well and have NONE of this…), but also don’t be afraid to dream well beyond your present circumstances.

Why does this matter as a first step? Because if you are already very happy with how things are going, then you are unlikely to want to take much risk to gain an improvement—and clinical trials are all about benefit versus risk. If you are trying to decide whether a new intervention is a good idea for you, you have to have some idea of your risk tolerance. So, once you have this figured out for yourself, proceed to the next step.

Step Two

Where do you go for the information you need? Well, let me just say this is also super complicated. Many people are going to turn to the internet or social media as a starting point. Fair enough—but be aware that this is the WILD WEST OF MEDICAL INFORMATION. Everyone on TikTok is “an expert,” you can pretty much claim whatever you want to without responsibility, and almost none of it is verifiable.

My best advice here is to take a Ronald Reagan approach to what you hear: “trust but verify.” The wilder the claim of “success” or “breakthrough,” the more skeptical you should be. This is not to say that important information cannot be found in these sources. Indeed, major breakthroughs such as blenderized tube feeds have been driven largely by the community of patients and caregivers. Heck, my own research is based on a community-driven approach to defining quality of life in short bowel syndrome. I would just urge you to be cautious, and check with your most trusted healthcare providers before making any significant changes.

At the highest level, in a search for information one would go directly to published manuscripts using something like PubMed, an online database maintained by the National Institutes of Health (NIH) that contains millions of citations for biomedical literature. Almost no one, including the majority of physicians, is capable of doing this well. There is so much published medical research that if you look hard enough, you can find a research paper to support whatever you want to say.

To do this properly requires a broad knowledge of a field, a comprehensive search of published papers, and the knowledge of how to interpret complex data. There are organizations such as the Cochrane collaborative that do this very well, but in the home nutrition world, most of the things you care about won’t have been addressed by Cochrane, and Cochrane doesn’t always put out results in a way that is easy for the layperson to understand.

Information put out by the US Food and Drug Administration (FDA) is generally of the highest level. It’s fully vetted and verified. Pharmaceutical and device companies are highly regulated as to what they can say about their products. They cannot say anything that has not been approved by the FDA. They can certainly put a spin on their data and outcomes—after all, they are in the business of selling treatments—but at least everything they say, to the best medical probability, is generally true.

The same is not true in many industries not regulated by the FDA, and this includes many nutritional, nutraceutical and naturopathic companies. Their statements are not vetted by the FDA, and they will rarely volunteer this fact. They will talk about “study results,” but unless those results are available publicly in the form of a published manuscript, you should be very skeptical. If they have nothing to hide, then they should hide nothing. You should be able to find out where their studies are and look at them.

Terminology

As you begin to read, you will likely come across the word “significance.” This will generally refer to either “statistical significance” or “clinical significance.” If something is said to be significantly different statistically, it means two (or more) things are likely to be truly different (for example, a drug versus placebo), meaning the difference seen in the study isn’t just due to chance.

Researchers set the measure of true difference using something called a “p-value,” which is generally set at 5% and written as “p<0.05.” In effect, what they are saying is, “using the test we have, there is a 5% chance that when we say things are different, they really are not.” Somewhat arbitrarily, everyone agrees that a 5% chance of being wrong is acceptable. If the p-value is lower, say for example 0.001, this would mean there is only a 1 in 1000 chance of being “wrong.”

“Clinical significance” on the other hand is a bit easier to understand, because effectively that is determined by you the patient. Basically, it is saying that the effect of the treatment has meaning to you. This can be tricky at times, because things can be written to make a rather boring outcome look exciting.

If you saw a study that said, “This drug reduces the rate of cancer recurrence by 50%, a statistically significant finding,” you might say, “Wow, that’s really impressive!” But if the cancer in question only recurs 2 per 1000 times and now it recurs 1 per 1000 times, you might possibly conclude that isn’t clinically all that meaningful to you, perhaps when taking into account side effects, cost, length of treatment, etc. This is why I earlier made the point that you have to get your own philosophy about your clinical care figured out and understand your own risk tolerance. Because when you look at study results that might pertain to you, they are always interpreted in the context of your own situation.

Conclusion

If your team is unfamiliar with the data you are looking at, let them know the sources you are using, or even provide a copy of what you are reading. If someone is unwilling to even consider it, or quite reasonably finds it outside their expertise, they should be comfortable in sending you to an expert center where you can get help answering your questions.

Interpreting clinical data is challenging, but for some patients and caregivers, it can provide a sense of security in the knowledge that you are an active participant in advancing your own care. ■

Easy, right? Not at all. Keeping abreast of all the new developments is probably not realistic for the majority of patients. But where there are specific issues that relate to your own care, you can feel empowered to look at the data yourself. Understanding clinical data is difficult, and the best thing to do is ask questions, and discuss with your care team.

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Dr. Mercer is Professor of Surgery and Director of the Intestinal Rehabilitation Program at the University of Nebraska Medical Center in Omaha, Nebraska, and President Elect of the Oley Foundation Board of Trustees.