Monday, May 16, 2011

The Importance of Clinical Trials

Bloodletting as a medical treatment has been around for over 2000 years. The ancients believed that the human body was controlled by and contained 4 “humors”. These were black and yellow bile, phlegm and blood. While we still do look at the colour and consistency of some of these “humors” to help diagnose conditions (think of your runny nose during a cold vs. during an allergy attack), we do not depend on Humorism as a method of medical practice.

For the 2000 years that bloodletting was common, sometimes it worked, most times it didn’t. The physicians of the day believed that relieving an ailing body of some or a lot of its sanguine humor(blood) would cure the patient of whatever ailed him. It wasn’t until the 1800s, when a French doctor conducted what is considered the first clinical trial, that the practice of bloodletting as a cure or treatment was disproved.

To be fair, for a few people who have an iron overload because of a genetic condition, bloodletting allows them to live normal lives. Leeches, used for years as a bloodletting tool, are used in some surgeries to prevent clotting of some tiny blood vessels. So there is a use for bloodletting, in controlled and very well defined situations.

Before there were clinical trials, belief and experience were the bases of medical treatment. Let’s look at this in the context of multiple sclerosis:

- We know that the natural history of MS is one of relapse and remission with and without treatment. That’s the way this disease works for the majority of us. (In my case, my first attack was treated with IV steroids, then pill form for two weeks – I eventually gained back about 97% of what the initial attack caused me to temporarily lose.)

- People seek help from their doctor when they’re at their worst. We don’t go to the doc for a tingly finger, but if the whole side of our body is numb, we go in pretty fast, even though both may be symptoms of a relapse. Sometimes we aren’t even aware we had a relapse(or attack) until months or years later when we recall “that time my finger was asleep for three days” - this is precisely what happened to me; two months before going to the doctor because of increasing weakness on my right side, I had a tingly finger for three days, but I didn’t recall it until two years later when wondering if I had earlier symptoms of MS than January 1998.

- People, both patients and doctors, have a strong sense of hope and look for positive results with treatment.

- Placebo response – this is such an important topic, I will be spending an entire blog post on it.

- The power of anecdotes is amazingly strong and it is the lowest level of evidence. Again, I’ll have to spend an entire blog post on this one.

One of the many early treatments for MS was strychnine (!) After all, in small doses, it was a stimulant; anyone with MS fatigue knows what a stimulant can help us accomplish. As well, application of severe and prolonged cold wraps then blasting with cold water (that’ll get me up and moving for sure, if only to get away from the treatment), inducing fevers to rid the body of toxins , other poisons like arsenic and mercury, and electrical stimulation were all treatments for MS at some point in time. After receiving any or all of these treatments, some people with MS got better and some didn’t. I would like to suggest that those who got better did so in spite of their treatment. That’s the natural history of MS. (Remember the adage for the common cold? A cold will last 7 days if you do nothing, a week if you treat it.)
Doctors, in general, want to help their patients. Both are invested in the patient’s improving condition. We all (docs and patients) hope that we’ll get over our cold if we go to bed with chicken soup and apple juice and acetaminophen for aches. We all hope a round of steroids will improve our current attack of MS or that by taking a long term disease modifying drug the attack won’t last as long or be as damaging. If there is some improvement we, both docs and patients attribute it to the course of treatment (and not the alignment of the planets that week).

The jury is still out on chicken soup as a cure or treatment for the common cold (is it the warm steam from the soup that helps clear your sinuses, is there some nutritional factor in the soup needed to fight a cold, would drinking any hot beverage do the same thing by keeping us hydrated), but some clinical trials have been undertaken to answer these questions. The jury is in on the current batch of disease modifying drugs for MS, though. Years of research and clinical trials have been undertaken that show these drugs are effective. Yes, some people don’t do well on these DMDs, others can’t or won’t tolerate the side effects or taking a needle every day or a couple of times a week or even once a week (MS patient compliance with treatment is a big topic for docs and researchers in this field). Some current research is looking at an individual’s genetic make-up and blood chemistry response to a DMD to find out who is most likely to benefit from a certain treatment (I should know, as they continue to receive samples of my blood for this reason). My point is that we wouldn’t be at this stage in the treatment of MS without clinical trials. 20 years ago, there was nothing to offer an MS patient except hope that something would be developed or discovered soon.

Hopefully you have a better understanding of the importance of clinical trials. Our limited and biased beliefs and experiences simply can't substitute for clinical trials. They are part of what we call evidence based medicine or evidence based practice. There are levels of evidence of which I mentioned anecdotal earlier. It is the lowest level of evidence. It has not been tested or studied enough. Ethics, cost, design of studies, and the number of participants are all factors that contribute to determining the level of evidence. And so, another topic in which to delve in greater detail in the near future.

PS: Much of this blog post was inspired by the lecture by Dr. T.J. Murray earlier this week. So a tip of the hat to my good doctor.

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