What I am talking about is examining outcomes. I did a post a couple of years ago here, where I use the following quote from a Pharma scientist:
"The vast majority of drugs - more than 90 per cent - only work in 30 or 50 per cent of the people," Dr Roses said. "I wouldn't say that most drugs don't work. I would say that most drugs work in 30 to 50 per cent of people. Drugs out there on the market work, but they don't work in everybody."Here is that word "work" again. What does this mean? well, let's take such common condition as heart disease. What does heart disease do to a person? Well, it can do many things, including give him/her such symptoms as a chest pain, shortness of breath, dizziness and palpitations, to name a few. These symptoms may have at least two sets of implications: 1) they are bothersome to the individual, and in this way may impair his/her enjoyment of life, and 2) they may signal either a present or a future risk of a heart attack. Why are heart attacks important? Well, they are important because one may kill the person who is having it, or one (or several) may weaken the heart to the point of a substantial disability and thus a deterioration in the quality of life. So, there certainly seems to be a good rationale to prevent heart disease either from happening in the first place or from at least worsening when it's already established.
Now, what's available to us to prevent heart disease? Well, some think that lowering one's cholesterol is a good thing. OK, let's go with that. What is the sign that the statins (cholesterol-lowering drugs) "work"? What would it look like if it was about lowering the cholesterol? Say, your total cholesterol is 240. You go on a statin and in 6 months your total cholesterol is 238. Your cholesterol was lowered, it worked! Well, yes, but if you are asking what this 2-point drop really accomplishes, you are beginning to understand the meaning of "work." So, just intuitively we can say that there needs to be a certain, perhaps "clinically significant," drop in the total cholesterol in order for us to say that the drug "worked."
Great! Now we are sidling up to the real issue: What constitutes a "clinically significant" drop in cholesterol? Is it some arbitrary number that looks high enough? Probably not. How about some drop that correlates to a drop in the risk of the actual condition we are trying to impact, heart disease? Say, a 40-point drop, or getting to below 200, may be the right threshold for the "works" judgment. Ah, but there is yet another question to ask: How often does this type of a drop lead to a reduction in heart disease? Is it always (not likely), or is it the majority of the time (rarely) or at least some of the time (most likely in clinical medicine)? And what portion of that time do we consider satisfactory -- 60%? 40%? 20%? 2%?
Let me bring just one more layer into this discussion. Many people walk with heart disease and don't know that they have it. Some of these people are destined to have a heart attack and/or die from it. Many others are likely to die from something else before they ever experience any symptoms or signs of their heart disease. This raises the question of whether the statins' ability to reduce cholesterol and hence reduce the risk of heart disease is enough to say that the drugs "work." Perhaps "work" means that by lowering cholesterol (say in the majority of those who take it) they reduce the risk of hear disease in some proportion of those who are at risk for it, and among that proportion whose risk is reduced they also reduce the risk of a heart attack in a few, and of death in even fewer.
So, to sum up, "works" is a loaded term. For the case we are discussing, there is what I call a "dwindle" effect, where the main outcome, cholesterol lowering, is likely to show a somewhat robust result. On the other hand, this (surrogate) outcome itself is not all that interesting when divorced from what we really care about -- symptoms, heart attacks and death. And I haven't even gone into the side of the equation where the patient gets to decide what "work" means for him/herself. The layers of the possible "works" are a cabbage that we all need to peel when discussing treatment plans with our clinicians and when reading news about new technologies.
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