“Is the scientific paper a fraud?” asked Sir Peter B Medawar, Nobel Laureate in the Listener (12 Sep 1963), 377-78.
W e claim that our research, which is based on the short-term randomised controlled trials (RCT), is very scientific and based on evidence. Is this premise right? Do our RCTs, even remotely, have anything to do with reality and science? I do not think so, especially in the realm of so-called killer lifestyle diseases like hypertension, diabetes, cancer and coronary artery disease.
Hypertension has been my research interest for more than four decades; I have had a feeling that we have been predicting the unpredictable future of our patients based on our short and ‘dirty’ experiments called RCTs where the researcher can manipulate one measure in the cohort as s/he wants.
Long-term observational studies, on the other hand, allow one to study what happens to the subjects over a period of time where one cannot manipulate the measures. This apart, humans are not identical, like molecules in a laboratory, to be compared with others.
I had written about this in my book on hypertension, in 1993. In retrospect, three major very long-term observational studies have now proved me right. Multiple risk factor intervention trial (MRFIT) study is a very long-term observational study of a large cohort over a period of 25 long years. It has proved that both, hypertension and diabetes, are, at best, ONLY risk factors. MRFIT clearly showed that there have been NO RISK FACTORS that could lead to heart attacks and stroke.
Even if one were to believe in the risk factor theory and modify those risk factors with outside interventions, the risk will still be the same! MRFIT clearly shows the hollowness of our thinking in this area. What is average for the general population may be an alarming disease for any given person when we treat averages as normal in our RCTs which give a distorted version and label many healthy people as sick needing unnecessary intervention (false positives); but the industry loves that.
“Longitudinal monitoring can look at trends as a function of age in the same person, starting with presumably healthy subjects,” feels Germaine Cornellissen, head of the Halberg Chronobiology Centre at the University of Minnesota. He feels that “Blood pressure and heart rate rise during the day and fall at night. The changes are under control of the brain’s master clock, the suprachiasmatic nucleus, which orchestrates the body’s circadian rhythms. Some diagnosed cases of high blood pressure are accompanied by large swings; a daytime measure of high blood pressure may actually become low blood pressure at night, and there are some indications that this change may be a bigger concern than blood pressure itself.”
I had been opposing the night doses of BP pills for this very reason; lest I should fall into the trap of disregarding primum non nocere (first do no harm)!
Studying BP over a period in the same person would give us great insight into this enigma called hypertension, if it is a disease at all. Labelling hypertension with one or even many readings over a short period might have a specificity and sensitivity of less than 50% making it look like a roulette game—a big gamble.
Of course, people have studied continuous BP monitoring over a period, may be for days at best; but that does not refine the diagnosis significantly. I tried it and stopped doing that when I realised the futility of that approach.
I am reminded of what the German author, Jorg Blech, wrote in his book Disease Inventors
about the early days of labelling hypertensives in those small cute WellMan clinic
vans outside the churches and malls in Germany offering to check their BP for free! This is how it all started. He opposed it then; see how right he was in the light of new knowledge! (Inventing Disease and Pushing Pills: Pharmaceutical Companies and the Medicalization of Normal Life, Routledge, 2006
). The new findings suggest that these vascular variability disorders, called circadian over-swings, might be labelling healthy people as hypertensive when the measures of BP are checked at noon in the doctors’ clinics only. Some patients even have a shift in their timings where they peak at night and are low during the day, out of synch with the rest of their body.
Another large study, of more than 75 years’ longitudinal observation of a large cohort of healthy young men after the Second World War (The Grant and The Gluech studies), by a group of researchers from Harvard (going on to the third generation of researchers today) has thrown up some scientific surprises in this area; alcohol and smoking are the greatest killers. Love, compassion and strong relationships, including social support, came out as the leading causes of happiness and longevity. In short, as Dr George Vaillant put it “happiness and good health is love.”
A study at Tokyo Women’s Medical University tracked BP based on multiple readings (almost monitoring it) over a 48-hour period to separate simple raised pressures from those with vascular arhythmicity, either in the size of the change or in its timing.
This, in itself, has thrown up some surprises; but the next six years’ follow-up showed that only 10% of those with genuine high BP had cardiovascular (CVS) events. Even in those with vascular problems, ONLY 29% had CVS problems. Surely 10% and 29% do not by themselves make BP a risk factor. However, in today’s world, even one raised reading, warrants chemical drugs which looks dangerous, to say the least. Of course, this is only a women’s study and has its shortcomings vis-à-vis men.
RCTs, especially short ones, in small cohorts funded by the industry, have been a menace in the area of coronary interventions. Whereas there are no large-scale studies of either bypass surgery or angioplasty having any special benefit except pain relief, there are many small RCTs showing multiple benefits from angioplasty and coronary artery bypass grafting (CABG).
None of those, so-called, studies has observed the patient after intervention on a long-term basis, like the observational studies quoted above. Our experience of industry-funded studies, which are published selectively and suppresses negative studies, makes the scenario in this area doubtful. In practice, they have become a menace for poor patients. See this pathetic note from a patient’ son which I received recently:
“Sir, yesterday evening my mother got heart attack, so we took her to… heart centre, and they (have) done angioplasty and placed 3 stents. They are saying that (the) cost will be around Rs6 lakh. I cannot afford this much sir. I spoke with (the) management. They (are) saying that if our chairman agrees, they will make it in lower cost. So I request you, if possible, please speak with Dr…. and make the bill subsidised, sir.”
Is it a stent or an unscientific stunt?
“One of the most successful physicians I have ever known has assured me that he used more bread pills, drops of coloured water, and powders of hickory ashes, than of all other medicines put together. It was certainly a pious fraud.”— Thomas Jefferson