I was delighted to read, last week, a lengthy article in the NY Times posing the question that has bothered me for years about the much lauded ‘gold standard randomised, double blind placebo controlled trial’. When every individual is so different physiologically, genetically, mentally and psychologically, each from the other, how can an ‘averaged out’ trial of 20, 200, 2,000 or 20,000 individuals have any validity for any one of them?
The article, by Clifton Leaf, focuses initially on a recent ‘gold standard’ trial on the brain cancer drug Avastin, a trial which showed that some patients did better on the drug, while others didn’t. But the trial gave no indication of who would do better and who would not, or why. And this is after 16 years of human trials, involving tens of thousands of patients, of a drug with $6 billion annual global sales.
‘Which brings us’ Clifton Leaf continues, ‘to perhaps a more fundamental question, one that few people really want to ask: do clinical trials even work? Or are the diseases of individuals so particular that testing experimental medicines in broad groups is doomed to create more frustration than knowledge?
Researchers are coming to understand just how individualized human physiology and human pathology really are. On a genetic level, the tumors in one person with pancreatic cancer almost surely won’t be identical to those of any other. Even in a more widespread condition like high cholesterol, the variability between individuals can be great, meaning that any two patients may have starkly different reactions to a drug.
That’s one reason that, despite the rigorous monitoring of clinical trials, 16 novel medicines were withdrawn from the market from 2000 through 2010, a figure equal to 6 percent of the total approved during the period. The pharmacogenomics of each of us — the way our genes influence our response to drugs — is unique.
It is a fascinating article – I do recommend that you read it.