The false belief that all drugs will work on everybody

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http://www.commondreams.org/cgi-bin/print.cgi?file=/headlines03/1208-01.htmDemolished: The Myth That Allows Drugs Giants to Sell Moreby Steve ConnorFor years, the drugs industry has grown fat on a myth - the false beliefthat all drugs will work on just about everybody.That has essentially been the rationale for a culture that has encourageddoctors to prescribe first and ask questions later - at a cost to the NHS of£7.2bn a year in medicines.Yet it has been an open secret within the drugs industry that most drugs donot work for most patients, a secret that has now been publicly aired forthe first time by Allen Roses, the head of genetics at GlaxoSmithKline,Britain's biggest drugs company.Also See:Glaxo Chief: Our Drugs Do Not Work on Most PatientsDr Roses, an academic with a distinguished record in medical genetics, isused to speaking his mind, especially on the benefits of a revolutionary newapproach to drug development called pharmacogenomics.That is the science of applying the results of the human genome project todrug development. In essence, it means testing the DNA of patients in orderto identify those for whom a particular drug will work - the "responders".That would enable doctors to eliminate the "non responders" who, as aresult, will at least not be given a drug that at best could be useless andat worst dangerous in terms of harmful side-effects.In the past, drug companies have developed drugs aimed at the widestpossible population. That was the most profitable strategy but one thatignored a basic fact in biology - people are different.To emphasize the point, Dr Roses likes to quote Sir William Osler, aCanadian physician who in 1892 remarked: "If it were not for the greatvariability among individuals, medicine might as well be a science and notan art."Bringing a new drug to market is an expensive business costing tens ofmillions of pounds. It takes place in a culture of maximum possible salesfor maximum possible profit - a culture that does not like to broadcast thefact that most drugs don't work for most people.Drug testing in patients involves three phases of increasingly complexclinical trials that must be successfully completed before the drug isapproved by regulatory authorities such as the mighty US Food and DrugAdministration.But even when a drug has been approved in terms of safety and "efficacy" -whether it does what the label says it should do - few people realize justhow poorly they perform in real life.Dr Roses cited a study published three years ago by Brian Spear, a seniorscientist at Abbott Laboratories, a medical diagnostics company in Chicago,on the efficacy rates of a range of different drugs.It found that drugs vary enormously in terms of how well they work, withefficacy rates varying from as low as 25 per cent for cancer drugs to 80 percent for painkillers.For many drugs, however, the efficacy rates hover around 50 per cent orlower, meaning that, for most people, these drugs just don't work. As DrRoses puts it: "The vast majority of drugs - more than 90 per cent - onlywork in 30 or 50 per cent of the people."Dr Roses is one of the pioneers in a field of genetics that promises to helpto identify those people who could benefit from a drug. It is called singlenucleotide polymorphisms (SNPs) and it is a way of distinguishing thesmallest possible genetic differences between individuals.The use of SNPs has already led to the discovery, for instance, of a test todetect the 5 per cent of the population who inherit a predisposition to apotentially fatal side effect of an anti-HIV drug called abacavir.Now it is possible to test HIV patients before the drug is given to them inorder to weed out those patients who will suffer a severe adverse reaction -a violent rash on the body.Scientists believe that SNPs can be used to test people not just for theirvulnerability to a drug's side-effects, but also to whether it will work ornot.John Bell, the regius professor medicine at Oxford University, said that forpharmacogenomics to catch on, doctors will have to learn new ways of dealingwith patients."One of the biggest obstacles is culture. We've all been taught to take thedose for a drug straight out of the British National Formulae and then ifthat doesn't work to add another drug to the prescription, and so on,"Professor Bell said."So we can end up with lots of patients on four or more drugs where only onewould do. This is a big cultural issue to overcome," he said.Apart from the ethics of prescribing useless drugs to people who could bepoisoned by them, there is also the question of costs to the NHS, which hasseen a record 50 per cent increase in its drugs bill over the past threeyears.As Bill Clarke, the executive vice president of research at Amersham, aBritish diagnostics company, said: "It's just not right to spend that amountof money on drugs that don't work." For the sake of a relatively cheapgenetics test that can be carried out on the wider population of patients,it would be possible to target drugs more effectively and more safely, DrClarke said.It could also lead to a revolution in the way drugs are tested, he said. If"responders" to a new drug can be identified easily, it will be possible tosimplify the expensive phase 3 clinical trials which can involve thousand ofpeople being followed over many years.Dr Roses agreed: "You can pick out people who respond a lot to the drug, canyou pick out people who do not respond at all to the drug and can you pickout people who are sort of in the middle."By eliminating the people that we predict will be non-responders we'll beable to do smaller, faster and cheaper drug trials."That could be the incentive that will lead to a change in the"one-drug-fits-all" culture of the drug industry, he said."I can't speak for other companies but I can tell you absolutely for surethat there is a change in the culture of GSK," Dr Roses said. And the adventof pharmacogenomics will not necessarily mean a fall in sales."If you can determine who is going to have a response [to a drug] and who isnot going to have a response, you can take your next molecule and aim itspecifically at the people who haven't had a response with the first one sothat you can create a set of drugs that cover the population, and then youare back to selling to everybody," he said.Trial approachPHASE I: These first studies evaluate how a new drug or therapy should begiven (by mouth, injection into the blood or injection into the muscle), howoften, and what dose is safe. A phase I trial usually enrolls a small numberof patients, sometimes as few as a dozen.PHASE II: A phase II trial usually focuses on one type of illness,continuing to test the safety of treatment and beginning to evaluate howwell it works. This is the essential intermediate step that will determinewhether the drug will go into bigger and more costly phase III trials.PHASE III: These studies test a new drug, a new combination of drugs or anew therapy in comparison to the current standard treatment. A participantwill usually be assigned to the standard group or the new group at random(called randomization). Often it involves "double blind" trials, whereneither the patient nor doctor knows who is being given the new drug. PhaseIII trials often enroll large numbers of people and may be conducted at manydoctors' offices, clinics and cancer centers nationwide.