Re: In short drug tests, fatal flaws

[Guest guest]

Very good article, a. A must read for everyone here.

[ ] In short drug tests, fatal flaws

> In short drug tests, fatal flaws

>

> A narrow focus on effectiveness is a prescription for harm

>

> By J. , 7/14/2002

>

> It is a major medical debacle when hormone replacement therapy - a drug

> treatment that doctors recommended to millions of women - is discovered to

> be harmful despite 60 years of widespread use. Yet because of weaknesses in

> the entire system that tests and promotes drugs for long-term use, this

> major surprise surely will not to be the last.

>

> The Women's Health Initiative trial provides an object lesson about how

> easily some inadequately-tested drug treatments can cause harm. These

> findings speak with unusual authority because they come from one of the

> largest, longest, and best-designed clinical trials reported in many years.

>

> So what was the magnitude of the hormone replacement debacle? Estrogen and

> progestin significantly harmed about 1 percent of the women tested over the

> 5.2 years they took the hormones, but caused no additional deaths. The

> harmful events included breast cancer, stroke, heart attack, or blood clots

> in the lungs. In addition, about a third of treated women had gynecological

> symptoms requiring a doctor's care.

>

> How could this happen with one of the most extensively researched,

> high-visibility treatments in all of medicine? It occurred, and will happen

> again, for three reasons. First, our society settles for short-term studies

> about drugs taken for long-term effects. Second, the health professionals

> tend to see drugs with tunnel vision, focusing narrowly on a particular

> benefit while forgetting that drugs have many effects. Finally, many popular

> long-term treatments provide very small benefits to people with an already

> low risk of death or serious injury. In such circumstances, only a small,

> unintended effect tips the balance from good to harm.

>

> To get new drugs more quickly, drug testing worldwide is often extensive,

> but lasts only for short periods. Antidepressants are usually tested for six

> weeks, new blood pressure drugs for a matter of months, and drugs for

> adult-onset diabetes from six months to a year. To limit development costs,

> an individual trial for Food and Drug Administration approval seldom has

> more than a few hundred participants.

>

> The harm of hormone replacement therapy was detected only because taxpayers

> paid for a much larger, longer trial with 16,608 participants who were going

> to be observed for 81/2 years.

>

> This is hardly the first time that long-term trials conducted at government

> expense have produced findings of harm. A heart drug called Tambocor,

> effective in the short term in suppressing mild irregular heartbeats, was

> discovered in a longer government trial to cause people to drop dead with

> cardiac arrest. Cardura, a blood pressure drug, was found inferior to other

> drugs in another large, long-term study conducted by the National Institutes

> of Health. In other long studies, two cholesterol-lowering drugs were found

> to be harmful overall, even though they lowered cholesterol.

>

> However, no system is in place to ensure that drugs intended for long-term

> treatment ever receive long-term testing. The legal structure of our

> drug-approval laws has been built around simpler drugs such as painkillers

> and antibiotics - which are taken for short periods of time with effects

> that are more immediately apparent.

>

> As a result, we know little about the long-term effects of many important

> drugs. For example, millions of schoolchildren take Ritalin and other

> powerful stimulants for years without long-term trials to establish safety,

> and despite evidence they cause brain damage in some children. The long-term

> benefits of some best-selling drugs to lower cholesterol or blood pressure

> are similarly unknown. Although many popular drugs caused cancer in animals,

> few have been tested for the five years or longer needed to document excess

> cancer risks in humans.

>

> Until the hormone trial results were published, the scientific case for

> estrogen replacement therapy seemed persuasive, so long as focus was limited

> to just part of the evidence. Estrogen does preserve bone density, and the

> Women's Health Initiative confirmed its ability to reduce bone fractures.

> Estrogen also lowered ''bad'' (or low-density) cholesterol, so it seemed

> reasonable to presume it would prevent heart attacks.

>

> But drugs have many effects, and these were only two. Estrogen is also a

> powerful growth promoter, and it is also reasonable to assume it might

> accelerate the growth of some cancers. It also increases blood clotting, and

> therefore might cause heart attacks and dangerous blood clots in the lungs

> and legs. These effects were well documented in scientific literature, along

> with the benefits, but many doctors ignored them. Only a large, long-term

> clinical trial such as the Women's Health Initiative was capable of

> providing a conclusive, balanced perspective on all the risks and benefits.

>

> Examples abound of this medical tunnel vision. Many clinicians have embraced

> two heavily marketed drugs for adult-onset diabetes called Actos and

> Avandia. These drugs had a small effect in lowering blood sugar (the benefit

> the doctors saw) but also increased stress on the heart and induced weight

> gain (the drawbacks that get little attention).

>

> Without a long-term trial of about 10 years, no one knows whether the net

> effects on health are harmful or beneficial. Doctors and patients alike

> embraced an arthritis drug called Vioxx, impressed by evidence that people

> had fewer stomach ulcers of microscopic size compared to ibuprofen and

> naproxen. But few noted that Vioxx lacked the cardioprotective effects of

> naproxen until hard evidence emerged in another large clinical trial. For

> many people, a greater risk of a heart attack or stroke with Vioxx might

> outweigh any benefits from fewer injuries to the digestive tract. In each of

> these cases, the lesson is that drugs have many effects, not just the

> benefits used for marketing and promotion.

>

> The hormone replacement debacle also illustrates why relatively small

> adverse effects can render a drug treatment harmful overall. The reason is

> that the participants - two-thirds from 60 to 75 years old - were remarkably

> healthy regardless of whether they took a placebo or the hormone replacement

> therapy. Over five years only 52 of 8,102 older women taking the placebo

> died of breast cancer, colorectal cancer, heart attack, or stroke - less

> than 1 percent. Among people so healthy it is extremely difficult for a drug

> to have a beneficial effect because there is so little room for improvement.

>

> That fact also doomed the most important benefit of hormone replacement

> therapy - prevention of hip fractures. Despite an avalanche of medical

> advertising about the dangers of osteoporosis, hip fractures were rare. Just

> 62 hip fractures occurred in the placebo group, compared with 44 among those

> on hormone replacement. Helping just 18 women avoid a hip fracture among

> more than 8,000 treated was a benefit so tiny it was outstripped by very

> modest increases in strokes, breast cancer, and heart disease.

>

> How many drugs are so completely free of adverse effects that fewer than 1

> person per 1,000 per year is injured? Yet an adverse effect of that rarity

> nullifies the protection against hip fractures provided by hormone

> replacement therapy. One has to wonder whether many drugs targeted at a

> population with such an excellent health status are destined to fail in a

> large clinical trial capable of detecting risks and benefits that are this

> small. Yet the pharmaceutical industry loves to market drugs to the

> healthiest people because there are so many of them, and the largest market

> yields the most money.

>

> It is also noteworthy that the important but unwelcome findings of the

> Women's Health Initiative came in an NIH study conducted by medical

> investigators without a financial stake in the outcome. What if this study

> had been sponsored by a pharmaceutical company whose stock would plummet,

> and if the investigators were bound by secrecy agreements not to reveal the

> findings? Furthermore, the companies have no legal obligation to make public

> such findings.

>

> Every large complex clinical study raises questions capable of triggering a

> technical debate over the validity of its findings. Scientists can find just

> as many technicalities to debate as a skilled lawyer with a guilty client.

> It does not even take the assumption that companies would deliberately fudge

> the numbers - as so many large corporations now stand accused of doing. A

> fat consulting fee to a specialist with sterling credentials who is willing

> to advance one side of a technically-arguable issue is all it would take to

> mire important findings in an endless technical debate. For this reason,

> drug companies with a financial stake in the outcome should not be allowed

> to control these large, long-term studies.

>

> We need new laws, a national scientific program, and money to assure that

> every important drug intended for long-term use receives the same long-term

> testing as was provided for hormone replacement therapy. The funds should

> come from a new tax on the pharmaceutical companies that profit from the

> sale of such drugs.

>

> It now remains to be seen whether Congress and the Bush administration will

> respond to this clear public need - or to the millions of dollars spent on

> pharmaceutical lobbying. But the fact remains that drugs intended for

> long-term use require long-term testing. And under our present system they

> don't get it.

[Guest guest]

Yes it is . I was shocked to read the antidepressants are just tested

for 6 weeks!!!!

That¹s awful. I though fast tracking approvals only were for life

threatening diseases.

Makes me really wonder.

a

> Very good article, a. A must read for everyone here.

>

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