Medical Progress Today
  Volume 2, Number 9
  March 4, 2005


In the Spotlight

Can Free Market Principles Work With Pharmaceutical Price Controls?

Benjamin Zycher, Ph.D., Center for Medical Progress, 3-3-05

As the costs of drug development are enormous, the prices for many pharmaceuticals are high. And so spending on drugs is substantial. Accordingly, everyone would like cheaper medicines; and because politics is the art of wealth redistribution, the issue of pharmaceutical pricing has reemerged front and center with the new Congress now in session.

Continue reading . . .


Featured News:
A Death Prompts Withdrawal of Promising MS Drug --- Biogen Idec, Elan Recall Tysabri After Users Contract Rare Disorder; Encouraging Words From FDA
Wall Street Journal, 3-1-05
Featured Commentary:
The costs of health care
Doug Bandow, Washington Times, 3-2-05
Featured Research:
Adjuvant Chemotherapy in Older and Younger Women With Lymph Node–Positive Breast Cancer
Hyman B. Muss, M.D., The Journal of the American Medical Association, 3-2-05

News

A Death Prompts Withdrawal of Promising MS Drug --- Biogen Idec, Elan Recall Tysabri After Users Contract Rare Disorder; Encouraging Words From FDA
Wall Street Journal, 3-1-05

Biogen Inc. and Elan Corp. have pulled their highly promising new multiple sclerosis drug, Tysabri, off of the market and suspended clinical trials with the drug following the death of a patient taking it along with an older MS drug, Avonex. Another patient has tested positive for the same rare neurological disorder.

Tysabri was recently granted accelerated FDA approval after initial clinical trial data showed it was “about twice as good as existing drugs in reducing flare-ups of symptoms in MS patients, such as tingling, double vision, and muscle weakness.”

The FDA continues to very supportive of the Tysabri, and most observers believe that it will eventually be returned to market. However, what is alarming about this case is the flurry of criticism that has emerged of the FDA’s accelerated approval program, which is meant to speed patient access to new, promising treatments for life-threatening illnesses. Critics have immediately painted this as another instance of the FDA putting drug companies before patient safety. But the reality is that accelerated approval is a vital tool for getting new drugs to patients with cancer, AIDS, or Alzheimer’s - months or years faster than might be the case under the normal FDA approval process. Comparisons of the Tysabri withdrawal to Vioxx are just inappropriate.

Somehow, we have to recall the reality that disease is our common enemy - not corporations. Other treatments approved through FDA accelerated approval - like antiretroviral treatments for AIDS, or Gleevec for leukemia - have been met with universal praise and applause. But, as the adage goes, how soon we forget.

The reality is that drugs (new or old) - like surgery, or radiation, or chemotherapy - can have tragic unintended consequences. Pills are no different, and no more inherently morally suspicious, than these other instruments of medical progress. Progress depends on accepting some adverse events. Without accepting that trade-off, we wouldn’t have open heart surgery, bone-marrow transplants, or Gleevec. Striving for perfect medical safety would bring progress to a complete grinding halt.

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Are Too Many Unproven Drugs Receiving FDA Early Approval? Process Comes Under Scrutiny
Wall Street Journal, 3-1-05

A bit more background on accelerated approval at the FDA.

Accelerated approval was originally launched by the FDA in the early 1990s in response to criticism from AIDS activists that patients were dying waiting for new treatments to negotiate the lengthy clinical trials needed for FDA approval. Traditional clinical trials depended on validating “endpoints” for proving efficacy - like a survival benefit, i.e. did the patient live longer - that might take years to validate.

Instead, the FDA created an accelerated process whereby promising new treatments for life-threatening diseases could be approved using “surrogate” endpoints - for instance, the amount of circulating AIDS virus in a patient’s blood stream - that might translate into clinical improvements. In return for accelerated access to the market, companies would have to agree to conduct additional clinical studies validating the treatment or risk drug withdrawal.

Does accelerated approval risk missing rare but serious adverse events with new treatments?

The problem is that rare adverse effects are just that - rare. There is no guarantee that they would be identified in the normal approval process, and no reason to suppose that even this adverse effect should hold up a drug as promising as Tysabri. Slowing down acclerated approval in the hope of identifying more potential side effects - including drug-drug interactions, which seems to be the problem in this case - will only keep new treatments away from patients who desperately need them, without necessarily improving drug safety.

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Where Drug's Setback Leaves Patients --- Withdrawal of Tysabri Reshapes Options for Those With Multiple Sclerosis, Crohn's, Severe Arthritis
Wall Street Journal, 3-1-05

Why is Tysabri important?

Autoimmune diseases like multiple sclerosis - including Crohn’s disease, rheumatoid arthritis, and lupus - are amongst the least understood diseases. Doctors can do little more than suppress symptoms or delay the inevitable. Worse yet, even those few treatments that work to some extent (like steroids or immunosuppressants) have devastating side effects of their own.

The withdrawal of Tysabri has “dimmed the hopes of patients with three different debilitating [autoimmune] disorders.” Tysabri had a different mechanism of action than other drugs used to treat MS: binding to immune cells and preventing them from crossing the blood-brain barrier to attack nerve cells. “The different mechanism of action raised hopes that Tysabri could prove a savior for patients who aren’t doing well on the other drugs and also might be used to boost the effectiveness of other treatments.”

“For Crohns’ disease, Tysabri appeared to provide significant relief to half of the patients, and disease remission was long term in half of those…Those are excellent odds for Crohn’s, which is so severe 80% of patients need to have surgery to remove the affected part of the bowel.” All of the extant treatments for Crohn’s “have potentially serious side effects”, including liver toxicity and increased risk of tuberculosis or lymphoma.

This is the hidden side of how the quest for drug “safety” affects patients with diseases for which there are no safe options. Shouldn’t these patients be able to decide for themselves if a potential benefit from a new treatment is worth the risk?

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FDA Drug Approval Times Likely to Grow
Associated Press Newswires, 2-28-05

“The withdrawal of a multiple sclerosis treatment [Tysabri] is likely to lead to even longer product approval times for pharmaceutical companies as pressure mounts on the Food and Drug Administration to improve drug safety, experts say.”

Said one investment analyst: “I think we are in for a dramatic slowdown in the approval process as the FDA wants to see more extensive trials and data.”

The slowdown won’t come as the result of an official mandate - that would be too obvious. Drug reviewers will just keep pushing for more and more safety data and/or additional clinical trials. “If you are a reviewer on the fence wondering whether you should ask for more data, this environment will push you to ask for that data…I think there will be more risk averse decision making.”

Already, the “average time to win FDA approval for a new drug already has risen to about 17 months from 12.6 months in 1999, according to data from the Pharmaceutical Research and Manufacturers of America.” Will this increase in time lead to an increase in safety for patients?

Reason dictates that at a certain point the FDA reaches the margin of diminishing returns, and that additional research has little, if any, real benefits for safety and ever increasing costs to patients - who wait longer for new treatments.

But an extra five or six months of research has real benefits for bureaucrats who may eventually be called to testify before Congress - and that’s what the FDA is worried about right now.

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10 Voters on Panel Backing Pain Pills Had Industry Ties
The New York Times, 2-25-05

There are always things about which people are going to disagree - and the right balance between safety and risk at the FDA is one of those things. Impugning the motives, knowledge and professionalism of one half of those people serves no good purpose.

Preventing conflicts of interest is one thing; impugning the integrity of anyone who has ever had a relationship with industry is something else altogether. The Times points out that “ten of the 32 government drug advisors who last week endorsed continued marketing of the huge-selling pain pills Celebrex, Bextra and Vioxx have consulted in recent years for the drugs’ makers, according to disclosures in medical journals and other public records.”

The Times goes on to note that “if the 10 advisers had not cast their votes, the committee would have voted 12 to 8 that Bextra should be withdrawn and 14 to 8 that Vioxx should not return to the market. The 10 advisers with company ties voted 9 to 1 to keep Bextra on the market and 9 to 1 for Vioxx’s return. The votes of the 10 did not substantially influence the committee’s decision on Celebrex because only one committee member voted that Celebrex should be withdrawn.”

All of the advisors reached by the Times said that their past relationships with drug companies didn’t influence their votes.

Does having a former business relationship impugn the scientific conclusions of the board or the quality of the evidence presented? Isn’t it equally possible that the scientists who had done the most research on these drugs (or the most work on industry projects) might have the best knowledge of their risks and/or benefits? Should we enforce a rule that no one who has worked with industry - or is ever likely to work for industry - should serve an FDA advisory board?

That would preclude either industry or the FDA having access to the best talent available with enormous negative consequences to both groups.

It would also disqualify surgeons from serving on panels investigating the efficacy of surgical procedures, teachers from examining the efficacy of educational programs, and lawyers drawing up ethical standards for lawyers.

One panel member, a neurologist at the University of Pennsylvania, who has “received research support from Pfizer” summed up the point nicely: “I think F.D.A. would have a hard time finding people who are good at what they do who never spoke to a pharmaceutical company.”

This is not to say that conflicts of interest aren’t possible - or that the Times doesn’t have a responsibility to keep the FDA honest. To the contrary. Go find the best scientists who didn’t serve on the panel and ask them to comment on the boards scientific decision. Speak to patients who’ve used the drugs. Review the history of FDA’s rulings on the medicines. All this seems like good reporting, and very much fair game.

But suggesting that the FDA’s advisory system can’t work adequately unless FDA advisors are isolated from industry would bring drug development to a crawl and hurt the very people that everyone is trying to help - the patients.

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Poll: Most Want U.S. Price Limits on Drugs
Associated Press Newswires, 2-24-05

According to a poll taken by the Kaiser Family Foundation, “78 percent of adults say prescription drugs make a ‘big difference’ in people’s lives, and 91 percent believe drug companies contribute significantly to society by researching and developing new drugs.”

Nonetheless, 70 percent of respondents think drug companies are more concerned with profits than developing new drugs, and 65 percent want price controls or legislation that would allow large scale importation from Canada (73 percent).

How can we reconcile these seemingly contradictory findings?

First we have to remember that, unlike hospital care or visits to doctor’s offices, prescription drug coverage is the single largest out-of-pocket health care cost for most Americans. The relative prices of those other forms of care dwarf that of prescription drugs, but since consumers don’t pay their own hospital bills, they don’t become irritated with hospitals in the abstract.

Second, thanks to our third-party payer system, patients have come to think of health care as a right, something that ought to be free. Most health care costs are hidden from consumers. The pharmaceutical companies may seem unbearably greedy and heartless compared to a family doctor who may have just socked your insurer $500 or more for a 15 minute check up.

Dollar for dollar, pharmaceuticals are among the most cost-effective forms of medical treatment available. Their share of total U.S. health care spending has remained relatively stable (11.8% in 1960; 10.8% in 2000).

As long as there is a gap between how we insure pharmaceuticals vs. other forms of health care, pharmaceutical companies will bear undue stigma, although, in reality, they deserve much more praise than blame.

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Glaxo Drug Quickly Suppresses HIV in a Human Clinical Trial
Wall Street Journal, 2-5-05

Researchers note that a GlaxoSmithKline drug given “fast track” status by the FDA has shown promising results in an early clinical trial and “suppressed blood levels of the AIDS virus in 31 patients by about 98% after just 10 days of treatment.” The drug, called by the charming name 873140, “blocks entry of the AIDS virus into human cells” via what is known as a CCR5 receptor, one of the cellular “doorways” the virus uses to enter human cells.

Researchers were excited by the early findings, and pointed out that “the agility of the AIDS virus in developing resistance to existing types of AIDS drugs makes new classes of drugs [like this one] ‘absolutely critical.”

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Commentary

The costs of health care
Doug Bandow, Washington Times, 3-2-05

Bandow points out that federal and state governments are desperate to reign in spiraling health care costs. “As America’s population ages, outlays will only increase. The Office of the Centers for Medicare and Medicaid Services (CMS) recently projected that health care spending could double by 2013, accounting for 18.4 percent of GDP.” However, drug spending has attracted more than its fair share of attention given its overall share of health care costs relative to, say, spending on hospitalizations.

“[T]he CMS reports that of the $1.6 trillion spent in 2003 on health care services and supplies, only $179 billion, or about 11 percent, went for drugs. And that figure includes payments for generic products and to pharmacies.”

Bandow also notes that economists widely praise the cost-effectiveness of prescription drug spending versus other forms of health care. “The added costs associated with breakthrough drugs represent a major structural shift from the provision of traditional medical services to the consumption of medical products, a systemic rotation from labor to capital.” Costs aren’t unimportant - but when it comes to pharmaceutical spending and patient health we really are getting more bang for our buck.

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Drug Twilight Zone
Wall Street Journal, 3-2-05

The Journal believes that the Tysabri withdrawal has little to do with science and a lot to do with politics—Biogen and Elan didn’t want “to have their names dragged before Capitol Hill cameras by Ted Kennedy or Chuck Grassley.” So as two companies minimize their risk profile for a few months, MS patients have to go back to their old, less effective treatments. Perhaps Kennedy and Grassley should hold a hearing on that problem.

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Conflict on drug reviews
The Star-Ledger, 2-28-05

“The Center for Science in the Public Interest analyzed the allegiances of scientists on the FDA panel at the request of the New York Times. Of 32 panel members, 10 had been consultants or paid speakers for Merck, and two other big COX-2 firms. The FDA said that it doesn’t matter, that there were no conflicts. That point of view is part of the problem. Anyone with financial ties to the products under review should not have been on the panel.”

But past ties to industry do not translate into present ties to the products under review. Furthermore, it is eminently arguable that scientists who study these drugs and consult with industry on their development know them better than anyone else.

In the final analysis, we have to get back to the objective science.

Was this a class of drugs (painkillers) worth creating given the limitations of existing treatments? Yes. Do they serve a valuable purpose for a real group of patients. Yes.

Were these drugs over prescribed? Most likely. Therein lies the real problem, but it’s a much tougher nut to crack than simply decrying industry influence at the FDA.

The Star-Ledger suggests that the unholy influence of industry on the FDA can only be broken if “people who have accepted money from pharmaceutical companies are not on panels reviewing those companies or their competitors.” Is this true?

We respectfully disagree. There is no reason to expect that the best scientists in academia should recuse themselves from financial gain from their research, and nothing to gain by forbidding them to do so. Medical progress depends on close cooperation between industry, government, and academic scientists and bottle-necking cooperation between any two of those groups will have perverse consequences for the entire enterprise.

If we want to improve safety at the FDA, we should concentrate on improving the science and technology it uses to evaluate new drugs and monitor drug safety because only that knowledge will really enable us to save lives.

Otherwise we will lose sight of our goal in an impossible quest to weed out that most nebulous of human factors: “influence.”

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BACK TO SANITY ON COX-2 DRUGS ; PATIENTS, DOCTORS CAN WEIGH RISK, REWARDS
Rocky Mountain News, 2-28-05

The Rocky Mountain News lauds the FDA advisory panels’ decision to keep Cox-2 drugs on the market, a gain “for people who need chronic pain management versus pain for the trial lawyers who hoped to litigate the pharmaceutical industry into oblivion. It’s about time the nation’s months- long panic over Cox-2s came to an end. While the panel’s decision helps restore sanity to the market for future drug development, far more important is its recognition that those drugs have huge benefits and that their risks should be weighed by doctors and patients.”

We concur. Some critics, unable to dispute the science behind this decision, have chosen instead to attack the FDA and its advisory boards as hopelessly corrupt - which also happens to benefit the trial lawyers who need to cast the FDA and its advisors as industry shills if they are to have any hope of creating a multi-billion dollar payday from the Vioxx debacle.

This tactic is misleading and does a disservice to the patients who depend on these drugs for relief from unremitting pain.

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Reducing Barriers to the Development of High Quality, Low Cost Medicines: A proposal for Reforming the Drug Approval Process
International Policy Network, 2-28-05

IPN argues that prescription drugs are expensive “because of a lack of competition in the drugs approval process. Lack of competition…has led to exceedingly high drug development costs combined with artificially low drug prices, obtained through price control legislation and legislation that eases the entry of generic products into the market, has caused lower levels of pharmaceutical research and development, innovation, and economic growth.”

In its place, IPN calls for “private drug certification bodies (DCBs)” which would “compete for assessment of the safety and efficiency of new dugs, and also grant final drug approval. The importance of regulation in maintaining clients and attracting new ones, the existence of a free press engaging in investigative journalism, and expected penalties through the legal system for corrupt and dangerous decisions..should be sufficient to establish a well-functioning market in drug approval.”

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Research

Adjuvant Chemotherapy in Older and Younger Women With Lymph Node–Positive Breast Cancer
Hyman B. Muss, M.D., The Journal of the American Medical Association, 3-2-05

There has been some concern that although “adjuvant chemotherapy improves survival for patients with local-regional breast cancer, healthy older patients at high risk of recurrence are frequently not offered adjuvant chemotherapy, and the benefit of adjuvant chemotherapy in older patients is uncertain.”

This study “compare[s] the benefits and toxic effects of adjuvant chemotherapy among breast cancer patients in age groups of 50 years or younger, 51 to 64 years, and 65 years or older.” The researchers find that “smaller tumor size, fewer positive lymph nodes, more chemotherapy, and tamoxifen use were all significantly...related to longer disease-free and overall survival. There was no association between age and disease-free survival.”

However, “survival was significantly worse for patients aged 65 or older because of death from causes other than breast cancer. Thirty-three deaths…were attributed to treatment, and older women had higher treatment-related mortality. Older women and younger women derived similar reductions in breast cancer mortality and recurrence from regimens containing more chemotherapy.”

The researchers concluded that “age alone should not be a contraindication to the use of optimal chemotherapy regimens in older women who are in good general health.”

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Medical Progress Today is published by the Center for Medical Progress at the Manhattan Institute for Policy Research.

For more information about Medical Progress Today, please contact the managing editor, Paul Howard, at phoward@manhattan-institute.org, or via telephone at 212.599.7000, x319.

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SPOTLIGHT

Can Free Market Principles Work With Pharmaceutical Price Controls?

NEWS

A Death Prompts Withdrawal of Promising MS Drug --- Biogen Idec, Elan Recall Tysabri After Users Contract Rare Disorder; Encouraging Words From FDA
Are Too Many Unproven Drugs Receiving FDA Early Approval? Process Comes Under Scrutiny
Where Drug's Setback Leaves Patients --- Withdrawal of Tysabri Reshapes Options for Those With Multiple Sclerosis, Crohn's, Severe Arthritis
FDA Drug Approval Times Likely to Grow
10 Voters on Panel Backing Pain Pills Had Industry Ties
Poll: Most Want U.S. Price Limits on Drugs
Glaxo Drug Quickly Suppresses HIV in a Human Clinical Trial

COMMENTARY

The costs of health care
Drug Twilight Zone
Conflict on drug reviews
BACK TO SANITY ON COX-2 DRUGS ; PATIENTS, DOCTORS CAN WEIGH RISK, REWARDS
Reducing Barriers to the Development of High Quality, Low Cost Medicines: A proposal for Reforming the Drug Approval Process

RESEARCH

Adjuvant Chemotherapy in Older and Younger Women With Lymph Node–Positive Breast Cancer
Center for Medical Progress 
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52 Vanderbilt Avenue
New York, NY 10017
(212) 599-7000
mpt@manhattan-institute.org