Category Archives: Patents

Generics and Evidence based medicine–Big Pharma’s influence

It’s about the money, not the patient!

It’s not surprising to hear that drug companies try to block the release of competing lower cost products. Our patent system has become an instrument of monopolies and needs revision.

Add that to pharmaceutical companies’ campaigns to undermine evidence based recommendations of less expensive medications and you have a system based on maximizing cost not benefit.

“A confluence of factors blunted Allhat’s impact. One was the simple difficulty of persuading doctors to change their habits. Another was scientific disagreement, as many academic medical experts criticized the trial’s design and the government’s interpretation of the results.”

“Moreover, pharmaceutical companies responded by heavily marketing their own expensive hypertension drugs and, in some cases, paying speakers to publicly interpret the Allhat results in ways that made their products look better.”

In the U.S. value and cost/effectiveness are deemphasized as considerations in treatment decisions. Providers are influenced in many ways in their choices for patients. One would hope that patient outcome is the primary concern but it appears that personal gain, drug company emollients, and over the top pharmaceutical company advertising are major factors as well.

We can’t afford our health care and 50 million people have no health coverage; medical expenses are among the leading causes of bankruptcy; and our health outcomes are mediocre when compared with other industrialized countries.

This is not a great advertisement for the so called “free market” system.

Powered by Zoundry Raven

Free Markets in Healthcare, another medical oxymoron

There are many indications that there is no real health care “market.” That is health care companies, practitioners and suppliers competing for customers in a open system with transparency and equal open access to information about costs and quality. This article from the Boston Globe lifts the veil on pricing variations in Boston

“One reason patients don’t shop for care is that, as a practical matter, they can’t. The pay rates of different caregivers have long been treated as confidential data, veiled by nondisclosure agreements between insurers and hospitals. As a result, there has been no public notice or debate as an insurance system that a decade ago paid hospitals and doctors similar amounts for the same work has grown into one that disproportionately rewards a few.”

And if the consumer shopped for his care:

“I think a consumer that relies on the cross-section of information that’s out there and available to them, it’s akin to being a cork floating in the ocean,” said Dr. David F. Torchiana, head of the Massachusetts General Physicians Organization. “You’ll be driven in random directions by the randomness of the information that you will obtain.”

The confidentiality and closed nature of the system breeds unequal payment for care. We’re talking thousands of dollars difference for the same procedure done by similarly qualified practitioners with similar outcomes.

“If the white slip of paper directs him to do the procedure in Framingham, the insurance company will pay the hospital about $17,000, not counting the physician’s fee. If Alderman is sent to Brigham and Women’s Hospital in Boston, that hospital will get about $24,500 – 44 percent more – even though the patient’s care will be the same in both places.”

“The Blue Cross data show that about 10 hospitals – four Boston teaching hospitals and six community hospitals – are paid at least 30 percent above the state average, while 12 hospitals make at least 20 percent below average, including Cambridge Hospital, which earns about half as much per procedure as the Brigham and Mass. General.”

The system is set up a bit like a shell game. Information is withheld so as to manipulate the system. Pricing is “confidential,” the amounts paid by our insurers for our care, is not available, and the the efficiency and quality of the various provider never evaluated or revealed. In Massachusetts, by the way there doesn’t appear to be wide variations in quality to justify the price differential.

What’s damning about health care in the U.S. is that corporate and non-profit supplier’s main interest is in maintaining profits for stockholders or to increase their hold on the market, not assuring quality affordable healthcare.

Meanwhile the notions of value and efficiency in health car go begging. We need change!!

Powered by Zoundry Raven

Powered by Zoundry Raven

The rosuvastatin (Crestor) Jupiter study–Watch your wallet

This week we were inundated with reports of a major study with near miraculous results. Just under 18,000 participants in the Jupiter study either received rosuvastatin (Crestor) or placebo. Patients were chosen to participate if they had low LDL cholesterol (under 130 mg/deciliter) and elevated C-reactive protein (above 2 mg/liter). The results, as summarized, in a accompanying editorial :

The trial of nearly 18,000 patients was stopped, with only 1.9 of its proposed 4 years of follow-up concluded, when the data and safety monitoring board noted a significant reduction in the primary end point among participants assigned to receive rosuvastatin (142 primary events, vs. 251 in the placebo group; hazard ratio, 0.56; 95% confidence interval [CI], 0.46 to 0.69). There was a similar reduction in a combination of the more important hard outcomes: myocardial infarction, stroke, or death from cardiovascular causes (83 events in the rosuvastatin group vs. 157 in the placebo group; hazard ratio, 0.53; 95% CI, 0.40 to 0.69).

The study also reported virtually no extra side effects among the study patients. “Total numbers of reported serious adverse events were similar in the rosuvastatin and placebo groups (1352 and 1377, respectively; P=0.60) Nineteen myopathic events were reported (in 10 subjects receiving rosuvastatin and 9 receiving placebo, P=0.82)” There was one case of major muscle lysis problems (rhabdomylysis) in a 90 year old man after the study was completed. Virtually all other toxicity was equivalent between drug and placebo.

Medicynical note: As noted above the finding that there was no difference in side-effects between the drug and placebo is at least a little strange. That the reported side effects occurred much less frequently even than the incidence in the FDA drug insert also is remarkable. It could indicate patient selection or bias from in this drug company sponsored trial. Interestingly 25% of patients were reported not taking the drug at the end of the study. Why? That’s left to the imagination.

From the drug insert:

In clinical studies of 10,275 patients, 3.7% were discontinued due to adverse experiences attributable to rosuvastatin. The most frequent adverse events thought to be related to rosuvastatin were myalgia, constipation, asthenia, abdominal pain, and nausea.”

Uncomplicated myalgia has been reported in rosuvastatin-treated patients (see Creatine kinase (CK) elevations (>10 times upper limit of normal) occurred in 0.2% to 0.4% of patients taking rosuvastatin at doses up to 40 mg in clinical studies. Treatment-related myopathy, defined as muscle aches or muscle weakness in conjunction with increases in CK values >10 times upper limit of normal, was reported in up to 0.1% of patients

The NEJM editorial about the study also noted:

On the other side of the balance, of concern are the significantly higher glycated hemoglobin levels and incidence of diabetes in the rosuvastatin group in JUPITER (3.0%, vs. 2.4% in the placebo group; P=0.01). There are also no data on the long-term safety of lowering LDL cholesterol to the level of 55 mg per deciliter (1.4 mmol per liter), as was attained with rosuvastatin in JUPITER, which is lower than in previously reported trials. Long-term safety is clearly important in considering committing low-risk subjects without clinical disease to 20 years or more of drug treatment.”

An additional concern is cost.

“The proportion of participants with hard cardiac events in JUPITER was reduced from 1.8% (157 of 8901 subjects) in the placebo group to 0.9% (83 of the 8901 subjects) in the rosuvastatin group; thus, 120 participants were treated for 1.9 (Medicynical note: 693 days) years to prevent one event.

At a cost of $3.45/day treating 120 patients for 693 days is a total of almost $300,000 spent to prevent one event. This is far above any reasonable cost/effective intervention. It’s obvious why this information was not included in this drug company sponsored study. It is, however, one of the major concerns we all should have in this time of crisis in health care.

Having patients commit to take a medication for the duration of their lives to prevent serious medical problems is the dream of drug companies. But in order to seriously consider such an intervention, it must be very effective, have low toxicity and be affordable both for the patient and the health care system. Use of rosuvastatin to prevent cardiovascular disease doesn’t fully meet these criteria and as such, the report should be viewed as an interesting approach that merits further study, not wholesale adoption.

In the press I noted comment that other statins that are available as generics may have the same beneficial effect at lower cost. It’s unlikely however, that drug company sponsored studies of these low cost alternatives will ever be done.

A first step to health care for all–reforms that won’t cost a penny

Price competition is fundamental to the capitalist system. In a perfect world, competition leads to the right price for product and results in value to consumers. Such competition however is anathema to health care.

Why?

On one hand we have patent monopolies which allow patent holders to charge whatever they want for a product for a generation.

Second we find it difficult as a society, as health providers and as consumers to place a monetary value on health care, a surrogate for life itself.

Third, the system is full of conflicts of interests. Providers, patients and industry all have agendas. Patients want to live but don’t fully understand the nuances of the decision. Pricing information is hard to find. Industry’s interest is in profits not the best health care decision. Information on health care decisions is complex and guarded. As a result value in medicine is an oxymoron.

I’ve focused on cancer medicines in previous posts in part because pricing is extreme and also because patients with cancer perceive that they face the ultimate dilemma-pay or die. Cancer pharmaceutical pricing is indeed a death tax, a system that redistributes wealth rather than assures quality care at reasonable price.

The question is whether there is, or should be, a quid pro quo for a government granted pharmaceutical patent monopoly. One that will assure reasonable pricing. This article on Financing Drug Research offers some suggestions. Medicynic suggestions won’t cost a penny and are a good start to a new health care system:

1. Require the government and pharmaceutical companies to negotiate prices for patented medications purchased for government programs and beneficiaries. Including Medicaid, Medicare, the Federal Employee program and Tricare this would affect 100 million citizens (1/3 the population of the U.S.) Since we like transparency we should make the negotiated prices public.

2. Enforce the reasonably pricing provisions of Dole-Bayh. Retrieve the taxpayer’s contribution to drug development costs (approximately 20 billion a year to basic medical research) from patent holders and use these proceeds to defray pharmaceutical prices to consumers. This would also require the disclosure of the real development costs of pharmaceuticals.

3. Prohibit direct to consumer (DTC) advertising. In a 30 second ad full disclosure as outlined below is not possible. As a result patients do not fully understand the limits and costs of any given product. Few countries allow such advertising.

4. If we don’t wish to completely prohibit DTC advertising, require full disclosure. This would include mention of the risks of treatment and a summary of proven benefits and competing approaches in clear language that a lay person can understand. The price of the medication, with estimates of monthly and yearly costs as well as a measure of cost effectiveness (cost/unit of additional survival time or other approved measure) must be also be provided to fully inform the consumer.

5. Require clinical studies to include cost data as well as a measure of cost effectiveness (QALY-Quality adjusted life year or other) in the discussion of any phase II, III or IV study reporting positive results.

6. Monitor the FDA approval process to be certain that generics come to market quickly on patent expiration.

7. The Canadian system controls patented drug prices by not allowing marketing unless the drug is priced right. A similar program could be instituted here to decrease our pricing to the level of other industrialized countries.

8. Alternatively, link the length of patents to reasonable pricing. As part of the FDA approval process the proposed price of the new medication would be compared with similar medications already on the market and with the same medication in other countries. The same process that the Canadian patent drug review board uses. If priced a significant amount over the comparator, the patent length would be decreased by some period of time to be determined by the review process–there are many ways such a link could be structured. For unique innovative drugs the cost of development could also be factored into the pricing length of patent equation. Price increases during the duration of the patent would be tied to the rate of inflation. If they exceed that rate the patent length would be proportionally shortened.

Ten Issues that go away with a Universal Health Insurance and two that won’t

Ten issues that go away with a national health insurance system:

1. The approximately 47,000,000 uninsured: All will have access to coverage with incentives for provider efficiency and the most cost efficient interventions.

2. The profit squeeze on employers who provide health insurance to employees: It’s estimated that U.S. car makers have expenses of over $1500/car related to health care coverage for employees. A national system, delinked from employer based insurance, allows our employers to compete on the same basis as those in other industrialized countries.

3. Our disgraceful system of health care for GI’s and their families: Incorporating the VA and military health care systems is into a National Health Insurance program provides more and better options for care. These will be community based and thus provide more convenient access.

4. The administrative duplication and fraudulent behavior of multiple insurance providers, each with their own administrative overhead and fiduciary responsibility to generate profits: It’s estimated that we spend 30% of our expenditures for health on administration ($1059/capita in U.S. vs $307/capita in Canada). That could easily be halved or more with a national health program.

5. The conflict of interest between insurers, providers and patients.

6. The crisis in emergency rooms: With insurance people will have a place, other than ER’s, to go with non-emergent medical issues

7. The dance of the veils billing system: There is no set price for services. Those with leverage, i.e. large insurers, are given large discounts while the individual pays the full amount. If everyone has insurance there will be one negotiated price.

8. Big PHARMA’s free ride: We pay more for medications than any other industrialized country. PHARMA’s mantra that they need profits to encourage creativity is bogus when one considers they spend more on promotion and advertising than research. In a national insurance scheme drug price negotiation will be the rule–as it is in the rest of the industrialized world. (see more below)

9. Bankruptcy due to enormous medical bills

10. Our mediocre health care outcomes: We spend more per capita than anyone, yet our outcomes are in the middle of the pack. With universal access we can expect this to change.

None of this will be automatic and actually having an efficient functioning system of care will require much due diligence and negotiation.

What won’t change is physician unhappiness with reimbursements and the continuing issues with intellectual property rights. No where in the world are physicians as well paid as here. We’ve made the profession entrepreneurial and money driven and in the current non-system reward procedures rather than primary care. It can be anticipated that a national health insurance scheme will want to flatten the disparities and redistribute, somewhat, the fees. One would hope this would guarantee all physicians reasonable reimbursement for their time and expenses. However, meeting the expectations of the profession will be almost impossible–as it is now.

We do need some type of protection for innovators in our system. We should not however delude ourselves that this is a “free market”. Patent protection creates monopoly and in health care that has resulted in a life threatening market distortion that we can no longer afford. We need to somehow require patent holders to price their products responsibly and to be efficient in their product development and marketing. Once again meeting the expectations of the industry and their stockholders will be almost impossible–as it is now.

But in both cases the status quo is not working.

Pharmaceutical Patents–history of the problem

Drug companies claim the U.S. patent system encourages development of new drugs and that the high prices are a necessary corollary. (see this) Others have questions regarding the monopolistic practices legalized by the system. This FDA Backgrounder, and this chapter from Against Intellectual Monopoly by Michele Boldrin and David K. Levine offer more background information.

Wikipedia defines a patent as a “set of exclusive rights granted by a state to a person for a fixed period of time in exchange for the regulated, public disclosure of certain details of a device, method, process or composition of matter (substance) (known as an invention) which is new, inventive, and useful or industrially applicable.” The right to produce the product protected by the patent is subject to further regulation by various regulators.

The regulator of drug patents in the United States is the FDA. Over the years the rules governing drug patents have evolved. Some milestones include:

1938 Federal Food, Drug, and Cosmetic Act : For the first time it was required that a drug be shown safe.

1962 Kefauver-Harris Drug amendment: Required that the drug be proved effective before marketing.

1980 Dole-Bayh– Prior to this products developed under federal grants were in the public sphere. To encourage commercial development of these advances individuals and institutions were allowed to patent these developments and even license or sell the patent to private companies.

Note: Products developed to a major extent with public funds, such as imatinib (Gleevac) and bevacizumab (Avastin), are taken private and the public then gets to pay whatever the drug company or developer wishes for the technology. The result of Dole-Bayh has been medical progress at a tremendous cost. Basic research has suffered as workers are continually looking for something to take private-akin to hitting the lottery. We’re talking tens to hundreds of millions of dollars in fees to the individuals and the sponsoring university of such research. This has literally changed the landscape of medical research and not all for the better. See this article for the rationale and the unintended consequences. More here and here.

In part because of Dole-Bayh, prescription prices in the past 25 years have increased astronomically. The price of newly patented oncology medications has increased to 50-100 times the level of the seventies, 15-20 times that of the 80’s. Between 1990 and 2001 the average price of all types of prescriptions tripled. Not surprisingly drug profits, after paying all costs of development including research and drug promotion, are at the unprecedented level of 18-20 % of revenue. Some think Dole-Bayh as currently applied is a giveaway to the industry. They further maintain that the law has provisions calling for reasonable pricing of government financed inventions. It’s never been enforced.

1984 Hatch-Waxman act–extended the length of patents up to 5 years (normal patent length is 20 years) to make up for the time the drug took to be approved by the FDA. It also provides for accelerated approval of generic drugs by not requiring generic companies to repeat the original research that proved them safe and effective.

Note: Drugs that are clearly effective and safe are FDA approved and marketed promptly and do not qualify for additional patent time sanctioned by Hatch-Waxman. On the other hand many of the drugs needing additional time for approval and wanting patent extensions have marginal efficacy and/or questions regarding toxicity. That’s what delayed their approval. Ironically, the terms of Hatch-Waxman will extend patents most for drugs that may deserve it least.

The law is gamed by patent holders through legal loop holes and payments to generic manufacturers that actually delay the marketing of competing generics. It’s been a boon to lawyers. A company with a patented drug for example has been able to delay a generic by 30 months simply by raising an objection to marketing it-this was done multiple times in some instances. In addition it allowed hundreds of millions of dollars in payments between the patent holder and generic companies to delay the release of generics.

There has been some attempt to control this. The Greater Access to Affordable Pharmaceuticals law passed the Senate in 2002 and was reconsidered in 2003. The FDA revised the rules of Hatch Waxman to address this issue, but the affect of these changes remains unclear. This article from the July 1 2006 Times and this from the July 3, Washington Post indicate that the pharmaceutical industry continues to game the system.

Among the criticisms of patents in the wikipedia article is the notion that patents create monopolies which almost always result in inefficiencies, stifle competition (by definition), cause higher prices, lower quality and shortages.

It’s clear that our system of care has problems with inefficiency and pricing from the patent monopoly. We have the most costly health care system in the world but have mediocre results. Prices of pharmaceuticals have reached unprecedented
levels. Medicynic has previously noted pricing of new cancer drugs/year exceeds the median and average incomes in the U.S. and more. The issues of lower quality and shortages apply because of aggressive marketing of mediocre patented drugs and because people lack access because of price–a pernicious form of health care rationing.

Patent expiration–Zocor

Zocor’s patent has expired. The article in the Times describes the financial ramifications on statin manufacturers Merck, Pfizer, Schering Plough, and Astra Zeneca.

Statins (a common class of drugs to lower cholesterol) are big business, in case you ever doubted it. Lipitor generates revenue of 12 billion dollar a year while Zocor generates 10 billion. With profits of drug companies in the 15% of revenue area these drugs are cash cows.

Even considering the drug companies estimate of $800,000,000 (a disputed number) to develop a new drug these revenues imply excessive and remarkable profits–but that’s our system, or is it?

The drug development equation is complex with a long pipeline consisting of basic research, identification of drug candidates, testing for toxicity and efficacy and finally release on the market. Pharma, however, is rewarded with market monopoly’s for 20 years, or more; pricing that seems to have nothing to do with real development costs; and profits that are quite remarkable–see Marcia Angell’s article and book of the same name or John Abramson’s book Overdosed America (review here).