Last week, the American College of Physicians (ACP), a 129,000-member group of internal medicine physicians, and second-largest doctors group in the US, called for increased FDA authority and  funding to help protect  consumers from the risks of newly-approved prescription drugs.  Their six recommendations were:

1) increased funding for FDA staff and technological capability to keep pace with the increased workload due to the number and scientific complexity of new products submitted for pre-approval, globalization, and emerging safety challenges.

2) increased FDA authority and capacity to regulate drugs manufactured outside the US;

3) expanded FDA authority and involvement in the design of clinical trials to better evaluate safety and efficacy, through longer trials with larger, more representative target populations;

4) a ban on clinical studies of ‘bundled’ drug products that reduce access to drugs;

5) Improvements that increase  reporting of adverse events by doctors and others; and

6) limits on direct-to-consumer advertising in the first 2 years a drug is on the market.  

Increased FDA funding:

The ACP report notes that FDA’s “ability to approve and monitor new drugs has been compromised by chronic underfunding, limited regulatory authority, and insufficient organizational structure.” ACP recommends that FDA funding is increased, to improve their “ability to approve and monitor prescription drugs….”

 Regulating drug manufacturing overseas:

The ACP should be praised for bringing attention to severe under resourcing at FDA, particularly as it affects the Agency’s ability to ensure the safety of drugs manufactured overseas. Today’s globalized pharmaceutical supply chain has rapidly outgrown FDAs capacity, and FDA is not able to inspect foreign sites with any meaningful frequency. A 2008 GAO study found it would take FDA 13 years to inspect each foreign manufacturing establishment once, while domestic sites are inspected on average every 2.7 years.

 ACP points out that a provision for increased foreign inspections were included in a bill (H.R.759) introduced by Reps. Dingell, Pallone and Stupak in January this year. A similar bill (S.882) championed by the late Senator Kennedy and Senator Grassley also seeks to increase foreign site inspections by FDA. Both bills establish new industry user fees to pay for this expanded oversight, but also require annual increases in other appropriations to ensure sustainability. ACP importantly indicates that both types of financial support are needed, and mentions a number of other key provisions in the House bill, including a requirement for dedicated foreign inspection staff.

Facilitating increased physician reporting of adverse events:

The ACP also recommends FDA pursue efforts to “educate physicians on how and when to report an event that is potentially drug-related.” They also proposed streamlining the reporting systems and ensuring anonymity to “facilitate reporting by health professionals.”

DTC advertising of new drugs:

The report acknowledges that direct-to-consumer (DTC) advertising can “dramatically increase [use] of a new drug and … may expose large numbers of people to a drug with undocumented safety concerns.”

The best example of this concerns was seen in the  rapid use of the  pain-killer Vioxx upon hitting the market. The aggressive DTC advertising and other promotional activities  by manufacturer Merck lead to Vioxx’s use by over 20 million consumers, which then lead to  88,000-139,000 cardiac events, and  an estimated 35,000-55,000 deaths.  Adverse reactions and safety concerns arose with the  drugs Zyprexa and Bextra, among many others 

To address this concern, ACP recommended that FDA ‘limit’ the DTC advertising of newly approved prescription drugs, and require that labels and ads indicate that data related to the new drug’s “risks and benefits … are less extensive than those [for older] products…”

 Prohibiting clinical trials of ‘bundled’ products:

In addition, ACP also makes a recommendation that would help FDA avoid placing itself in the position of helping drug manufacturers introduce ‘bundled’ or combination drug products designed to protect a drug from generic competitors. 

For example, the report describes how, in 2005, the drug manufacturer “Pfizer submitted plans to the FDA to begin conducting large trials to test the cholesterol drug torcetrapib in combination with the popular and widely used statin Lipitor.”  By allowing clinical trials of the ‘combination drug’ rather than just torcetrapib alone, approval of the new combination drug product would insulate Lipitor from competition. This then puts FDA, in approving the study design, in the awkward position of helping the drug manufacturer avoid anti-trust prohibitions, the report said.

This concern is similar to the claims in the PAL member lawsuit on the drug Norvir, where drug manufacturer Abbott Labs bundle their HIV protease inhibitor cocktail drug Norvir in a new bundled-product-drug Kaletra, in order to increase market share.

ACP recommends that FDA not approve clinical trials which seem to be designed to ‘bundle’ a new drug with an existing brand name drug, and thus perpetuate the patent-protected sales of the new combination product.

To read the full report, visit http://www.acponline.org/advocacy/where_we_stand/policy/fda.pdf

Dean Baker, from the Center for Economic and Policy Research, has a great piece up on truthout.org called Firefighters and Prescription Drugs. Baker has frequently written in the past on the perversity of our current patent-based system for developing new drugs, and what alternatives there are. (See, for example, Financing Drug Research: What Are the Issues?)

Baker’s main point is that we have accepted the current system of using the incentive of a patent to spur research and development as inevitable and natural. It brings to mind the saying “the fish are the last ones to notice the water.” It’s vital to remember that there’s nothing natural or inherent about that system, however.

This is the system that has brought us more than 8 prescription drugs for heartburn, and more than 4 for erectile dysfunction, but no meaningful new treatments for diseases that are true scourges of humanity, like malaria and tuberculosis. Other systems might work much better at creating incentives to develop treatments, particularly for these neglected diseases that affect millions of people who happen to have the rotten luck to live in poor countries rather than in the U.S. where TV ads work to convince us all that we have restless leg syndrome, insomnia, and toenail fungus.

It’s telling that although all of the presidential candidates have talked about the greed of pharmaceutical companies, none have even dared to mention, let alone question, the conventional wisdom about how we develop drugs.

Baker offers a variety of proposals, such as increasing the budget for the National Institutes of Health, running all clinical trials through the NIH, etc. Publicly-funded medical research has a vital role to play — and we need to make sure that we don’t pay twice for drugs and medical treatments that are developed with public funds — once when we pay for the research, and again when we are forced to pay exorbitant prices for the drugs that result from that research. The discovery of Abbott Laboratories’ [NYSE:ABT] HIV/AIDS drug Norvir was made possible by an NIH research grant, yet that didn’t stop Abbott from quintupling the price of the drug. [PAL member SEIU Health & Welfare Fund is a plaintiff in an ongoing class action lawsuit against Abbott for this price increase. See more about that case here.)

Some highlights of the truthout.org piece:

The most remarkable part of this story is we do not even have a public debate on how we finance drug research. The United States is currently spending almost $250 billion a year for prescription drugs. If drugs were sold in a competitive market, without government-imposed patent monopolies, we could save close to $200 billion a year. The $200 billion in higher drug prices buys a bit less than $25 billion a year in pharmaceutical research, according to the Congressional Budget Office. Paying $8 in higher drug prices for $1 in research does not seem like a very good deal.

Furthermore, as economists who don’t work for the drug companies will tell you, the huge markups created by patent monopolies are an invitation to corruption. When a drug company can sell a drug for $500 that costs it $4 to manufacture and distribute, it has an enormous incentive to mislead doctors and the public about the safety and effectiveness of the drug. And, when the drug company performs the research on the drug, and controls the dissemination of research findings, they also have the ability to act on this incentive.

Under the current system, we should not be surprised to find drug companies conceal evidence that their drugs might be ineffective or even harmful. Given the structure of the incentives that the government has created, we should be surprised if drug companies are not dishonest.

There are many different alternatives to patent monopolies for financing drug research. In fact, the US government already spends $30 billion a year on biomedical research through the National Institutes of Health. Virtually everyone, including the drug companies, agrees this government-funded research has been extremely valuable…

We should be having a serious national debate on the relative efficiency of the current patent system and various alternative mechanisms for financing drug research. Unfortunately, the drug companies are so powerful that few politicians are even willing to consider alternatives. In fact, the drug companies are so powerful that few media outlets would even print a column suggesting alternatives. In fact, the drug companies are so powerful that few economists would ever consider researching alternative mechanisms.

To read the full piece, go here

Hat Tip: Suddenly Senior

Dearest Readers: From time to time, it is our pleasure to bring you posts here on the Prescription Access Litigation blog written by guest bloggers. Our latest guest blog entry is by Sarah Rimmington of the consumer advocacy group Essential Action.

It’s safe to say that most Americans are blissfully unaware of negotiations that just recently went on at the World Health Organization (WHO) in Geneva to address how pharmaceutical research & development (R&D) can benefit the literally billions of people in developing countries who lack the resources (money) to pay for prescription drugs that in many cases cost more for a single pill than many of those people earn in a day, or even longer. The issue has been conveniently ignored by the mainstream media in the United States, despite the role that American drug companies play in opposing an agenda that would bring access to medicines to many of the world’s poorest people.

We here at the Prescription Access Litigation blog tend to cover only prescription drug issues here in the U.S. (and there’s plenty to cover just in this country, mind you). But occasionally we want to use our modest blog to call attention to issues outside the borders of the U.S. The pharmaceutical market has become truly a global market, with more and more clinical trials being conducted abroad, and more and more of our drugs being produced abroad, so we here in the U.S. couldn’t ignore these global issues even if we wanted to.

Without further ado, let me turn to Sarah Rimmington, for her report on the WHO’s recent negotiations and what they mean for the issue of access to medicines for the developing world:

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On May 3, representatives of more than 100 nations finished what was supposed to be the final round of talks at the World Health Organization (WHO) in Geneva. These talks were meant to spur a medical research and development (R&D) system that works for the developing world.

The WHO Intergovernmental Working Group on Public Health, Innovation and Intellectual Property (IGWG) was set up in 2006 to develop a plan to promote new medical research and development (R&D) mechanisms to serve the twin goals of promoting innovation to meet the particular needs of developing countries, and ensuring that important medicines are accessible to people in the developing world, regardless of their income.

Despite difficult and incomplete negotiations, delegates to the IGWG took an important first step by agreeing to explore some common sense measures to promote developing country-focused innovation that does not compromise access to medicines.

Patent monopolies result in high prices
Why are R&D incentives that promote innovation plus access (“I plus A”) so important? The current patent monopoly-based system of R&D has proven inefficient at advancing a needs-driven public health agenda. This is true for rich countries as well as poor, but the situation is much worse in poor countries. This has nothing to do with the ethics of Big Pharma. It is how the system is designed. (For more information on the challenges faced by developing countries under the current R&D system, refer to this report.

The current corporate sector system of R&D is driven by the prize offering of a patent monopoly. Patents are not worth much if they offer monopolies on sales to a population that — no matter how large — has little buying power. And if the prize incentive is too small, it will not induce R&D, no matter how much it may be needed as a public health matter.

Here’s what this means in practice: Developing countries comprise 80 percent of the world’s population but amount to only 13 percent of the global market for medical products. A review by Doctors Without Borders of new drugs introduced between 1975 and 2004 found that of 1,556 new drugs put on the market, only 21 were for “neglected diseases” — diseases endemic to developing countries

It is also the case that the products developed to treat diseases that occur in all countries whether rich or poor (such as cancer, heart disease and HIV/AIDS) are often not appropriate for conditions in developing countries. For example, not enough R&D is invested in creating products that do not require refrigeration, an important feature for products to be used in countries with warm climates and unreliable electricity.

The value of the patent monopoly is based on the holder using it to profit maximize as a monopolist. It is therefore no surprise that companies holding patent monopolies charge high prices. This is what the patent enables. High prices are an increasing problem in rich, developed countries, but the brand-name pharmaceutical industry’s current pricing model — which commonly runs into the thousands of dollars a year for a single medicine, and may involve charges of more than $100,000 — leaves new medicines completely out of reach of the vast majority in developing countries.

Spurring developing country-focused innovation plus access
The WHO IGWG was set up to create a global strategy and plan of action focused on advancing developing country-focused innovation that also ensures the fruits of the innovative process are available to the people that need them.

Public health experts and advocates encouraged IGWG delegates to embrace this mandate and examine systemic approaches to support R&D that do not rely on patent monopolies or the prospect of charging high drug prices as a reward, and to identify mechanisms to make the fruits of R&D widely accessible. See statements by Essential Action and Doctors without Borders.

There are a lot of good ideas, large and small, about how to do this. Notably at the IGWG talks that ended on May 3, Bolivia and Barbados put forward a series of concrete proposals for non-patent prizes to incentivize R&D, with the resulting products to be made immediately available in generic form at competitive prices. The prize proposals focus on incentivizing several priority health needs of developing countries, such as the development of a diagnostic test for tuberculosis, new treatments for Chagas disease, and priority medicines and vaccines. The countries were hoping that the final strategy that came out of the negotiations would reference the proposals as examples of the types of initiatives that countries should examine when implementing new R&D strategies for developing countries.

There is no guarantee that these types of prize funds would work in creating innovation where now there is none or much too little. But they are interesting and provocative proposals that, in keeping with the mandate of the WHO talks, concentrate on health problems specific to developing countries.

Progress and setbacks in Geneva; one more year for bold action on R&D
The good news out of Geneva is that countries came to consensus on several important issues. These include an agreement to explore R&D incentives like prizes, and to encourage future discussions of an R&D Treaty, which would involve agreement that all countries should have to contribute to global R&D, or at least participate in the R&D system, but that there should be differential obligations based on degrees of wealth.

The bad news out of Geneva is that despite this progress, much work remains to be done to promote R&D models that will work for the developing world. IGWG delegates did agree to create a working group on financing for R&D. But one concern is that the draft strategy does not specifically reference the importance of examining the Bolivia and Barbados proposals — as well as proposals that may be developed by other countries – and that the new working group will not look at such proposals.

Another concern is that because of resistance from developed countries such as the United States, the EU, and Canada, consensus was not reached on concrete proposals to actually implement the urgently needed new incentive mechanisms. A significant amount of negotiating time was lost debating core principles such as the role of patents in creating barriers to access to medicines, and the importance of promoting the use of already-agreed to flexibilities available under international trade law to promote access to affordable generic medicines where patent protections remain a problem. A number of these issues remain unresolved and will be the subject of further talks, to take place at a later date and concluded by May 2009. For more information on the recently concluded talks see comments from Doctors without Borders and Knowledge Ecology International.

Of course, it is hard not to wonder if pressure from the brand-name pharmaceutical industry – which is based in rich countries and which along with its allies remains ideologically committed to opposing any tinkering with patent monopolies – influenced the disappointing outcomes at IGWG. Industry is concerned that tinkering in the case of health problems related to developing countries will eventually threaten the patent monopoly system in the rich world, or interfere with its ability to expand sales to the wealthy in middle-income countries.

But it’s not too late. WHO member countries have another year to finalize the R&D agreement that comes out of the IGWG process; they must be encouraged to use this time wisely by taking concrete steps to advance experiments with new institutional arrangements to promote the complementary public health objectives of innovation and access. It is time to ignore those who would subordinate public health to patent veneration or commercial concerns, and enact bold solutions that have the potential to benefit us all.

For more information on the World Health Organization R&D talks see:

• An article on the recent conclusion of the talks
• Knowledge Ecology International’s IGWG webpage, which has links to key resources on this topic
• The WHO IGWG page
• The most recent version of the WHO IGWG global strategy and plan of action