Access to Therapies: Bench to Patient to Society
David Wofsy, M.D. from the University of California - San Francisco presented a summary of the report of the American College of Rheumatology Blue Ribbon Committee on New Therapies..
This committee was commissioned in March 1999 by Bevra Hahn, M.D. (then President of the ACR) to address several significant challenges related to newly approved, expensive therapies for arthritis:
- How can we ensure access to therapy for all patients who need it?
- In a system of finite resources, what responsibility do we bear to optimize appropriate use of new (expensive) modalities?
- How can we ensure that studies are done to provide a sound scientific basis for the rational use of new (expensive) therapies?
In developing its recommendations, the Blue Ribbon Committee was guided by three basic principles:
- Patients should have access to medically-needed prescription drugs and devices.
- Whenever possible, treatment decisions should be evidence-based.
- Access to medically-needed prescription drugs and devices is a shared responsibility among patients, physicians and other health professionals, professional organizations such as the ACR, voluntary health agencies such as the Arthritis Foundation, and employers.
The Blue Ribbon Committee recommended that the ACR take the actions listed below. [No implmentation of these recommendations has been instituted yet, however.]
- Devise procedures through which the ACR can develop recommendations for the use of new therapies whose cost may limit access.
- Support efforts to strengthen Medicare.
- Compile and disseminate information regarding programs to facilitate access to therapy.
- Other recommendations are available through the ACR.
Mr. Kevin Brennan of the Arthritis Foundations Office of Public Policy and Advocacy discussed the AFs programs to advocate for Access to Therapies..
These have included the May 2000 "Message in a Bottle" campaign in which patients sent empty prescription bottles and letters, emphasizing the cost of their prescription medications, to their Congressional representatives. Another is the Arthritis Advocacy Program to encourage NIH, CDC, and other government groups to increase their funding of arthritis research.
There have been several government-based proposals to try and deal with the lack of prescription coverage for seniors - although none were adopted. For example, a Presidential Commission under Clinton recommended a system similar to that of the Federal Employees benefits program in which patients/enrollees choose from a menu of benefits, one of which is a prescription drug plan. Alternatively, Republicans have proposed tax cut vouchers as a mechanism for purchase of prescription drugs. The Arthritis Foundation will monitor all plans moving through Congress to evaluate how each will impact on patients with arthritis and coverage for their arthritis medications. For more information on public policy initiatives, call the Arthritis Foundations Office of Public Policy and Advocacy at (202) 537-5471.
Dorothy McCabe, Ph.D. of Amgen, Inc discusses Cost of New Development of New RA Drugs.
Dr. McCabe stated that spending for research and development by pharmaceutical companies has increased by 14% since 1975, and is now at $24 billion. New technologies such as pharmacogenomics, combinatorial chemistry, biologic treatments, and a shift in focus by the pharmaceutical industry to chronic diseases like rheumatoid arthritis (RA) and cancer have contributed substantially to additional costs.
Nine to nineteen years are required to move a drug from bench research through clinical research to FDA approval. Validation of a prime candidate drug is completed in one to two years of basic research. In the pre-clinical phase four to five candidates may be studied. However, only one prime candidate will be chosen for further research and development due to the expense involved in the use of animals, animal facilities, and staff. Once safety and efficacy are established in animal models, research proceeds to the most costly phase of development - that is, clinical development in humans. FDA approval now requires data from thousands of patients over a one to three year period from phases I, II, III. In addition, phase IV studies are now necessary in order to obtain additional safety data required by the FDA to assess long term risk. Previously, studies were completed in twenty-four week periods for each of the clinical study phases. Furthermore, additional assessments, which include x-rays, magnetic resonance imaging (MRI), and bone marker analysis, are also essential to further establish clinical efficacy of a new drug for RA.
Thus, a single drug compound can cost $200-300 million from its original concept to FDA approval following establishment of safety and clinical efficacy. However if the cost of failure is included, the cost increases to $600-900 million. The time, the advent of new technologies to assess safety and clinical efficacy, and the extensive staff involved have all contributed significantly to the increased expense required for a new RA drug treatment to become available to the public. Some questions were raised by the audience as to the true validity of some of these costs.
David Henry, M.D., Director of the WHO Collaborating Centre for Training in Pharmacology and Rational Drug Use, at the University of Newcastle, NSW, Australia discussed Drug Reimbursement.
The rising costs of new drugs is stressing many health care funding programs, and many governments are exploring different approaches to cost control of new drugs. Worldwide there is a rising tide of concern about the pricing of new drugs, and the profitabililty of the multinational companies that produce them. Unlike other products of technology-based industries (for instance, computers), medicinal drugs have become a "sellers market" with some new products offering only marginal benefits yet at much higher prices than the agents they replace. Consequently, the pharmaceutical industry has enjoyed a period of unparalleled profitability and influence.
It will be difficult, however, for the industry to sustain recent levels of growth in the face of increasing criticism around the world. Pharmaco-economics-based reimbursement programs have been adopted in a number of countries, including Australia, Canada, United Kingdom, Netherlands, Italy, Portugal, Sweden, Norway and Finland. The industry has responded with legal challenges to governments and advisory bodies in some countries. In developing countries, it is claimed that the relentless pursuit of intellectual property rights has denied the rights of local manufacturers to produce much needed (cheaper) generic forms of currently patented drugs. The health needs of these countries are seen to be neglected (e.g., access to antiretroviral drugs for HIV patients).
Dr. Henry proposed potential solutions or responses to this situation:
- Compulsory licensing
- Parallel importing
- Tiered pricing (sell more cheaply to developing countries-- this is starting to happen)
- "South-South" collaborations - e.g., South Africa and Brazil manufacture drugs at reduced cost and exchange between themselves
- Donations - e.g., Bill Gates
- International non-profit manufacturers
- Use of pharmaco-economic analysis to restore balance in the market
Conclusions:
- Dr. Henry noted that industry has indeed accepted that access to new therapies must be improved. The question is how to do it while protecting the rights and (some) profitability of manufacturers.
- The most popular stance internationally is for differential pricing to developed and developing countries.
- The main threat to the pharma industry is loss of patent protection.
- He proposes that pricing should be based on pharmaco-economics not on developmental costs since the latter is often grossly inflated (in large part due to marketing).
Drummond Rennie, M.D. of the Institutes of Health Policy Studies at University of California, San Francisco discussed The Reporting of Pharmaco-Economic Analysis.
Patients, health management organizations, and governments want to pay only for those drugs that are most cost-effective. However, cost-effectiveness analyses of drugs have a poor reputation among medical journal editors (Dr. Rennie is former editor of the Journal of the American Medical Association, JAMA). This is because such analyses are often based on suspect trials, on suspect models and on suspect assumptions, perhaps because such analyses are often done at the behest of marketing departments, and are controlled from start to finish to ensure a result favorable to the marketers products. The critics ability to know what went into the analyses is often severely limited. There are ways to improve the process, from the registration of all phase III trials at inception, to putting all the supporting material on the Web for open examination. Manufacturers should sponsor only those studies that allow full examination of all data. In addition, the scientists and clinicians involved in these trials should earn the public trust, and avoid situations of conflict-of-interest. Science does not exist until it is published because only then can it be critically analyzed. The science is only believable if the data and the investigators can be trusted.
