Ten million people die each year from diseases that have available cures. Tragically, the essential medicines to treat such diseases are lacking throughout much of the world. Nearly a third of humanity does not have regular access to essential medicines, and in the poorest parts of Africa and Asia this figure rises to over 50%. During the fifteen seconds it takes to read this paragraph, five people have died from preventable causes.
Many diseases affecting millions of the world’s poorest remain entirely overlooked. Countless people suffer in developing countries from sleeping sickness, lymphatic filariasis, blinding trachoma, and other “neglected diseases,” because these destitute sick do not constitute a sufficient market opportunity to attract commercial research and development. In fact, only 10% of research and development (R&D) dollars go towards research into 90% of the world’s health problems.
The health burden facing millions in the developing world is of the most pressing moral issues of our time, yet also one of the most solvable. In this environment, universities have a critical role to play. Many of our most important medicines were invented at universities; their accessibility around the world depends critically on how universities manage their intellectual property. As research institutions that exist to serve the public good, universities are natural leaders in the search for new treatments for neglected diseases.
Watch UAEMer Mike Gretes speaking about UAEM’s ideas at a TEDxTalks event at UBC in 2008:
Medical research and development (R&D) is undoubtedly an unpredictable, lengthy and expensive process. There are many entities involved, including universities, non-governmental organizations, governmental organizations, and pharmaceutical companies.Research & Development
Research & Development
Medical R&D begins with basic research on the disease itself. Basic research seeks to understand the biology of a specific disease, down to the molecular level. This research is unpredictable and potentially never-ending, due to the immense complexity of the human body and disease processes. Any given scientist may spend decades on research with no obvious direct impact on health care; but with many people working together, useful knowledge is gradually assembled.
Once a sufficient level of understanding of the disease is reached, screening of potential compounds that would affect the disease may begin. Through computer simulation or manual trial-and-error, scientists search through extensive compound libraries and to seek those that might affect the biology, and therefore the outcome, of the disease, and that might feasibly and safely be given to people.
The most promising compounds then proceed to preclinical trials. Further tests are carried out in test tubes (in vitro), as well as in animals (in vivo). The goal is to further determine whether the drug might really be effective, what doses might be safe, and what negative side effects might occur.
If the drug still appears to be safe and effective, testers then request regulatory approval to conduct clinical trials: that is, trials in humans.
In phase I, an initial assessment of safety, a small study group of about 100 healthy subjects are issued the compound. Doses are administered in an increasingly concentrated fashion to determine any ill effects on healthy subjects.
In phase II, an initial assessment of efficacy, 100 to 500 subjects are enlisted who actually have the disease of interest. Patients are carefully monitored to determine the drug’s impact on the true disease.
In phase III, long-term effects are assessed in 1000 to 4000 patients. This is the longest stage.
Marketing and surveillance
Finally, the tester submits all the evidence gathered so far to regulatory authorities. If approved, the drug is now allowed to be marketed. To be approved a drug must be useful to treat a given disease, and cause minimal harm. In addition, its labelling must be accurate and non-deceiving, and the production processes must be reliable.
Once marketing begins, the drug must simultaneously go through phase IV, in which the drug, now that it is being used in practice, is monitored for rarer or very long-term side effects.
Patents give their owners exclusive rights to the production, use, or sale of a product. We grant these rights (usually for 20 years) to inventors when their invention is new, useful, and not obvious. These rights can be transferred or shared at the owner’s discretion.
The idea is that patents allow their owners to charge higher prices than they could get if everyone was allowed to sell their product. Product development can be an expensive process, so this provides an important economic incentive to develop new useful products. Ultimately, innovation is paid for by those who buy the new product at the elevated price.
There are two major weaknesses to this approach to funding innovation:
- Anyone who can’t afford the asking price will be unable to access the product, even if the asking price is higher than the actual manufacturing price.
- Other inventors must pay a premium to use this new product in their research, or may not be allowed to use it at all, so further innovation is hampered or outright blocked.
Of course, if the product in question is a life-saving medication, the world’s approach to innovation is a matter of life or death for millions of people.
International agreements on patent law
Patents apply only within countries, not internationally: you must register a patent in every country where you want to control your invention. Each country implements its own set of patent laws, but it is constrained by any international agreements it has signed.
Countries that are members of the World Trade Organization (WTO)—which is most countries—must respect a number of multilateral trade agreements. The agreement governing patent law is called the Trade-Related aspects of Intellectual Property rightS (TRIPS) agreement. TRIPS requires a minimum of 20 years of patent protection for any new, useful, and non-obvious product, including medicines. Precise meanings of “new”, “useful”, and “non-obvious” are not made explicit in the agreement: each country gets to interpret these terms as it sees fit. TRIPS came into force in 1995, and member countries whose patent law did not meet the agreement at that time were given ten years to revise their laws (e.g. India: see our case studies).
Many countries have also entered additional bilateral trade agreements; these often require stronger legal protection for patents than TRIPS does.
Patents and access to medicines
TRIPS allows countries to override patents in times of national emergency, and for public non-commercial use. (Again, “emergency” is up to each country to define for themselves.) The mechanism by which a country overrides a patent is called acompulsory license: effectively, the government grants someone else the right to also manufacture, sell, or use the patented technology, so that the primary patent-holder no longer has a monopoly. The market becomes competitive, so prices fall.
For many technologies, these flexibilities may not be necessary, but they have received a great deal of attention for the case of medicines, due to the potential impact on public health. When TRIPS was first adopted, the intent of the flexibilities had not been made entirely clear, and countries were wary of actually using them, fearing negative repercussions from their trading partners.
WTO members therefore clarified the intent of the flexibilities—including the freedom to issue compulsory licenses—in the Doha Declaration of November 2001, which said:
“[TRIPS] can and should be interpreted and implemented in a manner supportive of WTO members’ right to protect public health and, in particular, to promote access to medicines for all“.
Some countries have since taken advantage of compulsory licensing (e.g. Brazil and Thailand: see our case studies). However, compulsory licenses are only useful in countries with a domestic pharmaceutical manufacturing industry—i.e. in relatively wealthy countries.
The poorest countries, on the other hand, do not have the resources to produce their own medicines, so they must import all their medicines from wealthier countries. Patents governing drug manufacturing are therefore beyond their control. And even if the governments of manufacturing countries wanted to override patents in order to export cheaper drugs, the original TRIPS agreement only allowed compulsory licensing for national emergencies—not international ones. The WTO attempted to resolve this problem with its August 30 2003 decision. This allows manufacturing countries to issue compulsory licenses to export drugs to countries that cannot produce them, even while the drug remains patent-protected for domestic use in the manufacturing country.
Over 30 countries have since incorporated this new flexibility into their patent laws. However, as of June 2009, this flexibility has only been used once (by Canada and Rwanda: see our case studies).
Patenting by universities
30 years ago, university research culture in North America generally focused on pure discovery, and university researchers did not seek to commercialize their results. Any patents generated through publicly-funded research were the property of the funding agency. With nobody in particular standing to benefit from further development of technologies, many promising ideas went unpursued.
With the intent of spurring on the development of these technologies, in the US, the Bayh-Dole Act was adopted in 1980, which granted patent rights on federally-funded research to the funding recipient (i.e. the university), and not the funding agency. Commercialization and patenting of new technologies by universities have grown dramatically ever since.
(In Canada, there is no such explicit law, but Canadian federal funding agencies have adopted a similar policy: patent ownership is left up to the institution receiving the funding. At most Canadian univeristies, the researcher controls the patent, but the university provides services to help them commercialize their invention. One exception is UBC, which operates more like most American universities, in that the university controls the patent.)
What does this have to do with UAEM?
This is the context in which our work takes place. The principal focus of our work, as regards access to medicines, has been trying to convince universities to use their positions as patent-holders within this system to secure greater access to new technologies for the poor, while still maintaining the economic viability of innovation. It is important that we understand how such changes might play out within the existing system. In addition, as our group has grown, we have moved into advocacy around changing the international legal framework as well, including at the levels of national law and international agreements.
These very readable documents cover similar material, but in greater depth.
- Drug patents under the spotlight: Sharing practical knowledge about pharmaceutical patents. Médecins Sans Frontières, May 2003. http://www.who.int/entity/3by5/en/patents_2003.pdf.
- Commission on Intellectual Property Rights final report. Chapter 2: Health. UK, September 2002.http://www.iprcommission.org/graphic/documents/final_report.htm.
The research gap
Many diseases affecting millions of the world’s poorest remain largely overlooked: countless people suffer in developing countries from sleeping sickness, lymphatic filariasis, blinding trachoma, and other “neglected diseases.” Many of these diseases have no safe and effective treatments, because these destitute sick do not constitute a sufficient market opportunity to attract commercial research and development (R&D). In fact, only 10% of R&D dollars go towards research into 90% of the world’s health problems.
- “NTDs: Diseases of the Bottom Billion“, by Karolina Maciag, Jason Zhang (December 2010).
- “The Global Health Crisis and Our Nation’s Research Universities“, by Sandeep P. Kishore, Gloria Tavera, Peter J. Hotez (February 23, 2010).
- “Rapid-Impact Interventions”: How a Policy of Integrated Control for Africa’s Neglected Tropical Diseases Could Benefit the Poor, by David H. Molyneux, Peter J. Hotez, Alan Fenwick, PLoS Medicine (November 2005).
The access gap
Essential medicines are drugs and vaccines that the World Health Organization considers necessary for a basic health care system1. The list of essential medicines includes drugs for the treatment of HIV, malaria and tuberculosis, but also non-communicable diseases such as diabetes, cancer and cardiovascular disease.
One third of the world’s population lacks access to these medicines2. The consequence of this problem is commonly referred to as the access gap: 10 million people die annually from diseases that are treatable with current medicines.3
The reasons for the lack of access to medicines are diverse: high prices, lack of infrastructure (e.g. refrigerated storage for drugs, transportation to the clinic, clean water), medical staff, and a lack of political will. UAEM (Universities Allied for Essential Medicines) focuses on eliminating the high price barrier to accessing needed medicines including, but not limited to, the WHO list.
Why are prices high?
The reasons contributing to the high prices of medicines are complex. Over the past several decades, pharmaceutical and biomedical industries have made tremendous strides in terms of producing an unprecedented variety of effective drugs. However, as the ambitions of researchers grow in their quest to conquer disease, so too has the cost of research grown. From the birth of a new drug in the discovery phase at universities and long-term development at research firms, drugs require stringent testing in order to ensure both safety and efficacy before they are ready for use by the general public. Healthcare economists have recently estimated that for each drug developed, it costs firms approximately $802m USD in order to bring to market; this includes the expenses associated with failed drugs as well.
In order to make it economically feasible for private companies to develop these medicines, countries grant patents on new therapeutics. A patent is an exclusive right to manufacture and sell a product in the country the patent was issued in. This exclusivity enables the owner of a patent to recoup the money spent on research and development, by setting the maximum price that they expect the market can absorb—often it is much more than the actual manufacturing cost. Unfortunately, since
new medicines are typically sold at such a high price, access is limited to the select, few wealthy countries and the individuals who can afford to pay these prices.
What role does my university have?
Private research firms are not the only engine of biomedical R&D. Many drugs are initially discovered as new chemical entities (NCEs) at public universities.
A researcher at a university who discovers a molecule that may become an effective drug files a patent on that molecule. Since universities do not have the capacity to develop and distribute drugs to market—due to the costs associated with testing and mass production—they license the patented technology to a pharmaceutical or biomedical firm, transferring the patent rights to the licensee. Most universities have a special department called a technology transfer office (TTO) that negotiates the business and legal agreements between the researcher and the licensee. Transferring the patent rights allows the company to exclusively manufacture and sell the drug to people who can afford it. Some of the profit returns to the university as royalty revenue.
However, the typically high prices set by manufacturers frequently put most life-saving drugs out of the reach of the poor. For instance, treatment of HIV-positive patients with a triple-drug cocktail containing the antiretroviral drug Stavudine (Zerit), developed at Yale and then licensed to Bristol-Myers-Squibb, cost $10,439 a year in 20024. For individuals who live on just a few dollars per day, this expense is impossible and the prices set by firms no longer justifiable.
How can my university change?
We at UAEM propose that the university simultaneously license the drug to generic companies, who are able to produce the drug for people living in low- and middle-income countries, at a lower, more affordable price. Under these provisions, brand name pharmaceutical companies can still earn profits selling to high income countries, while generic producers ensure access in low and middle-income countries.
The price of Stavudine, for instance, decreased more than 100-fold, to $87 per patient per year5, after student activists and the humanitarian organization Médecins Sans Frontières successfully pressured Yale University and Bristol-Myers Squibb (the patent holder and license partner) to allow generic production. UAEM believes that the increased production and availability of generic medicines is one of the keys to solving the current access crisis. For more information about the importance of generic drug manufacturing, please visit www.avert.org/generic.htm.
A question often asked is, “Won’t parallel importation hurt the profits of pharmaceutical companies and of universities?” (Parallel importation is also known as drug diversion, and refers to the selling of generically produced drugs intended for low and middle-income countries, in high-income countries, where pharmaceutical companies still hold patents). Research has shown that this is not a significant concern.6
UAEM members are committed to the idea that preventable deaths due to lack of medication is a problem that can be solved in our generation. UAEM calls on universities to recognize their role as public institutions created to serve the public good, to support those in need by implementing global access provisions, and to use their rights as patent holders and ensure that prices remain within reach of people regardless of where they live or how much money they earn. The University of California at Berkeley, the University of British Columbia, and Emory University have already adopted socially responsible licensing policies and with your help, we can ensure that your university follows suit!
1. Chokshi DA (2006) Improving access to medicines in poor countries: The role of universities. PLoS Med 3(6): e136. DOI: 10.1371/journal. pmed.0030136
This is one of the first scholarly articles published about UAEM, in the open-access journal Public Library of Science (PLoS). It describes both the access gap and the research gap (referring to a lack of research into treatments for neglected diseases) and is an excellent starting point for new members to familiarize themselves with the issues.
2. Kapczynski A, Crone ET, Merson M (2003) Global health and university patents. Science 301: 1629.
This editorial in the journal Science describes licensing and patenting strategies universities may use to ensure that people living in low and middle-income countries have access to their inventions. It also addresses concerns about possible decreased revenue to universities.
3. Idea #5: Cheap Meds for the World’s Poor. The Tyee. http://thetyee.ca/News/2007/12/21/CheapMeds/.
This article introduces the topic of affordable access to essential medicines and describes the successes of the UAEM chapter at the University of British Columbia, which has recently adopted a set of principles of global access to UBC technologies, which include drugs, biologics and any other health-care related tool.
2. Habiyambere V. Progress of WHO Member States in developing national drug policies and in revising essential drugs lists (WHO/DAP/98.7). World Health Organization: Geneva, 1998.http://www.who.int/medicines/publications/essentialmedicines/en/.
4. Untangling the web of antiretroviral price reductions. Médecins Sans Frontières. http://www.msfaccess.org/main/hiv-aids/untangling-the-web-of-antiretroviral-price-reductions-11th-edition/.
5. DiMasi, Hansen, Grabowski (2003) “The price of innovation: new estimates of drug development costs,” Journal of Health Economics; Vol 22, pp. 151-185.
6. Journal of the Association of University Technology Managers, Volume XVIII Number 2 – Fall 2006, pp. 29-37.
These are some key documents regarding the issues we tackle:
- Médecins Sans Frontières. Untangling the web of antiretroviral price reductions.
- A Stevens, A Effort. Using academic license agreements to promote global social responsibility. LES Nouvelles 43(2):85-101, 2008 June.
- The George Institute for International Health. G-FINDER: Global Funding of Innovation for Neglected Diseases. 2009 Dec 15.
- Médecins Sans Frontières. Giving developing countries the best shot: An overview of vaccine access and R&D. 2010 May 10.
- Knowledge Ecology International (KEI) — the definitive database of all things related to IP and health
- Médecins Sans Frontières (MSF)’s Access to Essential Medicines Campaign
- Access and Delivery of Essential Medicines (Stanford) — watch lectures online!
- Designing Strategies for Neglected Disease Research (Amy Kapczynski, Berkeley)
- Increasing Access to Essential Medicines in Developing Countries: Strategies and Barriers (Sonja Babovic, UBC)