E-DRUG: Donated Drugs for Public Health

[Essential Drugs Project <edp@gn.apc.org>]

E-DRUG: Donated Drugs for Public Health
---------------------------------------

Recently the Harvard Public Health Review published a long article on the
subject of donations of drugs for specific public health and disease
eradication programmes.  This may be of interest to E-DRUG subscribers, as
it deals with an important and little discussed aspect of donations.  

Philippa Saunders


>
>Attached is a text-only, email-ready version of the "Pharmacophilanthropy"
>article that appeared in the summer Harvard Public Health Review, which you
>requested for sending on to an email mailing list (e-drug).  I apologize
>for the delay in getting it out to you.  Thanks very much for your patience.
>
>Sincerely,
>
>Alexandra Benis
>
>
>Attachment Converted: "C:\Users\MAIL\SMR 99 WEB PHARMACO_FT2.txt"
>
>Alexandra Benis
>Senior Writer
>Harvard School of Public Health
>116 Huntington Avenue, 9th Fl.
>Boston, MA 02116
>617-351-0132, fax 617-351-0106
>email abenis@hsph.harvard.edu

-- 

The following article appeared in the Harvard Public Health Review, Summer=
 1999, p.32-39, Copyright 1999.  The Review is published biannually by the=
 Harvard School of Public Health, Boston, MA. Letters to the editor or=
 requests for copies should be made to the Communications Office, Harvard=
 School of Public Health, 116 Huntington Avenue, Boston, MA 02116.


Pharmacophilanthropy
By Peter Wehrwein

Just think of the lives it could salvage or save. Here was a drug,=
 praziquantel, that worked against all five species of schistosome worms. It=
 showed higher efficacy, lower toxicity, and easier administration than=
 existing drugs. And molluscicides to kill the snails that harbor and spread=
 the disease-causing parasite can only be used in geographically limited=
 areas due to cost and delivery problems. Meanwhile, schistosomiasis racks=
 up the kind of grim statistics that put it second only to malaria as the=
 most prevalent tropical disease in the world: 200 million infected, with 20=
 million made seriously sick by those infections, and 20,000 dead each year=
 because of "schisto," according to World Health Organization (WHO)=
 estimates. Clearly, in the right place, time, and hands, praziquantel could=
 accomplish a lot of public health good.

And it has---to a point. Bayer A.G., the giant German pharmaceutical firm of=
 aspirin-making fame, and E. Merck (now Merck KGaA), one of the oldest=
 operating drug-chemical companies worldwide, discovered praziquantel's=
 antiworm properties over 25 years ago as part of routine screening of new=
 compounds for veterinary purposes. By 1985 approximately one million people=
 had been treated with praziquantel [pronounced pra-ZEE-quan-tel]---an=
 impressive number, but just a start considering the millions more who might=
 benefit from the powerful new medicine. Professor Michael Reich, Taro=
 Takemi Professor of International Health Policy and chair of the School's=
 Department of Population and International Health, directed a research team=
 that published a report from WHO last year on praziquantel. The report put=
 the available supply of the drug in 1993 at about 89 million tablets, which=
 represented only about one-fifth of the WHO estimate of the global need of=
 424 million that year. Even if WHO's calculation of need is high, as some=
 have suggested, that's a huge gap. So the key question in the praziquantel=
 case, says Reich, is "Why is this great drug not available for poor people=
 in poor countries?"

At some level, that question isn't hard to answer. Great drugs are not=
 available because poor countries can't afford to buy them. The team's=
 report estimated that if Nigeria, a country with a very severe=
 schistosomiasis problem, were to buy all the praziquantel it needs, the=
 purchase would eat up almost 18 percent of the ministry of health's budget=
 for drugs and medical equipment---and that's after a steep,=
 UNICEF-negotiated price discount.=20

In the past, some pharmaceutical companies have sought to span the great=
 drug--poor country gap by giving away small quantities of drugs, or by=
 charging less for them in some circumstances, which is what Bayer did with=
 praziquantel. The praziquantel case, however, highlights the limits of=
 Bayer's strategy in expanding access to drugs in developing regions.

Merck marks the way=20

In the late 1980s, another pharmaceutical company took a dramatically=
 different approach to the same problem of getting good drugs to poor=
 people. In October 1987, Merck & Co., Inc. in Whitehouse Station, N.J.,=
 announced it would donate, rather than sell, the human formulation of its=
 big-selling veterinary antiworm medicine, ivermectin, "for as long as it=
 might be needed" to as many people necessary to combat onchocerciasis, or=
 river blindness. In the past 12 years, the Mectizan (the brand name for=
 ivermectin) Donation Program has enabled more than 100 million treatments=
 of onchocerciasis and, in 1998, nearly 25 million people---typically very=
 poor---had been treated in 31 countries in Africa and Latin America and in=
 Yemen in the Middle East.

In the late 1990s, the Merck program is generally considered a public health=
 success, and the program has been emulated by a number of other drug=
 companies. In 1996 the British drug company Glaxo Wellcome, perhaps best=
 known as the maker of AZT, the AIDS drug, started a "controlled donation=
 program" of its antimalaria drug, Malarone. Two years later, SmithKline=
 Beecham, another British drug company, launched its albendazole program,=
 which is perhaps most ambitious yet: the 20-year goal of this collaboration=
 with WHO is the elimination of lymphatic filariasis, a parasitic disease=
 that can lead to disfiguring elephantiasis and serious male genital damage.=
 Then in November 1998, New York--based Pfizer Inc. announced it would=
 donate its best-selling antibiotic, Zithromax, as part of a large,=
 integrated, five-country effort to control trachoma, which like=
 onchocerciasis, is a disease that can lead to blindness and typically=
 affects the poor in developing countries.

The Pfizer program has close ties to the School. Pfizer and the Edna=
 McConnell Clark Foundation in New York have formed the International=
 Trachoma Initiative to run the azithromycin (the generic name for=
 Zithromax) program. Joseph Cook, MPH'68, a longtime Clark Foundation=
 official, is executive director, and Jeff Mecaskey, SM'90, is program=
 director. Adetokunbo Lucas, SM'64, adjunct professor of population and=
 international health and one of this year's Alumni Award of Merit winners=
 (see page 58), serves on the initiative's expert committee as does Reich.=
 The Clark Foundation also commissioned Reich to write a report that served=
 as background for the trachoma initiative. "It was part of a facilitation=
 effort to bring together a private foundation and a private corporation,=
 which had different styles and organizational cultures," says Reich.

Why now?

The drug donation programs have become popular for several reasons. These=
 are good times in the drug industry, and healthy bottom lines do make it=
 easier for corporations to be generous. Pfizer, for example, announced a=
 three-for-one stock split in April 1999 as sales of Viagra and a new=
 arthritis drug, Celebrex (comarketed with G.D. Searle), have skyrocketed.=
 Merck and the other donating companies are also reporting quarter after=
 quarter of revenue and profit increases.

Several of the drugs are significantly better than prior therapies---more=
 effective, safer, and easier to administer. People can fight off=
 onchocerciasis-induced blindness by taking a single, annual dose of=
 ivermectin. Research in the early 1980s showed that the previous therapy=
 for the disease, a drug called diethyl-carbamazine citrate (DEC), caused=
 severe damage to the eye and increased the risk of blindness. Ivermectin=
 safely kills the microfilariae of the disease-causing Onchocerca volvulus=
 worm; the drug developed to kill the adult worms, suramin sodium, turned=
 out to have toxic side effects and could only be given intravenously at=
 weekly intervals. Trachoma can be treated with another antibiotic,=
 tetracycline. But it comes in ointment form and must be applied to the eyes=
 twice a day for about six weeks to be effective. Like ivermectin, Pfizer's=
 azithromycin is a one-dose, once-a-year proposition. SmithKline Beecham=
 says the goal of eliminating lymphatic filariasis is realistic because the=
 traditional antifilarial treatments of ivermectin and DEC are highly=
 effective in breaking disease transmission when co-administered with=
 albendazole, the antiparasitic drug it is donating. The company also cites=
 rapid, easy-to-use, and less expensive screening tests for the disease.=
 Glaxo Wellcome's Malarone isn't easier to administer than other antimalaria=
 therapies because it must be given over a three-day period, but the drug=
 can be a lifesaver for people infected with a strain of the disease=
 resistant to standard remedies, such as chloroquine and fansidar.

As celebrated as Merck's Mectizan program is now, executives at other drug=
 companies were initially opposed to it, according to Power and=
 Responsibility, a 1997 book written by Lee A. Tavis, a University of Notre=
 Dame business professor. Reich says Merck officials were originally=
 concerned that giving ivermectin away for free would set a bad example: "I=
 think the record shows that instead of it being a bad precedent, it has=
 been seen as a pathbreaking precedent---that other companies have looked at=
 the Merck ivermectin experience and see the way it has enhanced corporate=
 values and corporate image in ways that Merck had not originally=
 anticipated. It has become in some sense a touchstone for Merck." To=
 illustrate the point, Reich notes that Merck has a sculpture of a child=
 leading a blind man (a common scene in areas afflicted by onchocerciasis=
 and other blindness-inducing diseases) prominently on display at its=
 corporate headquarters. The World Bank---which has agreed to raise funds to=
 finance onchocerciasis control efforts, including distribution of the drug,=
 to the tune of about $132 million over an 8 to 12 year period---has a=
 replica of the same statue in its new headquarters in Washington. The=
 statue also stands at The Carter Center in Atlanta, reflecting that=
 organization's commitment to the river blindness cause, and this fall a=
 fourth will be installed at WH0 headquarters in Geneva, to represent the=
 role it has played in this partnership.

Questioning motives

These drug donation programs do not come without problems and controversy.=
 Richard Laing, a professor of international health at the Boston University=
 School of Public Health, says the ivermectin program is on balance a=
 positive effort that is meeting a real need. "But it is not easy to=
 administer," he continues, "and these are incredibly poor countries so=
 there are always opportunity costs." Money spent on ivermectin distribution=
 and onchocerciasis control might go, argues Laing, to other programs like=
 meningitis and yellow fever control,=20both of which have suffered badly=
 from the collapse of vaccine programs. Besides, Laing says the generosity=
 of the drug donation programs needs to be put in some perspective. In=
 exchange for good publicity and a tax write-off if the drugs are donated to=
 a charitable organization, he notes, all a company needs to do is make a=
 little more of what is often a very popular, and profitable, drug---and=
 frequently in drug manufacturing, the actual production costs of making a=
 drug are quite low.

Philippa Saunders, at the Essential Drugs Project in London, a non-profit=
 group that supports NGO pharmaceutical services in developing countries, is=
 generally supportive of drug company donation programs and says that the=
 ivermectin program has "proven itself" over the past 11 years. Saunders=
 notes, however, that every donation scheme is unique and must be assessed=
 for its potential problems as well as benefits: "There are clearly much=
 greater challenges in administering combinations of drugs, as is proposed=
 for lymphatic filariasis, than single ones," she says. Saunders also=
 comments that the misgivings of some NGOs and consumer groups may be=
 justified as other drugs of great potential public health value are coming=
 on the market at prices higher than poor countries can afford. "There is a=
 suspicion," she says, "that the donation schemes of individual companies=
 are, in reality, public relations exercises designed to undermine the case=
 for fair trade in drugs."

On the other hand, these donation programs meet important public health=
 goals that most likely wouldn't have been achieved in any other way, argue=
 Tavis and Reich. "The victims of onchocerciasis were in desperate physical=
 as well as economic need," wrote Tavis. "Their only assistance was through=
 the WHO spraying program, a preventive but not curative alternative. Merck=
 was in a very real sense their last resort, as the only institution in the=
 world, public or private, with a potential cure." Tavis adds that even=
 though Merck was not in proximity to the disease sufferers, the company=
 created the "capability of making a difference." Reich notes that Merck=
 might have tried to exploit its monopoly position as having the only=
 effective drug against onchocerciasis. "Instead," he says, "Merck made the=
 decision to donate ivermectin, which has spared millions of people from=
 blindness."

Building partnerships

Brian Bagnall, the U.S.-based project director for SmithKline Beecham, quips=
 that "it is much harder to give a drug away than it is to sell it." The=
 donation is just the first step, after all, and a fraction of the total=
 cost of a drug donation program once distribution and the training of=
 health workers are factored in. Moreover, pick almost any disease anywhere,=
 and there is a tangle of existing, and sometimes competing, interests with=
 which to deal, ranging from ministries of health to WHO to NGOs to local=
 hospitals and health clinics. "One of the key lessons of the successful=
 donation program is to get very different organizations to work together=
 across a complicated distribution chain," comments Reich. "It is bringing=
 together private companies, private foundations, nongovernmental=
 organizations, governmental organizations, health facilities, and=
 patients---people---and making sure that everyone has a reasonably good=
 understanding of what the others are doing and what their own particular=
 roles and responsibilities are." But while this cooperative, joint--problem=
 solving approach may be complicated, it may also be just the thing that=
 makes a donation program work. Says Bagnall, "The reality is that we are=
 all finding it essential to be highly involved in the entire program and to=
 help coalitions of partners solve unique and complex problems through=
 clinical research, community attention, training, distribution logistics,=
 political will, funding, and more." He notes that his company regards the=
 albendazole program as a chain of partnerships: "Neither SmithKline Beecham=
 nor WHO can do this alone. It's all about coalition building."

Working with WHO

Each of the drug donation programs has followed a different path in working=
 with WHO. Merck's relationship with WHO goes back to the late 1970s when a=
 Merck scientist participated in a working group of WHO's Special Program=
 for Research and Training on Tropical Diseases, which gave high priority to=
 the search for a new drug against onchocerciasis. Researchers identified=
 ivermectin in the process of screening drug compounds for anti-onchocercal=
 activity. This result contributed to Merck's critical decision to pursue=
 development of ivermectin for human use. Ivermectin attacks the worm's=
 microfilariae; according to Tavis, WHO onchocerciasis experts had favored=
 drugs that kill adult worms. WHO and Merck cooperated in running the=
 clinical trials that showed that ivermectin was highly efficacious and had=
 limited side effects. But according to Tavis, from 1985 to 1987, when Merck=
 was searching for a donor to buy the drug (unsuccessfully, as it turned=
 out, and thus the decision to give it away), the relationship between the=
 two organizations was tense. Tavis writes that WHO pushed Merck on pricing=
 the drug, and Merck thought WHO should be working harder on promoting its=
 distribution.

Merck decided to establish the donation program in collaboration with the=
 Task Force for Child Survival and Development in Atlanta. The company also=
 set up the Mectizan Expert Committee as an independent entity to review and=
 approve applications from NGOs, ministries of health, and other parties=
 that wanted a role in distributing the drug. WHO representatives have=
 participated in this committee, which is chaired by William Foege, MPH'65,=
 the charismatic former director of the Centers for Disease Control and=
 Prevention, and a global leader in public health. Merck pays for production=
 of the drug and shipping it overseas; once the shipment reaches the=
 consignee, the NGO is in charge of getting the drug to people who need it.

One of the larger participating NGOs in the ivermectin program is The Carter=
 Center, which in 1996 incorporated the operations of the River Blindness=
 Foundation as a major component of its public health programs. Frank=
 Richards is technical director of the Center's Global 2000 River Blindness=
 Program under the leadership of Associate Executive Director Donald=
 Hopkins, MPH'70. In Richards's opinion, well-intentioned health projects=
 have foundered in the past as money and resources were squandered: "People=
 find all sorts of ways to say it in newspeak, but money was given, and it=
 just disappeared down a black hole." He says the ivermectin program, with=
 its independent expert committee, NGO involvement at ground level, and open=
 process of review, is a healthy rejoinder to that waste: "The key word is=
 transparency---transparency and accountability are very real strengths of=
 this program." Brenda Colatrella, the Merck executive who manages the=
 company's ivermectin program, admires the NGOs: "They have shown an amazing=
 effort in the most difficult situations."

In trachoma, the Clark Foundation has worked closely with WHO for the past=
 ten years on several projects and continues to do so. The foundation funded=
 the work that resulted in a simplified grading scheme for the disease as=
 well as three WHO trachoma technical manuals. Pfizer and the Clark=
 Foundation are also major financial supporters of the WHO Alliance on=
 Global Elimination of Trachoma by 2020. In the early 1990s, the Clark=
 Foundation contacted Pfizer about Zithromax. The foundation, along with the=
 company and the National Institute of Allergy and Infectious Disease,=
 supported a three-country trial of the drug that helped lay the scientific=
 foundation for the trachoma initiative. WHO officials are members of the=
 trachoma initiative's expert committee. The five countries targeted by the=
 trachoma initiative were selected from the 16 that WHO's antitrachoma=
 effort has given the highest priority.

SmithKline Beecham has directly engaged WHO in a public-private=
 collaboration. The British company established a joint WHO/SmithKline=
 Beecham committee to plan the albendazole program, including the=
 establishment of the Lymphatic Filariasis Elimination Program Review=
 Committee to oversee applications from NGOs and health ministries. Bagnall,=
 the SmithKline Beecham spokesman, says WHO now sees the "absolute necessity=
 of working with the private sector" under the new leadership of Gro Harlem=
 Brundtland, MPH'65: "You have to distinguish between the new WHO and the=
 old WHO. You have to be careful about labeling WHO with stereotype=
 opinions."

More ambitious programs

For now, Merck's ivermectin program has the most solid track record with=
 just over a decade of experience. The International Trachoma Initiative is=
 just getting into gear, approving the national plans for Tanzania and=
 Morocco, with Mali and Vietnam to follow in the fall. The lymphatic=
 filariasis program is just getting started too, but Bagnall says "many=
 people tell us we are moving faster than they could imagine." Still, this=
 program, which depends on the co-administration of SmithKline Beecham's=
 albendazole with either ivermectin or DEC, is only at the point of=
 reviewing national disease elimination plans.

These other programs are also tackling bigger health problems.=
 Onchocerciasis is a major cause of blindness in the world. WHO estimates=
 that 100 million people are at risk of getting the disease, 17=D018 million=
 have it, and 270,000 have been blinded by it. Yet compare those numbers to=
 trachoma: 540 million (about one out of every ten people in the world) at=
 risk and six million blinded. Lymphatic filariasis is a health threat for=
 900 million (one out of every six people in the world) and affects 120=
 million. Some have questioned whether SmithKline Beecham, in particular,=
 has bitten off more than it can chew. But David Addiss, a medical=
 epidemiologist at the CDC and an expert on lymphatic filariasis, says the=
 technical tools are there for stamping out the disease. And he credits the=
 SmithKline Beecham donation with "energizing the whole field" of lymphatic=
 filariasis research and efforts to eliminate it as a major health problem.=
 Pfizer and the Clark Foundation have taken a more cautious route, limiting=
 their trachoma initiative to five countries for two years, and longer if=
 the program is successful.

With the rise in donation programs, there is some apprehension among both=
 drug companies and NGOs that the programs will start competing with each=
 other and stretch the NGOs that do the ground-level work too thin.=
 Colatrella says the drug companies proactively established the Donor=
 Coordination Group to address these concerns. By July, she says they plan=
 to spell out some common objectives.

But in Laing's opinion these donation programs are a "magic bullet" approach=
 to public health that wins headlines but ends up taking away from a=
 community development approach that emphasizes sanitation, among other=
 things. In public health circles, this argument would be familiar: it is=
 the well-known vertical v. horizontal health program debate. "Azithromycin=
 for trachoma is not necessary in the U.S. because people have clean water,"=
 says Laing. "Providing azithromycin is a Band-Aid on the underlying=
 problem." But Reich says "the problem is that when you get to marginalized,=
 disadvantaged populations on the periphery of poor societies, the existing=
 horizontal health services don't tend to be particularly good. These=
 donation programs have the potential to provide lasting benefits for=
 people." Moreover, he continues, for onchocerciasis, local hygienic=
 measures cannot protect the population at risk because of the habits of the=
 flies that spread the disease. Reich says it is doubtful that general=
 development would cause the disease to disappear without spraying the=
 breeding sites of the flies or treating infected people. And as for=
 trachoma, supplies of clean water might reduce the risk of future=
 infections, says Reich, but they wouldn't help people who are currently=
 infected. Most often those people are women and children, who also have the=
 highest risk of going blind from an untreated trachoma infection.

Many also believe that the vertical/horizontal choice is a false dichotomy=
 and that so-called vertical programs wind up strengthening and even seeding=
 broader health services at the local level. Cook says in those areas where=
 poverty and poor sanitation exist, an anti-infective agent can be used to=
 reduce transmission of disease but may also actually change human behavior=
 and get to the underlying causes of the disease's continued spread. "This=
 is not simply an antibiotics program," he says and goes on to explain that=
 the trachoma initiative promotes implementation of the WHO-endorsed safe=
 program against trachoma (the S stands for surgery that rotates eyelashes=
 away from cornea, which prevents blindness; the A for antibiotic treatment;=
 the F for face washing; and the E for environmental change). Virginia=
 Turner, MPH'80, a field researcher and eye disease expert working for Helen=
 Keller International in Tanzania, says she fought tooth and nail to make=
 sure that the surgery was first in the formulation for an effective=
 strategy against trachoma because it is the best, most immediate way to=
 prevent blindness. She applauds the Pfizer donation for energizing people=
 working on eye disease in the developing world, but is concerned that the=
 antibiotic part of the safe program could overwhelm the other components.=
 "I am," says Turner, "going to be watching the direction of the program=
 carefully."

Hope for more=20

In the report on praziquantel and schistosomiasis, Reich and his colleagues=
 wrote: "For tropical disease products, companies confront a basic dilemma:=
 the ultimate consumers are usually very poor people in the world's poorest=
 countries." As difficult as the organizational issues and logistics might=
 be, these disease-specific drug donation programs are perhaps one way out=
 of that dilemma, at least for a few select diseases. Tavis says the=
 programs reflect the changing, and more powerful, role of the multinational=
 corporation in world affairs. "The nation-state no longer plays the role it=
 did," he said during a recent interview. "The multinational corporation is=
 playing a greater role and with this added power comes responsibility.=
 Their own employees are demanding it."

Reich is hopeful. He hopes there will be more, not fewer, drug donation=
 programs: "I think other companies are beginning to see that this is=
 something they should do to improve the welfare of poor people in poor=
 countries and to enhance corporate morale and image."

--------------------------------
Philippa Saunders & Gill Stoker
Essential Drugs Project
77 Lee Road
Blackheath
London SE3 9EN
UK

tel/fax   44 (0)20 8318 1419
email     edp@gn.apc.org
 
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