E-DRUG: Donated Drugs for Public Health
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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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