E-drug: Gatt and the Gap (2)
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Dear Richard,
The paper you forwarded ('GATT and the Gap: how to save lives', John S.
James, E-Drug 17 Nov. 1998) is quite interesting but appeared
restrictive because referring to the only emerged part of the iceberg.
The essential questions and potential resulting answers concern contents
of pharmaceutical research and development (R&D) and not only prices.
To better understand current situation that developing countries are
facing up (high prices and low accessibility, R&D deficiency for
tropical diseases and lack of pharmacopeia renewal), we can roughly
divide history of pharmaceutical R&D in 3 stages or periods.
1/ 'Historic period'
From 1910 to the 1970s, the pharmaceutical industry's contribution was
crucial to the fight against prevailing diseases in Western countries
(infectious diseases, cardio-vascular diseases... etc. ) as well for
endemic tropical diseases (protozoan parasites infections... etc.). Most
of the available therapeutic tools for the treatment of main tropical
diseases were developed during this part of the century (the
aminoquinoleins and others acridine derivatives for malaria, the
arsenicals in the treatment of sleeping sickness, the antimonials for
leishmaniasis, the vaccines for the expanding programme of
immunisation... etc.).
During this period the future of Southern countries was closely tied
with the one of Western countries, most of these countries were colonial
territories (Sub-saharian Africa, South-east Asia, India... ). Fighting
against tropical diseases with chloroquine, melarsoprol or suramin meant
firstly to preserve health of expatriates or soldiers and in this way to
promote economic development of colonies which were considered as
suppliers of raw materials (ores, cereals, manpower). Tropical diseases
hindered this development. Health and well-being of Southern native
people - the working force - were taking into account from an economic
point of view. For pharmaceutical companies (such as Winthrop , Pfizer,
Specia, Janssen or Bayer Co.) developing and marketing Prontosil TN,
ampicillin or chloroquine met popular demand (e.g., the one of the
British citizen of England or India, the one of the French citizen of
France or Ivory coast) and the one of ministries of colonies.
Most of the available essential drugs were developed in the first part
of this century and are not without risk.
2/ 'King Market period'
From the 1970s context began to change : decolonization came to an end
(puting a stop to strategic significance of the South), economies were
going towards globalization with the triumph of market, demographic
dynamics tended to reverse... nearly all African and South-east Asia
territories were independent, having the difficult responsability to
take charge of their fate and health.
In this landscape, medicine products appeared as common industrial
products as a car or a washing machine, pharmaceutical industry
operating like any private industry and making investment decisions to
maximize future returns from the money invested. Because R&D activities
are a long process (2 to 5 years for screening and discovery phase, 8 to
9 years for clinical testing phase), a costly process (estimated US$
150-200 million per successful product, including cost of failures and
cost of capital, shared between pharmaceutical industry and Academia or
university laboratories) and uncertain, pharmaceutical companies shifted
progressively to more profitable markets (cardio-vascular diseases,
cancer, degenerative diseases... etc.).
Since that time, shareholder value prevails over public health concerns
and the most profitable segments of the market leave progressively
tropical medicine largely out of the equation.
Of the 1223 new chemical entities commercialized worldwide during
1975-1996, 379 were real therapeutic innovations and less than 1% were
destinated for tropical diseases (results in Trouiller, 1998 in press),
of which only a minority may be claimed by Western pharmaceutical
companies as genuine products of their research. The majority were
incidental discoveries recovered from veterinary medicine (e.g.,
albendazole, ivermectin, praziquantel... etc.) or molecules discovered
or rediscovered by governmental or military academic institutions and
only later commercialized by the Western industry (e.g., halofantrine,
mefloquine, artemisinin derivatives). Furthermore many drugs were
endangered if their effectiveness in AIDS-related opportunistic
infections had not been discovered (e.g., atovaquone, pentamidin) and
some have been abandoned despite their usefulness (eg, eflornithine for
the treatment of sleeping sickness) or are likely to be abandonned in
the future (e.g., melarsoprol, nifurtimox... ) because both are
unprofitable.
Anyway, additional drugs became available as 'essential drugs', but only
because discovered, designed and used for Western wealthy markets (e.g.,
ceftazidime, ciprofloxacin, zidovudine, second generation vaccines as
Hib or hepatitis B vaccine) and with a limited use and a low
affordability in developing countries because of pricing levels.
In such a context, the 'essential drug' concept gets all its meaning: we
do preserve as a valuable capital this available pharmacopeia by a
rational use, all the more so since many of germs (bacteria or
parasites) have developed some degree of resistance and most of the
available compounds belong to a restricted group of chemical structures.
3/ 'Period of Uncertainties'
This is the current period. Finally we got the awareness of all these
matters of concern.
3.1 : R&D
R&D is becoming more and more complex, successful drug development
requiring large and dedicated teams of professionals to encompass
discovery and the various steps of development, registration (with
FDA-like standards) and distribution. All these expertise and ressources
are mainly available within the pharmaceutical industry. But this
industry is reluctant to conduct tropical R&D because of (i) its costs
and the absence of investments recovery (unprofitable segments or long
pay-back period), (ii) unfair competition and counterfeit products
(e.g., praziquantel Bayer). Despite indisputable progress in the
identification of chemotherapeutic targets and lead compounds, this drug
development pipeline is drying up and no further candidate for
development (antimalarial, antileishmanial drugs... etc.) are expected
in the short-term.
Anyway when commercial incentives are existing, R&D outcomes succeed
rapidly : before 1987 there were some 2 or 3 antiviral agents, during
the short period 1987-1998, 14 antiretroviral drugs have been registred
and marketed for the HIV/AIDS treatment !
So on, it's not a question of know-how or expertise but of R&D strategy
and direction.
3.2 : Prices
Drug prices are highly influenced by the purchasing-power of Western
countries. When accidentally an interesting discovery for a non 'Western
indication' occures, pharmaceutical companies prefer donation programmes
to dual-pricing for wealthy and indigent customers, strategy that could
jeopardize sales of high-priced compounds marketed also for
non-parasitic indications (e.g., atovaquone, ivermectin) or for
originally 'Western indications' (e.g., antiretroviral agents,
ceftazidime, ceftriaxone). Only one small exception to this postulate
(but a try not converted): the NGO 'MSF, France' negociated in 1997 with
Bayer Co. a dual-price system for ciprofloxacin (patented product,
Ciflox) in designated indications (shigellosis infections) and for
geographical limited uses.
Pharmaceutical companies claim for high prices and are in favour of
worlwide single prices for innovator drugs, arguing that R&D is costly.
This argument is inadmissible because (i) exhibited costs of discovering
and developing a new drug are questionable and are shared between public
and private funds (ii) companies are dependant on a number of very high
volume products (the blockbusters) for the majority of their sales and
profits and (iii) according to economic theory, both demand and
production costs play a role in determining the price of a drug and it
is profitable for the manufacturer to lower the price.
Most of the time, governments and other public institutions don't
dispute prices (e.g., antiretroviral agents), 'forgetting' they have
funded one part of R&D process (see the US OTA studies and the Taxol
example) and they finance a sizeable part of drug purchases
(particularly in Europe through social security systems).
3.3 : International and governmental efforts
In spite of appearences, international and national organizations are
acting (e.g., WHO.TDR Tropical diseases programme, the Wellcome Trust,
the European Union Inco DC programme... etc.) but R&D is largely
underfunded (see the Wellcome Trust Audit of international activity,
1996) and public sector has been unable to provide the optimal
environment for such activities (on the contrary, a system is working
for rare diseases - Orphan drug acts - and could be used as an example
for tropical diseases ; see MSF Foundation Report : 'Are tropical
diseases rare diseases ?', Sept. 1998).
There is clearly room for newer approaches. Increased representation of
disease-endemic countries in the process is needed. What is not
appealing to the Western drug industry may well be suited to
small-medium sized start-up companies, particularly in advanced
developing countries (e.g., co-development of pyronaridine and
artemisinin derivatives with a close collaboration between Asian and
Western institutions and private companies). The public and private
sector should explore the facilitation of interaction, alternative
routes of marketing and distribution (e.g., purchase funds) and
optimizing the regulatory process.
Obviously the present profit-driven system is unable to keep pace with
current and evolving needs. This calls for a broader debate on global
drug development strategies, and prices isssues are only one part of it.
Patrice TROUILLER, PharmD, MB
Health-system pharmacist
- University Hospital of Grenoble, France
tel. 00 476.76.54.97, fax. 33 476 76 51 09
e-mail <pat.trouiller@wanadoo.fr>
- MSF Foundation (Doctors without borders), Paris, France
[thanks Patrice - an important topic. The discussion is open! WB]
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