It's Not Our Fault, Says Drug Industry...Again


Applied Clinical Trials

Applied Clinical TrialsApplied Clinical Trials-12-01-2004

Pharma's finger of blame once again points outward, never inward.

Pharma's finger of blame once again points outward, never inward.

Lack of clinical trials infrastructure "may become an important bottleneck" for provision of medicines in poorer countries, warns a new pharmaceutical industry attempt to justify and defend the lack of effective action to date on medicines provision for diseases in the developing world.

A just-published study from the International Federation of Pharmaceutical Manufacturers Associations (IFPMA) called "Research and Development for Neglected Diseases: Lessons Learned and Remaining Challenges" [available at] aims to deflect some of the criticism the drug industry has been attracting as the north-south gap in medicines provision widens.

The study is guardedly optimistic about the future: "The number of compounds in development for these diseases will increase," it claims. But one of the key gaps in delivery is likely to be an appropriate clinical trial framework.

"Neglected diseases may represent a particular challenge in terms of clinical trials, as they affect the most marginalized populations, without access to any (even most basic) healthcare facilities," says the industry publication. In a bid to focus attention on failings elsewhere than among multinational drug firms, it argues that populations often have poor literacy, creating additional difficulties for overcoming culture barriers and ensuring genuine informed consent. In addition, it points out, military conflicts in regions where neglected diseases are endemic "may have a negative impact on the discipline required to conduct valid trials."

"In short, clinical trials infrastructure in developing countries where neglected diseases are endemic seems very limited," the study concludes. And as a consequence, different R&D projects within a new scheme for anti-malarials may soon be competing with each other not for financial resources, but for clinical trials sites in Africa, it says.In addition, IFPMA highlights the "important issue of regulatory capacities in developing countries that are needed to fully evaluate regulatory submissions." Currently, most developing countries' regulatory authorities rely on one or more developed country approval. This is an imperfect situation, IFPMA points out, since authorities such as the Food and Drug Administration or the European Medicines Evaluation Agency are obliged to apply northern risk-benefit calculations to their evaluations, and these may be inappropriate in the target countries.

For instance, the rotavirus vaccine was withdrawn from the U.S. market in 1999, due to the observed risk of developing intus susception during the postmarketing surveillance. This risk, while significant by U.S. standards (where very few deaths result from diarrhea), could probably be accepted in high-burden developing countries where 1.8 million children die of diarrhea every year, says IFPMA.

IFPMA doesn't offer the solutions itself, but it does offer pointers to some possible solutions. It urges "capacity building initiatives" targeting clinical trials. It says "different stakeholders need to collaborate to develop necessary infrastructure, including appropriate training of clinicians."

As it points out, some of this is already contemplated in the newly established European & Developing Countries Clinical Trials Partnership (about which this column has provided updates over the last year or so), with a focus on capacity building for HIV/AIDS, malaria, and tuberculosis trials. But as it also points out, this partnership "needs to establish effective working relationships with existing R&D organizations and also needs to be sufficiently funded to succeed. Without any doubt, an expanded initiative is needed for neglected diseases."

IFPMA insists that urgent and major efforts are required so developing countries can conduct late-stage clinical trials, have swift product registration and postapproval evaluation of medicines, and identify the best ways of applying new medicines to neglected diseases. And to deal with the authorization dilemma, "concerted action between regulatory authorities and drug companies is needed to develop innovative models for drug assessment and thus increase R&D productivity."

Genuine difficulties
There is no doubt that the drug industry is not the only culprit-and maybe not even the chief culprit-in the continuing absence of effective treatments for disease in many poor countries. While a large number of the world's poorest people continue to bear a heavy but avoidable health burden, there are many other factors at play besides the availability of medicines.

The IFPMA study particularly highlights poverty and political instability, and spells out how even the best-intentioned approaches are often frustrated by on-the-ground circumstances. It alludes to "often questionable government prioritization" in disease-ridden countries.

And it makes clear that for many diseases, the remedies already exist but are just not being deployed. "Most of [the] diseases that disproportionately affect low-income countries can be treated or prevented with easily available existing agents, such as medicines from the WHO's Essential Drugs List," it observes drily.

Genuine achievements
The study speaks glowingly of the "vast array of on-going efforts to develop and deliver new medicines" for populations in poor countries, and details many of the genuine achievements to date. It evokes "the sustained commitment" of pharmaceutical companies, "contributing significant resources and expertise and making significant new investments that focus exclusively on the health problems of poor populations."

Disingenuous disclaimers
But the industry, in its determination to paint itself in decent colors, runs the risk of provoking yet more obloquy if it is too insistent on its innocence.

It piously-almost smugly-remarks that "important health needs of poor populations are neglected despite the availability of safe, effective, and inexpensive medical tools that if applied properly, could rid these populations of their excessive health burden." And where treatments are not available, it blames "the lack of interest among public health policy makers to invest in neglected diseases control," and the neglect of crucial new knowledge by the scientific community.

The study displays a determination to talk tough that may win it fewer friends than it needs in this debate. An underlying message that is uncomfortably close to "don't blame us, we need to make profits" repeats itself throughout the study. It insists that any discussion of "the need for novel interventions" should be carefully framed so that it does not "lead to unnecessary resource waste and create expectations that cannot be met." And in a tone redolent of a financial manager rather than a philanthropist, it urges: "Concerted efforts need to be made to streamline the development of new drugs in order to reduce the overall cost of R&D for neglected diseases."

New starts for EU regulation
Meanwhile, back home, it is all-change time, with a new European Commission taking over in Brussels (see the regulatory agencies update in this issue). New rules are in place for the new European drug assessment body, the Committee for Medicinal Products for Human Use (CMPH), which has replaced the former Committee for Proprietary Medicinal Products within the European Medicines Agency in London. The new committee has just published its rules of procedure-which in summary amount to the following.

It will consist of one member appointed by each of the EU Member States for a renewable term of three years, and up to five co-opted expert members. For each scientific evaluation of a medicine, a rapporteur will be appointed from among the members of the Committee "on the basis of objective criteria," who will head an assessment team selected from among the pool of designated EU experts. But the committee itself will adopt the opinion on each particular issue.

The committee will also establish working parties and scientific advisory groups. And it may seek the services of experts in specific scientific or technical fields, particularly on clinical safety issues.

Applicants can ask to be allowed to provide oral explanations in connection with an evaluation procedure, and the committee can ask any other relevant third party for a hearing too.

For opinions where a re-examination is necessary-usually following an appeal from a company-a different rapporteur will be appointed, with "best endeavours to ensure a new examination, independent from the first opinion."

Advice will be given to applicants for marketing authorizations on the tests and trials necessary to demonstrate the quality, safety, and efficacy of their products, particularly for the development of new therapies.

The quorum required for adoption of scientific opinions or recommendations is set at two thirds of the members. "Whenever possible," adoption is to be by consensus; if not by consensus, then by absolute majority. Divergent positions-and the names of those expressing them-are to be mentioned in the opinion.

Provision is made for urgent decisions on pharmacovigilance, serious concerns on public health, or quality defects.

No members or experts may have direct interests in the pharmaceutical industry which could affect their impartiality, and they must undertake to act in the public interest and in an independent manner, and make an annual declaration of their financial interests.

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