Ethics & Pandemics

The Beginning of a Solution?

The news from Jarkarta, according to Reuters and the WHO, seems to be that Indonesia has agreed to resume sending avian flu isolates to the WHO.  According to Minister of Health Siti Fadillah Supari, this will begin "immediately." 

A report in the Wall Street Journal (subscription required), however, adds what seems to be a pretty important qualification:

The compromise, announced at the end of a two-day meeting organized by the WHO in Jakarta, means scientists around the world will be able to study the freshest and potentially most important strains of the avian-influenza virus. However, that access won't be extended to drug companies such as Sanofi-Aventis SA of France and GlaxoSmithKline PLC of Britain, both of which manufacture bird-flu vaccines and need access to new strains of the disease to make sure their products are up-to-date and effective.

This, in short, means the debate is far from over.  As part of the agreement, the WHO will be revising the Terms of Reference for WHO laboratories.  My fingers are crossed, but it seems to me like there's still a lot that could go wrong here.  Lest we think the problem is entirely behind us, MoH Supari remarked, "We trust WHO will not violate our trust, because this is related to the WHO's credibility."  In other words, they've offered to take the first step to break the stalemate in exchange for a pledge from WHO that the status quo will indeed change.  But this first step is clearly a conditional one. 

Some have advanced the entirely foreseeable and quite disastrous long-term consequences of not sharing samples as proof that Indonesia should never have done what it did.  I would disagree--up to a point.  Sadly, barely anyone would have paid attention if Indonesia had simply registered it's complaint without threatening any real consequences. 

While Indonesia has a made a clear case for why the status quo for sharing virus samples is inadequate in the short term, it's also becoming clear (if it wasn't already) that no one's interests--not even Indonesia's--are advanced in the long term if different manufacturers don't have access to new samples. It's impossible for me to envision a solution that would not somehow involve for-profit companies having access to viral isolates.  This makes me wonder how far the current agreement can really go.

It's true that Indonesia is collaborating with one company (Baxter) but their candidate vaccine is a 'whole-cell' vaccine, quite different from those being developed by Sanofi, GSK, and other companies.  Clearly it's prudent to move forward with studies of as many different candidate vaccines, adjuvants, and production technologies as possible (and hence, to supply seed viruses to as many manufacturers as possible). 

I see two reasons for this.  This first relates to global supply: More manufacturers means more vaccine available globally, which I think all can agree is a good thing.  The second relates to safety and efficacy of the vaccines: What if it turned out that Company X's vaccine was unsafe or ineffective (or just less safe or less effective than Company Y's)?  Note: I'm not saying this is the case with Baxter's vaccine.  I'm just saying that bad things can happen, even to good vaccines, as with Chiron's seasonal flu vaccine in 2004. 

 

Global Equity and Intellectual Property

As usual, Indonesia is foremost on my mind these days.  From the Intellectual Property Watch blog, this post by Tove Iren S. Gerhardsen provides an interesting analysis of the current impasse on virus sharing.  Apparently, Indonesia may have a sovereign right to viruses circulating in the country, since the Convention on Biological Diversity (to which Indonesia is a party) protects countries' ownership of genetic material.  They may have a sovereign right to it -- this hasn't exactly been tested.  I've heard someone at the World Bank suggest the same thing.  I'm no expert on intellectual property, so I'll let the IP-Watch post speak for itself:

Indonesian Avian Flu Stance Reveals Potential Weakness in Global System

The Indonesian government’s reluctance to share avian influenza virus samples to help develop a global vaccine for humans has revealed a weakness in the international flu research system related to developing countries’ concern with the impact of intellectual property rights on public health.

Developing countries are concerned that if they supply avian influenza virus samples for free to the international health community under the World Health Organization (WHO) system, the samples will be used to develop patented vaccines targeted to wealthy countries and too expensive for developing countries to purchase. The market for traditional influenza vaccines has been in industrialised countries, so it has been a “north-north process,” a WHO official told Intellectual Property Watch. 

“We are very worried,” an Indonesian official told Intellectual Property Watch, adding that there is an “unfair mechanism” regarding the sharing of samples of viruses. Some manufacturers will use the samples to develop vaccines, but there is no guarantee that poor developing countries such as Indonesia would be provided with the vaccine, as manufacturers’ production capacity is only 40 million, he said, referring to the more than 6 billion people in the world. There is a “high gap in demand and supply,” he said.

Indonesia is the hardest-hit country in terms of human deaths from avian influenza, according to the WHO, which said there has been a total of 277 cases of avian flu in human beings worldwide.

The sharing of virus strains links into another current IP policy issue. The virus samples taken from people affected by H5N1, the most common avian flu virus, also may be considered genetic material to which, according to the Convention on Biological Diversity (CBD), countries have a sovereign right. If others want to use the genetic material to develop a medicine, for example, they would have to ask permission, disclose the source of the material, and share the possible benefit of the outcome with the owners of the genetic material.

But as the CBD is soft law and not legally binding, a number of developing countries are pushing to amend the legally binding World Trade Organization (WTO) Agreement on Trade-Related Aspects of Intellectual Property Rights (TRIPS) to include this requirement in patent applications. The relationship between the CBD and TRIPS is one of the most important issues for developing countries in the current round of trade liberalisation negotiations at the WTO, referred to as the Doha Round.

continue reading this post at Intellectual Property Watch....

Viral samples, continued

This is the story that never dies--nor, I suppose, should it. 

After some apparent progress last month, it seems like things are back to square one (or close to it).  The agreement reached between the Government of Indonesia and the WHO about resuming the sharing of viral samples seems to have been an agreement more in principle than in actuality (at least so far).  Soon after the agreement was announced, there were suggestions from both sides to the effect of "that's not quite what we agreed to."  This Canadian Press article by Helen Branswell sums it up nicely.  It's dated March 1st, but it's the most complete account I've seen to date:

[Indonesian MoH] Supari said she had received verbal assurances from WHO director general Dr. Margaret Chan that the viruses would be used only to study the evolution of H5N1 and not for production of vaccine. Once those assurances have been put in writing, she said, Indonesia will again ship H5N1 viruses with international laboratories.

A spokesperson for the agency, Dick Thompson, told the Associated Press that Supari's suggestion she'd been given a guarantee that the viruses would not be shared for vaccine development was incorrect. Thompson later said that a letter to Indonesia from the WHO was still being drafted and he had been wrong to imply anything about its contents.

The WHO's influenza czar, Dr. David Heymann, refused to disclose what Chan had told Supari.

"The communications between WHO and ministers are confidential. We can't give any information out about them," Heymann said from Geneva.

It seems unlikely, however, that the international health body could agree to permanently place a limit on how viruses from Indonesia could be used. Doing so would violate a resolution approved by the agency's executive board in January.

[Update: Here's a 3/14 update from CIDRAP that says essentially the same thing.]

It all seems to hinge around an as yet unwritten "Material Transfer Agreement."  So far as I understand it, Indonesia's primary criterion for approving the MTA seems to be that no viral samples that leave Indonesia will be used for commercial purposes.  They could be used for research (genetic analysis, possibly for vaccine research, etc.) or for producing a vaccine from which no profit is derived, but probably not for anything else. 

From the WHO's point of view, it's doesn't seem like such an agreement would be agreeable.  In fact, it looks like WHO might not even be authorized to reach such an agreement if they wanted to.  So the impasse seems not to have gone away.  That said, I expect that diplomatic efforts, shielded from the media, are ongoing.  A regional meeting of Asia-Pacific health ministers and others (I don't know who the "others" are) on March 27-28 may point to a way forward. Call me hopeful.

I'm just speculating here, but I wonder what the ultimate impact would be if Indonesia didn't resume sharing viral samples.  Crofsblogs' H5N1 blog (which I cannot praise enough) has an insightful post and reader comments about the same subject here. 

My personal take is that, with global trade and travel being what they are, if a pandemic were to begin in Indonesia, it would only be a matter of weeks (or perhaps even days) before a pandemic-capable virus crossed the border into a 'virus-sharing' country (Malaysia, Singapore, the Philppines, Australia).  This is not to say that failure to share samples won't have any effect.  Clearly it will limit research in the interim, e.g., preventing us from understanding how the virus is mutating.  But it's not clear how long it would delay production of an actual pandemic vaccine. 

The other question lingering in my mind--again, purely speculative--is whether NGOs (Red Cross/Crescent, Doctors Without Borders, and the like) will have any role here.  Presumably, they're not bound by the same rules that the Indonesian government claims it is bound by.  They cannot afford to flout the government or its policies, but since their mission is truly global in scope, might they see value in discreetly transporting samples out of the country?  And would the WHO be willing to receive samples provided by NGOs instead of governments? 

I don't mean to suggest that Indonesia's position is something that just needs to be circumvented.  I think it poses important questions of global health equity that we cannot afford to ignore.  Nor are these questions specific to influenza.  A not wholly unrelated debate is raging about governments' rights to issue compulsory licenses for essential medicines like antiretrovirals for HIV.  In fact, I'm worried that if we find 'work-arounds' that allow us to resume business as usual, the important issues will remain unresolved. 

Lecture: Ethical Issues

Prof. Alexander Capron (a Bellagio Group member) delivered the 2007 Johnson & Johnson Health Care lecture at the University of South Carolina School of Law, entitled Ethical Challenges in Preparing for a Pandemic (has links to audio & video).  Prof. Capron, now at USC, was the WHO's first Director of Ethics, Trade, Human Right, & Health Law.  He structures the talk around the broad theme of individual versus group interests.  I'd highly recommend listening to the entire thing (it even made FluWiki's "Tip of the Week"), but here are some of the points I found particularly salient:

He pointed out how ethical considerations are often "buried" within other planning activities.  For example, national pandemic plans that set a goal of "saving the most lives" or minimizing mortality have thereby made an implicit ethical commitment to give preference for treating certain people, i.e., those whose lives are easiest to save by means of whatever interventions are on hand (not the sickest, who will almost certainly die, and not the healthiest, who might likely recover without treatment).  Given the significance of these questions, how can we bring them to the fore?

He described a case study, developed by Harvard ethicist Dan Brock, that highlights the importance of public engagement in prioritization decisions.  The hypothetical case involves four community hospitals that adopt four different policies for allocating antivirals: (A) concentrate on prophylaxis of health care workers; (B) focus on treating patients who are sickest; (C) attempt to maximise survival rates by treating those mose likely to benefit; (D) adopt all 3 strategies, resulting in quicker depletion of drug supplies.  The point of the case study, as I understand it, is to help generate discussion about what sort of allocation strategy to adopt, since these sorts of hard decisions may well be left to local authorities (hospitals, municipalities, etc.).  By outlining different allocation strategies in pretty stark terms, it may be easier for people to voice an opinion about what policy or policies they would recommend.

Regarding international obligations, some very interesting comments about whom we (i.e., donor countries) have obligations toward.  Essentially, our primary responsibility is to help people in developing countries, not to those countries' governments per se.  This seems like a no-brainer, but the implications are quite substantial.  If countries do not have the means or the will to deliver resources (drugs, vaccines, food, water, etc.) efficiently and equitably (by at least some minimal standard), then simply handing over money or supplies to a government might not suffice (and may, in fact, be very unwise).  Think, for example, of Burma (where there were new H5N1 cases reported this week).  This does not mean that obligations to people in such countries would disappear, only that it becomes harder to fulfill those obligations.  Food for thought, with no obvious answers....