Thursday, July 31, 2014

No Treatment or Vaccine for Ebola, but a $1000 Pill for Hepatitis C

The Ebola virus epidemic in West Africa continues to grow, and now appears to be the worst known epidemic of that disease to date.  In the US and Western Europe, press reports are now raising concerns that the disease could spread there.  For example, CNN, in an article entitled "Ebola Fears Hits Close to Home," was a section headed "Could Ebola spread to the US?" An ABC article was entitled, "How the US Government Could Evacuate Americans with Ebola."

Reasons for fear of spread are the increased mobility of people made possible by air travel, and the lack of specificity of early symptoms of Ebola, so infectious people may not realize the dangers their travel might pose.  A US citizen with Ebola was on his way back to the US via several connections, and made it as far as Lagos, Nigeria before becoming too ill to travel further (per CNN).  Making the fears worse are the high fatality rate of Ebola, the current epidemic included.  According to Vox, the current outbreak is the Zaire subtype of the virus, with an expected mortality rate of 68%.  Finally, there is no known effective treatment or vaccine for the Ebola virus.

Economics, not Science the Reason for Lack of Medical Options for Ebola

The reason there are no vaccines or treatments available for Ebola does not appear to be the scientific difficulty involved in developing them.  Vox also published a discussion for the economic genesis of the problem:

 Researchers have devoted lots of time to building a vaccine that could stop the disease altogether — and according to Daniel Bausch, a Tulane professor who researches Ebola and other infectious diseases, they're making really significant progress.

Bausch says that the obstacle to developing an Ebola vaccine isn't the science; researchers have actually made really great strides in figuring out how to fight back against Ebola and the Marburg virus, a similar disease.

'We now have a couple of different vaccine platforms that have shown to be protective with non-human primates,' says Bausch, who has received awards for his work containing disease outbreaks in Uganda. He is currently stationed in Lima, Peru, as the director of the emerging infections department of Naval Medical Research Unit 6.

The problem, instead, is the economics of drug development. Pharmaceutical companies have little incentive to pour research and development dollars into curing a disease that surfaces sporadically in low-income, African countries. They aren't likely to see a large pay-off at the end — and could stand to lose money.

Prof Bausch elaborated,

These outbreaks affect the poorest communities on the planet. Although they do create incredible upheaval, they are relatively rare events. So if you look at the interest of pharmaceutical companies, there is not huge enthusiasm to take an Ebola drug through phase one, two, and three of a trial and make an Ebola vaccine that maybe a few tens of thousands or hundreds of thousands of people will use.

Of course, that assumes that this outbreak, like previous ones, will remain relatively confined, at least to Africa.

The 10/90 Gap

So the implication is that had things been otherwise, those in developed countries now worried that Ebola could spread their way could have been reassured by the availability of a vaccine, or other treatment.

The irony, if that is the right word, is that we do not have an effective treatment or vaccine for a viral disease that is relatively easily spread, and could likely rapidly kill nearly 70% of those infected.  Yet in the last months, we have been arguing about how the use of an extremely expensive treatment for another viral disease that is difficult to spread, and may kill a few percent of its victims over up to 20 or 30 years after infection.

I am referring, of course, to Sovaldi, the recently announced $1000 pill for hepatitis C.  Hepatitis C does affect a lot of people, including relatively affluent people in developed countries.  As we noted previously, though, the majority of people infected with hepatitis C will never have serious medical repercussion from it.  Small proportions of patients will eventually develop severe liver disease, including cirrhosis, liver failure, and liver cancer, and may die from the disease.  (See the report by the Center for Evidence Based Policy). Yet the treatment is being promoted for all patients with hepatitis C, most of whom could not benefit from treatment.  Furthermore, the evidence that treatment will actually prevent bad clinical outcomes, cirrhosis, liver failure, liver cancer, and premature death, is weak (look here).   Yet considerable money was devoted to developing multiple hepatitis C treatments, with the expectation that huge amounts of money could be made from selling them.

This is an example of the 10/90 gap

A long time ago, in 1998, I was invited to Forum 2 of an organization called the Global Forum for Health Research  The GFHR was an organization dedicated to overcoming the "10/90 gap":

Less than 10% of the worldwide expenditure on health research and development is devoted to the major health problems of 90% of the population

Yet the 10/90 gap is probably getting worse.  In the US, our health care has now been heavily influenced by advocates of neoliberalism, or economism.  Health care is now largely run by generic managers trained in business schools, with no specific training or expertise in health care, and doubtful loyalty to its values.  Current business school dogma emphasizes the primacy of economic efficiency over all other goals (look here), to maximize "shareholder value," which usually practically means maximizing short term revenue, to the immediate advantage of shareholders sometimes, but nearly always to the great and immediate financial advantage of paid managers and executives.  The emphasis on short term revenue uber alles helps explain how we have multiple expensive hepatitis C drugs, and no Ebola drugs or vaccines.

The real irony is now that some very well paid managers may be worrying about the possibility of contracting Ebola whose transmission was facilitated by our increasingly global economy, globalized in part due to the advocacy of those advocating neoliberalism and economism.


Unfortunately, the fortunes of the Global Forum for Health Research seem to have faded.  It went into sudden decline in 2010, and was subsumed into COHRED, the Council on Health Research for Development.  The last Global Forum meeting was in 2012, although there seem to be plans for another next year.    Meanwhile, multiple international organizations. including Medicins Sans Frontieres, established a Drugs for Neglected Diseases initiative, although its progress seems to be slow (see Pedrique B, Strub-Wourgaft N, Some C et al.  The drug and vaccine landscape for neglected diseases (2000-11): a systematic assessment.  Lancet Glob Health 2013; 1: e371.  Link here.).

In my humble opinion, as long as much of the health care system is run so as to put short-term revenue ahead of all else, a manifestation of financialization encouraged by the generic managers who run so much of health, partly in their own self-interest, and by business schools promoting the shareholder value theory, we will not make much progress on the 10/90 gap.  Ironically, the realization that even rich generic managers may no longer be protected from some of the deadliest diseases that used to only afflict the poorest people in the world may have an effect on this problem.   

As I have said before,  true health care reform would put in place leadership that understands the health care context, upholds health care professionals' values, and puts patients' and the public's health ahead of extraneous, particularly short-term financial concerns. We need health care governance that holds health care leaders accountable, and ensures their transparency, integrity and honesty.

But this sort of reform would challenge the interests of managers who are getting very rich off the current system.  So I am afraid the US may end up going far down this final common pathway before enough people manifest enough strength to make real changes.

ADDENDUM - This was re-posted on the Naked Capitalism blog


Anonymous said...

"a viral disease that is relatively easily spread" - really? How long did this particular epidemic has lasted so far? About 6 months, right? During this time about a 1000 people caught it in countries that have 30 million people. Does it look like rapid spread to you?
Ebola spreads by contact with bodily fluids of people who show symptoms (and for some time afterwards). It is not infectious during incubation period. Yes, infected people sweat, vomit an bleed so caretakers (like relatives in Africa) are likely to get some of infected material into cuts in the skin or mucous membranes e.g. eyes, but with strict isolation and hygiene Ebola is not likely to spread.

Compare it to H1N1 flu that infected millions an killed 25,000 (and not just those with weakened immune system, H1N1 killed young and healthy) in a couple of months. Sure it didn't have a staggering mortality rate of Ebola, but when so many people are infected a small mortality rate is likely to result in more deaths than a relatively rare disease with high mortality rate.

Are you willing to work for free? Why do you expect others to do it? Drug development costs money. Clinical tests cost money - and how are you going to test vaccine or drug for a disease that only affects a small number of people? How would you even run clinical trials? Even in Africa there are diseases that kill a lot more people than Ebola every year e.g. Malaria and AIDS among other diseases. Should a finite number of resources be shifted towards a disease that up till now have only had sporadic small outbreaks in remote areas?

As to Hepatitis C - how many people developed cancer as a result in total? Yes, only a small percentage of Hepatitis C patients develop cancer, but since the total number of people who get it is high, so is the total number of people who get cancer. Compare that to the total number of people that died from Ebola. So why should the researchers time and money shift from diseases that kill millions annually (including in Africa) to one that killed under a thousand?

Incidentally, Ebola isn't the only hemorrhagic fever. Marburg is a virus very close to Ebola and with similar mortality rate (even though mortality rate in a Germany outbreak was much smaller, the outbreaks in Africa resulted in mortality rates closer to Ebola). There is Lassa fever - not as high mortality rate as Ebola, but nasty too. Then there is Dengue which is very close to our shores and in some percentage of people causes hemorrhagic symptoms. Sure it's not as deadly as Ebola, but given that it spreads by mosquitoes, it infects a lot more people. Why according to you the researchers should've picked Ebola which until recently only had small sporadic outbreaks affecting hundreds of people out of all those other diseases? Why don't you create a list of diseases where you think the research money should go and see how far Ebola will be on your list?

Roy M. Poses MD said...

Anonymous of 12 August, 2014 at 1:42 PM, whoever you are -

"Relatively easily spread?" - Note that I certainly did not say "very rapidly spread." It seems that Ebola is a lot more easily spread than, for example, hepatitis C or HIV (which are most commonly spread through injections, e.g., of drugs, contaminated blood; and sexual contact.) Also, I would note that no one knows how long the current epidemic will last, and how many people it will ultimately affect, so it is possible the ultimate spread will be more than 1000 people in countries with 30 million population.

Note further that I didn't compare Ebola to H1N1 flu. I compared it to hepatitis C.

I would prefer not to work for free. But what does that matter? I never suggested that anyone should work for free.

Obviously drug development does cost money. But how much money does it cost, and how much should it cost, and how should spending money on development of different drugs for different uses be prioritized?

"Should a finite number of resources be shifted...?" I certainly was not suggesting infinite resources should be shifted. But some resources maybe should have been. Note that while Ebola previously only occurred in relatively remote areas, increased transportation in Africa, and increasing availability of international air transport surely suggested that Ebola could spread further.

"As to hepatitis C" Note that because most people with chronic hepatitis C infection do not develop severe complications, treating everyone who has such an infection means treating lots of people who could not benefit from treatment, but who will still suffer side effects and incur monetary costs from treatment. Of course, if we could predict who is likely to suffer a severe complication from hepatitis C, then we could treat only those people, and thus use treatment more efficiently. I wonder if a lot of resources are being used to develop tests to predict those most likely to suffer these complications, when successful development of such tests would threaten pharmaceutical company revenues?

Hepatitis C treatment also seems to be consuming huge resources not because drug development costs were so high, but because the manufacturers of treatment have so far gotten away with huge profit margins, way beyond anything that has to do with drug development costs. A rerouting of a small fraction of the money being used in the US to pay for Sovaldi to Ebola research would result in a big increase in money spent on Ebola research.

I hardly suggested that only Ebola research is worthy of increased resources. True, there are many other "tropical" infectious diseases that could end up more widely spread. They may also be worthy of more attention. There are also lots of other serious diseases that so far inspire the use of few resources, mainly it seems because their victims tend to be poor. Lots of other people have created lists of these diseases. I don't claim to be an expert in the area. If you are interested, look at the WHO site for neglected diseases as I posted:

Finally, note that we have always allowed anonymous comments on this blog, mainly to help whistle blowers and allow comments that might discomfit the powers that be. But the current "anonymous" seems to be defending the status quo. I wonder if he or she would be willing to identify himself/ herself?

Anonymous said...

Hi I was just wondering what your thoughts on Chronic Fatigue Syndrome are and if you think there will ever be biomarkers and a drug developed specifically to treat it. There could be a ton of money made off a drug to treat CFS so why aren't drug companies interested?

Anonymous said...

Those that work at these pharma firms are ethically compromised. They rationalize their company's actions and the actions of the industry. This absolves them of any guilt.

So its understandable to hear comments like those of the anonymous poster above. And of course there is some truth in the post as well. Its a matter of degree to which it's profits uber alles.

No matter how one looks at it, all of this medical stuff is essentially profiting from the misfortunes of others and there should be some limit on that sort of thing.

Its like the murder in Ferguson right now, its a question of stepping over a bright line, or at least a bright enough line for uninvolved folks to see.

Sovaldi should generate some profit and should increase the value of the corporation, but its the extent of that which is distressing.

Werry Adnan said...

I never thought before the main reason for this problem is because no enough fund to develop research.. It is kinda sad that most people jump to this industry only focus on business..