Available on youtube at address in referenceIn acknowledgement of the world wide “Occupy Wall Street’ movement this talk is on ‘Occupy Medicine’
Specifically it is about vaccines for 99% versus profits for the 1%
There is the story of a sales person who went to a villager and asked to buy a donkey.
The villager said. I have a donkey. I need the money. You can have my donkey. It will cost $100.
The salesman paid the money and the villager promised to deliver the donkey on the following day.
However the donkey did not arrive on the next day.
The salesperson went to the villager and asked why the donkey was not delivered.
“I am very sorry” said the villager, “ but the donkey died’
“ The donkey died?” said the salesperson – “Give me back the money”
“ I am sorry” said the villager, “I told you I needed the money desperately. I am afraid your money is spent’
“The give me the dead donkey” said the sales person.
“You want the dead donkey?” asked the villager – “What can you do with a dead donkey?”
“That is none of your business”, said the salesperson. “Just get me the donkey”
The next day the villager got a cart and delivered the dead donkey.
The villager was curious. 2 weeks later he went to the salesperson and asked him just what he did with the dead donkey.
“ I sold him for a profit of $898 said the salesperson”
“Well not sold him. I raffles him for $2 a ticket. I sold 500 tickets”
“You raffled a dead donkey’ asked the villager incredulously, “ and no one complained?’
“Well” said the salesperson “one chap did complain. The guy who won the lottery. I gave him back his 2 dollars”
I am reminded of this clever salesman when I think of how vaccines are sold today
We were told that 250,000 die of hepatocellular carcinoma due to Hepatitis B in India each year. This was published in the journal Health Economics by Mark Miller who gives his affiliation variously as CDC Atlanta and WHO Geneva.
Data from well maintained, population based cancer registries at that time, suggested the figure was around 5000 deaths. So I wrote to the journal and asked to see the model Miller had used to arrive at his figures.
Miller wrote back that a model ‘stratified by income group and geographic region’ was used and it was available on the CDC web site. There was no model on the web site.
So how would the number 250,000 deaths have been arrived at?
I figured that they may be projecting the mortality rates of Taiwan male hepatitis B carriers on the population in India – both male and female.
1 in 4 male carrier in Taiwan die of hepatic cancer. This is a world record. It is 3 times the mortality rates among Taiwan females. It is 17 times the mortality in Canada. We now know that this is due to a strain of the virus in Taiwan.
India and this is what you get.
About 4% of Indians are carriers. If 1 in 4 of the 4% is to die of hepatic cancer then 1% of all our deaths must be due to Hepatitis B cancer. 1% of deaths in a population of 1 billion is 200,000.
We wrote this up and sent it to the Lancet saying Miller’s model is not available but this appears to be how to arrive at that figure. The Lancet published it.
I then wrote to the journal Health Economicsasking that in the light of the Lancet publication, Miller must either publish his model or otherwise retract his paper.
Prof Miller wrote – and this published in Health Economics – that the model was ‘lost’.
The paper has not been retracted as yet.
H influenza b (Hib ) disease. The incidence of Hib in Asia we know is about a tenth of what it is in the West.
An editorial in the Bull of the WHO wonders if the vaccine is really needed in Asia
Pre-vaccination titers were consistently high in Asia. This study from Turkey showed that antibody levels rise with age – If it were all due to passive immunity the antibody levels should fall with age.
There is another phenomenon.
Post vaccination, the antibody titers rise to levels some 10 times higher than that seen in the West. Such levels are not seen with primary immunization - only with booster immunization. This suggests the children were already having active immunity before being vaccinated.
There are animal models to explain why Asian were naturally immune to Hib. Many bacteria like the E.coli have cross reacting antigens and infection with one protects against the other. E coli is so common in Asia and is a commensal in most children and this could be protecting against invasive Hib disease.
However vaccine manufacturers are not easy to persuade. They are convinced that the poor culture rates of Hib invasive disease in India relates to the fact that we don’t know how to culture the organism. The culture medium needs Isovitalex they say.
So the Invasive Bacterial Infection Surveillance Group (IBIS) decided to do the cultures themselves using the best culture media, in 6 of the biggest hospital in India. They did this continuously over 4 years and all they got was 125 cases. The numbers were so abysmally low that it was necessary to provide an explanation in the journal article reporting the study. They suggested the reason for the low numbers may be related to poor access to these large hospitals and Hib patients may all be dying quietly at home. They suggested a community based study to look at the real picture. Community studies are exorbitantly expensive but the WHO funded the study
The community study found an incidence of Hib meningitis of only 7/100,000.
This papers now suggests other reasons for the low numbers. Among them they admit that there may be natural immunity to Hib in
The vaccine manufacturers are not happy with that explanation. Now culture media cannot be blamed, poor access to hospitals is not the cause – a new reason for the poor culture rates needs to be found. Well can it not be that India is a country of quacks and doctors who are all prescribing antibiotics left right and center. Under such circumstances culture rates will be low. The only way to know would be to do Probe Studies
Probe studies identify reduction in clinical disease after immunization. All the disease the unvaccinated have over and above the vaccinated must be due to Hib. No culture proof is needed.
Lambok Study was done in Indonesia.
It was an excellent study. 55000 children were randomized to receive Hib or act as controls.
This was a double-blind study.
There was active case surveillance. Reported in 2005
Unfortunately in this study there was more Pneumonia among the vaccinated – not statistically significant, but more pneumonia in those vaccinated
There were more children with pneumonia in the vaccinated group than in the control group. It did not however reach the level of statistical significance.
This was published in 2005
Then we have the Bangladesh probe published in 2007
This study was not as rigorous as the Indonesia study.
There was no blinding – no randomization. There was no active surveillance.
It was an incident case-control study. 35% had received the vaccine. There were 475 cases of pneumonia from this population of 68,000.
There was no significant difference in either of the end points – not for meningitis or pneumonia.
This was published in the journal Pediatric Infectious Disease but who among the public reads medical journals?
Let us see what the press release after this study, says.
Believe it or not: this is what the press release said:
Study shows Hib vaccine could prevent about 1/3 of life-threatening cases of bacterial pneumonia in Asia.
The press release was signed jointly among others by the WHO, GAVI, USAID and Johns Hopkins.
This was exposed in both the BMJ and the Indian Journal of Medical Research. None of the organizations have refuted this allegation of deliberately misleading the public in this press release.
There is no hidden agenda. The cost of the vaccine in the USA is $5.60.
Price can come down only if Hib is part of EPI internationally. This was published in Nature Medicine and the Lancet. By inference, poor countries must include this vaccine in the EPI that they do not need, so the price of the vaccine can come down in the West.
Studies in Canada have shown that the vaccine has eliminated Hib in the country but there is proportional increase in non-B H. influenza strains causing invasive H influenza disease in the post-Hib vaccine era.
The pneumococcal vaccine. The vaccine costs Rs 12,000 per child for 3 doses.
According to what has been published in the WHO Bulletin it reduces 3.6 cases of pneumonia per 1000 children vaccinated.
The vaccine doubles the chance the child will get asthma, according to this article in the New England Journal of Medicine.
According to this Lancet article, in India the vaccine costs Rs 12,000 per child and
Vaccinating 1000 children costs Rs 12 million. On the other hand treating 4 cases of pneumonia will cost Rs 40 if WHO recommended Septran is used. So we spend Rs 12 million to save Rs 40.
Assuming the prices come down to a tenth of the present market rate. It will cost Rs 1.2 million to save Rs 40. Good value for money?
Treating 4 cases of pneumonia will cost Rs 40 if WHO recommended Septran is used
Where the 7 valent vaccine was used, those strains have come down but it has been replaced by 19A. Previously the pneumococci were nearly all Pencilline sensitive. The new strain is often Pencilline resistant. So now a 13 valent vaccine that includes 19A. We await results on what new strains will emerge. There are about 100 known strains of pneumococci.
Briefly, on the rotavirus vaccine. Studies have shown that there is continuous re-assortment between bovine and human rotavirus strains in India; that the strain is different in different places and at different times in the same area. There is not one study to show that the vaccine reduces diarrhea in the country. Yet it is promoted in the country.
There are so many wonderful programs of disease control. How does one decide what programmes to chose. Take this hypothetical case study. You have Rota virus control that costs Rs 200 crores for implementation nationwide. It saves 1 life year per Rs 20,000 spent. There is polio control costs Rs 350 crores and saves 1 life year per Rs 10,000 spent. TB control costs Rs 700 crores and it saves 1 life year per Rs 5000.
Assume you have a budgetary constraint of Rs 1000 crores. What programmes will you chose and why?
I am using heath economic terms here in a non-technical manner, for easy understanding. We need to rank the programmes in the incremental order of cost-utility ratios. TB is most cost effective as it saves a life per Rs 5000 spent. That will be the first priority. That will use up Rs 700 crores from the budget. We are left with only Rs 300 crores. We must spend it on polio control.
Rota vius control will not feature in our plans although the whole programme costs only Rs 200 crores.
If we spend on Rota virus programme we have Rs 200 crores less for TB control. For ever life we save from Rota virus, we will be losing 3 extra lives to TB. This is why it will be unethical and even criminal to divert money for a less cost effective scheme when there are more cost beneficial uses for the resources.
In India 50% of the population don’t receive the basic EPI vaccines costing Rs 30/ child. Vaccinating with the HPV vaccine costs Rs 9000, Rota virus cost Rs 2000 and the Pneumococcal vaccine costs Rs 12,000 per child. From the community perspective will use of these newer vaccines be ethical?
Let us look at it from an individual perspective. We have a vaccine that costs Rs 12,000 but the marked price on the vials, paid by the patient, includes a kickback of Rs 3000 for the doctor who administers the vaccine. The vaccine does little good (only 3.6 cases of pneumonia reduced per 1000 vaccinated); it doubles the risk of asthma (1.4 extra cases of asthma for every 3.6 cases of pneumonia prevented); and the community risks the emergence of antibiotic resistant strains. Can it be prescribed ethically to those who have the money and can afford to pay?
If these vaccine are so bad, then how come the WHO is promoting it? How come anyone uses it? How can it be promoted?
Half truths areused to sell the vaccines. The following are statements from the SAGE report of the WHO recommending pneumococcal vaccine. 10.6 million children under five years of age die each year. Pneumonia, leading cause of mortality among children in developing countries. Pneumonia is a vaccine preventable disease.
The unsaid part of this truth is that the vaccine is against only one bacterial pathogen among the numerous agents that cause pneumonia, and that against only a limited number of strains of that bacteria. It is dishonest to pretend the vaccine can prevent all pneumonia
Another half-truth is that Pneumococcal vaccine protects against 80% vaccine-strain invasive-disease (VS-IPD). That is straight from the Cochrane meta analysis.
The other half of the truth in the Cochrane report is that there is no reduction in all-cause mortality with the vaccine, but this is not highlighted. The incidence of vaccine-strain invasive-disease was so low - the absolute risk difference (ARR) is only -0.002 and the number needed to vaccinate to prevent one case of pneumonia was 500 in this analysis.
Misleading statistics are what we need to understand. A risk reduction (RR) of 50% sounds good for a vaccine.
Patients and doctors are easily convinced with this figure. This article in Clinical Oncology shows how it can be misleading. Suppose risk comes down from 4% to 2% the RR is 50%. Another accurate way to describe the benefits would be to say that the intervention affords 2% reduction in absolute risk. Only this is less likely to convince patients to take the treatment.
Take the instance of yellow fever vaccine. Assuming it has 100% efficacy against yellow fever. We in India would not use the vaccine in a national immunization programme because the disease is non-existent here and the absolute risk reduction is zero.
Let me elaborate on this statistical concept because it is crucial. Relative risk (RR) is the ratio of the two risks. If the risk of disease comes down from 2/1000 to 1/1000 the RR is 50% and it can be said to halve the risk.
To calculate the absolute risk reduction (ARR) you do not need any new data to be collected. Here instead of a ratio, one risk is subtracted from the other. The ARR in this case is 0.001. ARR is very useful because the reciprocal of ARR is the numbers needed to treat (NNT) to prevent one case. In the example above the ARR is 0.0001 and we can easily calculate the NNT as 1000 children vaccinated to prevent one case.
Thus using the same raw data if ARR is reported it allows one to calculate the total cost to prevent one case. This is very useful. RR is quite useless without data on the frequency of the problem in the community
The BMJ has been pleading for this change for some time. A chief editor Godlee has written in an editorial entitled ‘Absolute Risk Please’ where she says that impressive sounding reductions in relative risk can mask much smaller reductions in absolute risk. Clinical decisions must be based on absolute risk (AR) rather than relative risk (RR).
So what can we do to avoid buying a dead donkey?
We need a resolution in the World Health Assembly along the lines recommended by the BMJ. For all intervention being recommended to enhance child survival, the WHO and other agencies must always report efficacy in terms of 'absolute risk reduction' (NOT Relative risk (RR)) so that member states can calculate cost benefits easily.
There can be no logical objection to deny this demand.