Rethinking global access to vaccines
BMJ 2008; 336 doi: https://doi.org/10.1136/bmj.39497.598044.BE (Published 03 April 2008) Cite this as: BMJ 2008;336:750
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I have read the article about use of newer vaccine in large extent in developing country like India.now question arises in my mind is whether to use these vaccine in India where poverty is the main concern,death due to rotavirus are significant but it mostly affect the severely malnourished child in whom there are so many other causes also, that lead to death..here people have no money. they even cant purchase a soap to take bath how can they afford the cast. Second thing is rotavirus strains,the strain that is present today may be different tomorrow????
Competing interests: None declared
Competing interests: No competing interests
When we go through articles the like of the one by Dr Chokshi, we singularly miss the viewpoint of the patients or the parents whose children would be the subjects.
Had Dr Chokshi cared to ask a few Indians whether they would like their children to be vaccinated with the Rotavirus, the Hep-B or the HPV, after informing them of all the probable side effects, he would have been forced to rely more on the public health measures he derides rather than promote expensive and unnecessary vaccines.
Why does Dr Chokshi forget that there is no informed consent in India, no compensation scheme, and no surveillance system in place to follow up on vaccine adverse events?
For any responsible physician who would like to see the people healthy these are the bare minimum precautions to take.
Dr Chokshi is sadly out of touch with the ground reality in India where poor families face ruin burdened with vaccine damaged children. The plea of well meaning doctors seeking to identify and compensate these unfortunate victims fall on deaf ears.
The real challenge to the vaccination programme in India is not the availibility of vaccines or the reluctance of vaccine manufacturers to market their products in this country, the challenge is restoring the confidence of the public on a system that only makes them sick and more sick.
The vaccine manufacturers are only too willing to jump at the opportunity of India's "huge untapped market" and the more than willing vaccine pushers who are offered huge commissions and foreign jaunts.
We would request Dr Chokshi et al to kindly visit India and talk to the senior physicians and epidemologists before coming to any hasty conclusions.
This small step will help save millions of lives.
Regards, Jagannath.
Competing interests: None declared
Competing interests: No competing interests
The paper " Rethinking Global access to vaccines" makes a strong advocacy for public investments in developing an evidence base by the developing countries for the development and appropriate use of newer vaccines . The reality in the developing countries is far different. This 'infrastructure' of research and information systems for assessing the disease burden, the potential for the newer vaccine to impact on the specific disease burden and effective surveillance for potential negative effects of the vaccines is entirely absent in the developing countries. The creation of such an infrastructure requires the complete revamping of the public health systems in the developing countries. Those who promote the 'vaccines' as the most cost effective interventions for the poor, never take into account the costs of erecting the health systems which can deliver the vaccines and monitor its efficacy and safety.
From the perspective of a developing country health workers, including the doctors and health planners, the efficacy and safety of the vaccines are 'gospel truth' and they are not trained to think in terms of developing the indigenous evidence base for this. There is no doubt that some of the developing countries' pharmaceutical manufacturers have been able to manufacture the newer vaccine at a very low cost. However this does not necessarily proves that similar capacity can be developed by the pubic health delivery systems in these countries, for the tasks expected from it.
Therefore, it is inevitable that developing countries health workers and health systems will continue to be dependent on the research and evidence base developed in the developed countries to find the rationale for the use of the newer vaccines and other newer medical technologies, in the near future. The merits of this dependency are a different issue altogether.
The paper also quotes Amartya Sen to throw light on the opportunities that open up for the poor in the developing countries for coming into contact with modern health systems by the delivery of the vaccines. However, the poor in the developing countries have competing needs for food, shelter, water, sanitation and education. In real life the vaccines do not come to them as additional opportunity but as a competing opportunity with their other needs. One evidence of this is the widely prevalent malnutrition in children in India, due to lack of health education of the mothers, since the health workers are too busy in delivering vaccines. Therefore we have some improvement in vaccine coveragae in the last two decades in India, but no evidence of decline in malnutrition in the children.
Therefore the advocacy for the global access to newer vaccines needs to be better informed by the ground realities of the health systems in developing countries and the real opportunities for the poor.
Dr. Onkar Mittal
Competing interests: None declared
Competing interests: No competing interests
The authors of this paper (1) begin with a misleading and incorrect statement attributed to the WHO that “inadequate access to vaccines in low and middle income countries results in more than two million deaths each year”. The reference they cite (2) is 243 pages long but we were not able to find this single sentence or even pages from which this statement could be arrived at. In fact the whole of paragraph 1 of the paper is meant to appear logically structured whereas they are unconnected and disparate sentences strung together. The authors’ statement that two thirds of deaths (due to inadequate access to vaccines) occur in children under the age of 5 followed by a statement on Hepatitis B and Hib vaccines now being used in low and middle income countries is to mislead the reader into interpreting that most of these two third deaths are due to hepatitis B and Haemophilus influenzae.
Mere availability of vaccines in the market that are “well established” in one country cannot be the reason why it should be used in another where the disease profile does not warrant its use. Since the mid 1990s, the vaccine lobby, under the aegis of the WHO, has been pushing the use of both Hepatitis B and Hib vaccines for universal use in India. This manoeuvring has succeeded in the case of Hepatitis B only because of funding pressure from GAVI and other donors. This was despite the recommendation from Indian experts. The argument put forward by the authors that Hepatitis B vaccination is cost effective in Gambia, a country with high prevalence of Hepatitis B, does not hold for India. The Indian Medical Association after a consultative meeting held in May 2006 came to the conclusion that cost-efficacy of universal immunization with Hepatitis B needs to be reevaluated considering the low point prevalence (2.1%; 95% C.I 1.8-2.5) and a low chronic carrier rate of 1.6 % (3).
The authors argue that through vaccination, a health infra-structure can be built and give the example of polio eradication in the Americas. However, in the case of India, the obsessive attention to this single disease through the vertical Polio Eradication Programme has led to the deterioration of public health services, particularly in the uptake of other essential vaccines such as DPT (4).
Fretting at drug regulatory controls is not new in the history of pushing hazardous, inadequately tested products from the west into developing countries. The argument put forward to the authors that the increased risk of intussusception with rotavirus vaccine would make this “side-effect” “more tolerable” in countries with higher rate of morbidity from rotavirus shows the little concern the authors have for the lives of children in such countries, for such “side effect” of intussusception would translate into deaths in these countries. Their argument for Gardasil too does not reflect the data that is accruing from high income countries where it has been approved despite serious adverse reactions including deaths (5, 6).
The authors state that those who “believe that ensuring supplies of food and clean water and building roads will do more for public health than isolated interventions like vaccines”, imply that such ‘beliefs’ are unfounded. We suggest that the authors (both the student and the instructor) would do well to brush up on some history by reading up on how in the USA, the sharp decline in mortality rates due to infectious diseases, the major cause of death in the early part of the 20th century in the USA, took place before the specific medical technology for each of the infectious disease developed and the resons ascribed to this decline (7).
The authors once again mislead the readers by evoking Amartya Sen and quoting him out of context to justify their stand of technological interventions being superior to working on the social determinants of ill health. The paper brings to the mind the oft repeated quote “if they have no bread, let them eat cake”, wrongly ascribed to a French queen. The student and the instructor, authors of this paper, would do well to live in a low income country for a period sufficient to appreciate the realties of the people living there before they arrogate to themselves a right to advice, an advice that sounds so much like what would be expected from the vaccine manufacturers lobby and their front organizations.
References:
1. Choaski DA, Kesselheim AS. Thinking global access to Vaccines, BMJ 336;2008;750-75
2. World Health Organization. World Health report 2005:make every mother and child count. Geneva: WHO, 2005.www.who.int/whr/2005/en/index.html
3. Indian Medical Association and Plan international (India). Report of the National Consultative Meeting on Hepatitis-B and Polio Eradication Intiative. New Delhi 14th May 2006
4. Planning Commission. Tenth Five year Plan (2002-2007).vol II. Sectoral Policies and programmes, Family Welfare, Government of India, New Delhi undated.
5. 5. Sikora K, Bassett K. Hundreds get sick from Gardasil cancer vaccine. www.news.com.au/story/0,23599,22860011-421,00.html accessed 10.4.08
6. Eggerston L. Adverse events reported for HPV vaccine. http://www.cmaj.ca/cgi/content/full/177/10/1167 accessed 10.4.08
7. Mckeown . The Modern Rise of Population. New York, NY Academic Press, 1976 8.
Competing interests: None declared
Competing interests: No competing interests
Polio is a crippling disease and efforts are on to eradicate it not only in India but globally. The much advertised and popular "Pulse Polio" programme is a decade old and was designed to eradicate polio by 2000, postponed to 2005. The Union health minister announced in Parliament that the goal of eradicating polio is no where to be visualised, even at the end of 2006. Furthur just few days back the anounced that the Pulse Programme needs review (http://www.ndtv.com/convergence/ndtv/story.aspx?id=NEWEN20080046361)
This was the largest health programme ever to be carried out in the world and had the support of World Health Organisation, UNICEF, Centre for Disease Control of US and Rotary International. As the goal of eradication has failed, it is time to take stock of the situation and start analysing the reasons for failures. The Indian Health Minister now seems to have realised it.
But what is interesting to note is that the Indian Medical Association (IMA), a rather conservative nevertheless the largest professional body of allopathic doctors in India, has come out with an independent report on the drawbacks and reasons for failure of pulse polio. One of the fears expressed by this August medical body is with regard to the number of cases of paralyses that have been happening in spite of children having been vaccinated several times. Thus by increasing the number of polio vaccines for every child "does not seem to be stopping the transmission of polio and needs to be reviewed", points out the IMA report.
This has been the largest mobilisation of people for public health reasons.
More than Rs 5,000 crore has already been spent. But, the pressure for pulse polio is so much that high "priority health problems have receded to the background", notes the IMA report. For example if child has snake bite and needs immediate attention, there are no personal to attend, as the entire medical team is busy with pulse polio programme.
A major set back to the pulse polio programme has been from the increased cases of Acute Flaccid Paralysis (AFP). In fact India has recorded highest number of such paralyses. The global average incidence of AFP is one in 1,00,000, but in India the incidence has risen to 12-13 per 1,00,000 with the implementation of the pulse polio programme. Incidence of AFP increased from 3,047 cases in 1997, when polio eradication had just begun, to 27,000 cases in 2005. It is highly suspected that there exists a connection between vaccinations and rise in AFP. There can also be no denying that AFP has hit children who have been vaccinated.
Injectable vaccine
While some experts continue to advocate that the injectable form of polio vaccine should be administered to overcome the AFP, the cost is prohibitive. When imported the injectable vaccine is 25 times more costly than oral vaccine. The injectable form has an advantage over oral in that it is less sensitive to temperature fluctuations and is less likely to be inactivated by breaks in cold chain. However, injectable form affords little herd immunity and so literally every child will need to be injected with the vaccine before we can eliminate polio. But in India it has not been possible to achieve 100 per cent immunisation with an easy-to- administer oral vaccine — the coverage will be much worse if we approach these children with a syringe and needle.
Competing interests: None declared
Competing interests: No competing interests
The authors of this piece explore reasons for why ‘effective’ vaccines are unavailable in poorer countries, and come up with several plausible explanations. However, they miss the basic reason which is that most wealthy countries demand a solution (vaccine) for infectious diseases that assume public health significance. This demand drives the development of vaccines that are then manufactured and marketed. On the other hand, poorer countries fail to express a demand, and should they do so, are largely ignored. This explains why there is scant attention to important issues (such as improving the measles vaccine, preparing polyvalent combinations that incorporate the affordable DPwT rather than DPaT, providing an efficacious as well as effective tuberculosis vaccine) but supra-normal focus on ‘new vaccines’ irrespective of the desirability and feasibility of their administration in developing countries. What is worse is that many manufacturers have realised the potential of marketing in developing countries (owing to large population size and variable spending power) and are ruthlessly exploiting the weak decision-making systems there to aggressively promote products that are often not required.
The following points in the current piece need attention:
1. The authors state that “difficulty in disseminating well established vaccines casts doubts on our ability to promote widespread use of new ones…” In fact, the exact opposite is being witnessed in most developing countries today. Although coverage with vaccines such as DPT and measles has still not reached levels required to eradicate/ eliminate/ control these ‘old’ problems, there is aggressive “promotion for widespread use of new vaccines” such as Pneumococcal conjugate vaccine, Varicella vaccine, Influenza vaccine and more recently Rotavirus vaccine and HPV vaccine. What is more unfortunate is that this promotion is not being done by manufacturers alone, but also directly and indirectly by trusted organizations such as WHO, national bodies of experts and perhaps publications such as the one being discussed.
2. Although “empirical analyses… of polio eradication in the Amercas, have documented how immunisa¬tion programmes can strengthen the infrastructure of health systems”, the opposite is also true in many developing countries notably India; where single minded focus on the polio eradication initiative has actually led to disruption of delivery and community access to existing health services, including vaccination. This accounts for the rising numbers of conventional vaccine preventable diseases, against the backdrop of declining polio cases, despite the documentation of ‘improvement’ in vaccination coverage from about one- third to one-half. Nevertheless, the contention that immunization programmes can strengthen health systems, has some merit if the immunization programme targets a relevant public health problem, delivers tangible results within a finite time period, is cost-effective and is user-friendly (incidentally, the current polio eradication initiative in India fails on all counts).
3. The table on “development and dissemination of rotavirus and HPV vaccines” (replete with brand names and supporting institutions) appears to be intended to “promote widespread use of the new vaccines”. If the authors intended any other outcome, it is not discernible.
4. Likewise, the purpose of the photograph of an infant receiving nasal/ naso-pharyngeal CPAP (continuous positive airway pressure) for a respiratory problem; but with a caption promoting rotavirus vaccines is unfathomable.
5. To the question whether, “vaccines must be developed for and approved by wealthier countries”, another relevant question is “whether this development and approval must always depend on clinical research carried out on people in poor/ developing countries”?
6. The authors’ perception that “pharmaceutical manufacturers receive the vast majority of their revenues from wealthier countries” need not necessarily be true since vaccine manufacturers are doing brisk business even in smaller countries, by virtue of a large population base, a proportion of whom are led to pay for expensive vaccines (whether required or not) by the ‘widespread promotion activity’ alluded to by the authors.
7. For some strange reason, there has been a general perception that the basic tenet of health-care intervention, “Primum non nocere” (first do no harm) does not apply to developing countries when (and where) the burden of natural disease is high. This is evident from the fact that this argument has been used by the WHO in endorsing the administration of an unprecedented number of OPV doses in India (5.6 billion to date) with scant concern for vaccine associated paralytic poliomyelitis (VAPP), initiation of monovalent OPV against type 1 (mOPV1) without regard to its impact on circulation of type 3 virus and of course, the contention of the authors of the current piece that the “higher rates of morbidity from rotavirus associated diarrhoea may have made the low risk of that side effect (intussusecption) more tolerable” in developing countries.
8. It is not clear how the authors suggest that “the public health community should better regulate intellectual property so that new vaccines can reach the people who need them” suggesting that this is a mere rhetorical statement.
9. Although the WHO prudently restrained itself from recommending rotavirus vaccines for all regions of the world on the grounds that trial data was not available from Asia and Africa; it is not clear why this prudence has not been evident in its recommendation for other vaccines such as the Pneumococcal conjugate vaccine and monovalent oral polio vaccine (mOPV1).
10. The authors have omitted to mention the affiliations of the four persons mentioned at the end of their paper; this needs to be clarified.
Joseph L. Mathew
Advanced Pediatrics Centre,
PGIMER,
Chandigarh, India 160012
Email: jlmathew@rediffmail.com
Competing interests: None declared
Competing interests: No competing interests
Immunization has been rightly acclaimed as a major public health measure that has prevented many deaths and avoided much misery. The elimination of small-pox, the near elimination of polio, and the substantial reduction in measles, diphtheria, tetanus and whooping cough during the last several decades have been celebrated as great success stories of modern medicine. Apart from such obvious medical benefits, any analysis of cost and benefit of these vaccines will definitely show their financial benefits. The adage that prevention is better than cure is so true in the case of immunizations. As such, the medical community and the public at large welcomed most of those vaccines with enthusiasm and without questioning their medical and financial benefits. Their medical usefulness and financial benefits have been well proven in most countries and especially in poorer countries.
The newer vaccines coming into the market may be medically safe and effective. But their cost effectiveness is being questioned even in the rich developed countries where they were first introduced. Most of the newer vaccines are against diseases which are not as severe as the previous ones and the effect of such vaccines on child survival is only marginal at best. They are mainly against diseases which are mostly inconveniences rather than debilitating or life-threatening. The best example of such a new vaccine is the one against Rotavirus infection which cases diarrhea in children. An analysis of the medical benefits of the Rotavirus vaccine in the U.S.A shows that it may prevent 13 deaths per year. But the main reason for using the vaccine in USA is the financial savings from reduced hospitalization and visits of the doctor. Similar analysis of the same vaccine will definitely show that even though it may have marginal health benefit, the financial cost will be against the use of the vaccine in India. It is the very high charges of hospitalization and visits to the doctor which makes the vaccine cost effective in USA. Since those costs are much less in India, any prudent analysis will show that the vaccine is not suitable for Indian conditions. But these considerations are never given a serious thought and study when a new vaccine is introduced in India. Many of the newer vaccines introduced in India, if analyzed rigorously will probably be shown not to be cost effective under Indian conditions. As the science of political economy is about the most prudent and useful allocation of restricted resources, any new vaccine being introduced to this country should undergo such analysis before its widespread use is encouraged.
The vaccines against chicken-pox and Hepatitis A, if subjected to such cost/benefit analysis will be shown to be not much beneficial under Indian conditions. Chicken-pox is a relatively mild disease in children and produces almost complete lifetime immunity. But in adults it could be a serious disease causing severe disability and even death. A vaccine for chicken-pox was developed in Japan several years ago, and it was not introduced into the western countries because of many potential problems. Apart from its cost, there was not much certainty about the duration of immunity after the use of chicken-pox vaccine. The fear was that if the immunity from vaccine is not for lifetime, and if it diminishes as one gets older, the chances of getting chicken-pox during adulthood may be increased and thus cause more complications. Such fears have to some extent been proven to be true, as now it is known that the immunity from chicken-pox vaccine wanes as years go. So now it is recommended to take booster doses for chicken-pox vaccine after the age of 10 years. It is not certain for how long immunity will last after such booster doses. In such an uncertain scenario, it may not be prudent to recommend chicken-pox vaccine routinely to children in India. There is also another factor to be taken into consideration. Unless a large percentage of children are vaccinated, the herd immunity of the children in a community may not increase and as such many children may not get the disease during childhood. They will be prone to get the disease during adulthood with all the complications. There are mathematical models showing that vaccinating only a few percentage of the children may be deleterious for the whole community. If only the rich are vaccinated, the poor may not get it during childhood and may get it during adulthood. These public health effects of such vaccines have to be analyzed completely before they are recommended for routine use. There are still rare conditions where children may have to be vaccinated – like children who are immunosuppressed or suffering from certain diseases.
The vaccine against Hepatitis A also probably comes under the same category of costly vaccine for a minor illness. Hepatitis A is a generally mild disease especially in children. Most children recover from it very soon without much problem. It may be slightly more symptomatic in adults; but most adults also recover from it without much problem. As it is transmitted through water and food, providing good drinking water and clean food is more important in its prevention than the costly vaccine. Such public health measure as clean water will prevent so many other diseases like Typhoid, Cholera, Dysentery and other diarrheas.
India, Pakistan, Afghanistan and Nigeria are the only countries in the world to have endemic Polio still among its native population. Though the endemic cases of Polio are mainly limited to areas of Western Uttar Pradesh, India is in the embarrassing position of being the source of Polio infection to neighboring countries like Nepal and Bangladesh and even distant countries. As we proudly march towards being a leading nation of the present century, why are we still unable to overcome this problem which has been eliminated from most parts of the world, even from poorer countries in Asia and Africa? Are there reasons beyond just the failure of Polio eradication which can teach us some lessons regarding public health? Are there areas where our government, professional organizations and other NGOs could have done things different and better?
As a pediatrician, and being familiar with the activities and recommendations of some related professional organizations in this area, I feel that we have failed in our duty to do the maximum possible to eliminate preventable diseases with our limited resources. The recommendations of professional bodies during the last few years seem to have given less attention to common problems like Polio and Measles and given much more importance to the prevention of other rare and less severe diseases. The poor child in rural India was not the focus of attention of the professional bodies. The rich urban child whose parents can afford the new costlier vaccines for rare diseases were the focus of attention and areas of debate in the pages of the journals of professional bodies. There did not seem to be much interest in the use of cheap vaccines which do not drive the profit margin of drug companies, who seem to have driven the agenda for immunization recommendations. Their greed, rather than the need of the poor children of India, seemed to have attracted the attention of professional organizations which seemed to have been mere propaganda machines for drug companies.
There are several examples of such inappropriate attention to rare diseases at the cost of neglecting major public health problems. The problem of the continuation of Polio is well known and much discussed in the media. The failure to eradicate Polio is not due to any inherent problem with the vaccine itself but due to the failure of the routine immunization of all children. Most countries have eliminated Polio either by the Oral Polio Vaccine or the Injectable Polio Vaccine. Out inability to immunize most of the children is the major reason for our failure to eliminate Polio. But if one peruses through the pages of the Journals of professional organizations of pediatricians in India published during the last several years, one can see that the attention given to this problem is miniscule compared to the pages written about other vaccines against much rarer diseases.
And to add to the confusion, some professional organizations have come up with the suggestion that India should shift from Oral Polio Vaccine (OPV) to the Injectable Polio Vaccine (IPV). This is not only confusing by may even be counter productive. It is more costly than OPV and since it is in the injectable form, it will be more difficult to give routinely in a massive scale. When we have failed to give the easily given OPV universally, it is unreasonable to expect that we will be able to give IPV to larger number of children. The commercial interests behind the IPV promotion makes the motives behind the suggestion suspicious, given our past history of succumbing to such pressures.
Measles is still a big killer of children in India especially of poor malnourished children. And Measles is a disease which can be eliminated much easier than Polio as there are no other carriers of the virus than humans and when all children are immunized against Measles, it will be eliminated unless cases are imported from other countries. For full immunization of children, two doses of the Measles vaccine have to be given. As per the present Indian recommendations, only one dose is given to children at the age of 9 months. If another dose of Measles vaccine is given at around 15 months as part of the Measles, Mumps, Rubella (MMR) vaccine, these three diseases can be eliminated in a few years. But the professional bodies who make recommendations to the government on such matters have not yet recommended to include MMR in the national immunization programme. The Indian Academy of Pediatrics has officially recommended to the Government of India to initiate vaccination against Hepatitis B, before including MMR vaccine in the national schedule. The incidence of Hepatitis B in India has been shown to be not as high as it was thought to be, and as such the number of cases of carriers of Hepatitis B, and related complications like Cirrhosis of liver and Carcinoma of liver are much less than anticipated. Hence the cost – benefit analysis of the Hepatitis B vaccine in India is still debatable and including it in the national immunization programme may not be justifiable.
Another newer vaccine being promoted aggressively by the drug companies with the acquiesce of professional academies is the one against Haemophilus Influenza type B. It is true that infections, especially meningitis, caused by Haemophilus Influenza in young children are a very serious disease. It causes a high proportion of death and disability. Even though it is present in India, the exact epidemiology of the organism in India is not known and there are no large studies showing what is the real incidence of this infection in Indian children. Before having such robust data from India, the professional academies have recommended its use in India without calculating the risk-benefit analysis. Before it was introduced in USA, there was a clear understanding of the incidence of the disease there, and calculations had shown that its benefits are more than the cost of the vaccine. And the reduced incidence of Haemophilus infection in USA after the introduction of the vaccine has been shown to be as predicted and it has changed the epidemiology of infectious diseases of US children. But in India we have no robust data about its incidence before the vaccine was introduced and so there will be no comparable data to evaluate the benefit of the vaccine. And paradoxically, the vaccine is being used mainly by the rich, urban and affluent children in India. They are less susceptible to such infection than the crowded masses of poor children in India, who cannot afford the vaccine. It is a matter of giving protection to those who probably do not need it, and not giving the protection to those who need it because they cannot afford it.
Another new vaccine against Pneumococcus which was introduced in USA recently, is on the horizon and is just itching to get into the Indian market. There are several serotypes of Pnuemococcus causing disease in children and it is very expensive to make vaccine against all these serotypes. As the disease causing serotypes varies from place to place, it is almost impossible to manufacture vaccines which cover all the strains in all areas. So the present vaccine which protects against seven serotypes of Pneumococcus is a compromise between cost and effectiveness. These seven serotypes are the most common pathogens and protection against these seven offers protection against about 80% of infections in USA. Even inside USA the protection offered is different in various places as the serotypes differ in places. When it was introduced into South Africa, it was found that it was not of much use as the serotypes causing disease in South Africa are quite different from the ones present in the vaccine. This vaccine is going to be introduced into India without much knowledge about the kind of serotypes of Pnuemococcus prevalent in India. One study from CMC Vellore, suggested that the Pneumococcus prevalent in that area are quite different from the ones present in the vaccine. Still the vaccine may be introduced into the Indian market and with the strong publicity and advertisement by the drug company and by influencing the doctors that may find a place in the Indian immunization schedule.
In developed countries where most of the vaccines are developed and introduced first, even after the efficacy and safety of each vaccine has been proved, it undergoes a vigorous assessment regarding the cost versus benefit from routine administration of the vaccine. This takes into consideration many aspects of the vaccine: total cost of immunizing the target population, lives saved from its use, and cost savings from reduced hospital admissions and visit to the doctor. There are well known and proven methods to calculate this balance between cost of the vaccine and the health benefits and financial savings from the use of vaccines. As cost/benefit analysis of the newly introduced Rotavirus vaccine in the USA shows, even though the number of possible deaths prevented by the vaccine is only 13 for the whole of USA. But the main reason for using the vaccine in USA is the financial savings from reduced hospitalization and visit of the doctor. Similar analysis of the same vaccine will definitely show that even though it may have marginal health benefit, the financial cost will be against the use of the vaccine in India. It is the very high charges of hospitalization and visit to the doctor which makes the vaccine cost effective in USA. Since those costs are much less in India, any prudent analysis will show that the vaccine is not suitable for Indian conditions. But these considerations are never given a serious thought and study when a new vaccine is introduced in India. Many of the newer vaccines introduced in India, if analyzed rigorously will probably be shown not to be cost effective under Indian conditions. As the science of political economy is about the most prudent and useful allocation of restricted resources, any new vaccine being introduced to this country should undergo such analysis before its widespread use is encouraged.
Dr.Alexander Mathew, F.A.A.P (Diplomate American Board of Pediatrics) Chief of Pediatrics Lisie Hospital, Kochi.Kerala India, 682018
Competing interests: None declared
Competing interests: No competing interests
We are dismayed that the article ‘Rethinking global access to vaccines’ has been published as an ‘Analysis’ article in the BMJ (1). The article has the hallmarks and specious logic of a story planted by the vaccine industry and we hope that in fairness to developing countries, you will provide comparable space to present the counter point and dispute the implications of the paper.
HPV vaccine:
The authors write, “Our difficulty in disseminating well established vaccines cast doubts on our ability to promote wide spread use of new ones such as for diarrhea associated with rotavirus infection and for human papillomavirus (HPV). Currently - -93% of 260,000 annual deaths from cervical cancer occur outside the 60 wealthiest countries”
For a start, we would like to put these figures in its perspective. For the analysis let us assume that Gardasil, the vaccine against HPV related cervical cancer, covers all strains causing the cancer. (Actually Gardasil protects against 4 of the over-100 different strains of HPV and it protects against 70% of the strains presently associated with cervical cancer. It is not known if the infective strains will shift with time, with widespread use of the vaccine.) What will it cost to buy vaccines to avoid these 260,000 deaths? 21 million girls will have to be vaccinated each year, as they approach the age of 10 (2). The vaccine costs $400 per person. The total cost will be $8400 million. This program has to be sustained for over 20 years. Even if it prevents all cervical cancers, this would result in a mere 2% reduction of the mortality related to infective diseases. (The total deaths due to infective diseases is 10.9 million (2))
Let us assume that through very innovative pricing mechanisms, the cost of the vaccine comes down to $1 per dose. It will still cost $63 million for the vaccine alone, without including the cost of implementing the program and for injecting all these children.
Rotavirus vaccine:
The case for Gardasil has always been a little insecure because cervical cancers are not so common and the vaccine is exorbitantly expensive. Let us therefore examine the case for rotavirus vaccine – the other vaccine that the authors discuss in their introductory paragraph.
The authors lament the fact that it causes 440,000 deaths each year. Let us assume that we have a vaccine that covers all the human strains (A CDC sponsored study by Ramani and Kang has shown bovine-human strain reassortment and emergence of several new strains (not covered by vaccines) in India (3)). 126 million children around 2 months of age will need to be vaccinated three times (378 million doses) (2). At the present public sector cost of $7/dose (4) the cost of the vaccine will be $7938 million. This expenditure will bring down the deaths due to infections by 4%.
Vaccines and Market Forces:
Clearly, vaccines are not invariably a public good. We need to lay to rest, the concept that immunizations are always cost-effective (5). In an ideal market with perfect information, if a vaccine is not cost-effective and not capable of yielding better returns than other uses of the resource (6), there will be no demand for that vaccine. The compulsion to increase demand for these vaccines is felt by the manufacturers not the consumer. That is why organizations like GAVI have to enter the picture and give grants-in-aid to poor countries to offload those vaccines. It is hoped that poor countries can be persuaded to continue to use the vaccine after the aid is withdrawn. Willy-nilly poor nations are lured into a debt trap by such schemes. All the time, these organizations (like GAVI) masquerade as philanthropic organizations.
Drug trials among vulnerable populations:
Traditionally vaccines are tested by multinational manufacturers in the USA and Europe and only later in developing countries, as supplies and competition increase, and the cost of vaccine come down. This is in accordance with the Helsinki Declaration that trials be done in populations who are directly to use the drug.
Vaccine manufacturers want the rules changed. Chokshi and Kesselheim point out that Gardasil (the vaccine that costs over $400 for three doses needed to immunize one person) produced in the USA and Australia was tested in Brazil, India and Costa Rica (1). The cost of research is halved by conducting it in developing countries (7). The compensation needed to pay for adverse events is much lower. In an upside down world where profits are paramount, the authors write that this arrangement ‘could help meet international demand for low cost products’ (1). The fates of human guinea pigs in developing countries don’t count for much.
‘Competing interests: None declared’:
A casual reader of the article will notice it is written by a medical student and his teacher. However the BMJ demands to know more than just the names of the authors and it is published in small print. The article was written as the result of a ‘dialogue’ with the former President of Merck Vaccines (1,8) and a few others. To some of us, that explains a lot.
Email: puliyel@gmail.com
References
1. Chokshi DA, Kesselheim AS. Rethinking global access to vaccines BMJ 2008;336:750-3
2. WHO Revised global burden of disease 2002 estimates http://www.who.int/healthinfo/bodgbd2002revised/en/index.html accessed on 8/4/08
3. Ramani S, Kang G. Burden of disease of group A rotavirus infection in India. Indian J of Med Res 2007;125:619-32
4. PATH Rotavirus. http://www.rotavirusvaccine.org/documents/RotaQA_Jan06.pdf accessed 8/4/07.
5. Jean-Pierre Le Clavez. GAVI funding and assessment of vaccine cost -effectiveness. Lancet 2007;369:189.
6. Dhanasiri SK, Puliyel JM. Regulating vaccines: Can health- economics tools be used profitably? Indian Pediatrics 2007;44:11-14
7. Sharma D. India pressed to relax rules on clinical trials. Lancet 2004;363:1528-9.
8. Global HIV Vaccine Enterprise. Adel Mahmoud http://www.hivvaccineenterprise.org/_dwn/news/mahmoud_bio.pdf accessed 8/4/08
Competing interests: None, except that we live in a developing country – India.
Competing interests: No competing interests
Dear Sir,
The paper,[1] is a thought provoking one and raises issues that need further debate. The vaccine push has incapacitated the ability of the poor and the developing countries to think in terms of their own requirements, priorities and the needs to acquire capacities for producing vaccines well beyond a point when the developed countries think them to be obsolete. Instead they are forced to have vaccines the thinkers in the west would say as cost effective given their population.
The Vaccine Push is spearheaded by GAVI and WHO and surprisingly these organizations are forgetting to make available essential vaccines to the underdeveloped and developing countries and foster a co-operation amongst them in producing basic vaccines.
India is still struggling to immunize its children against six vaccine preventable diseases. In some states of India like in Bihar’s Kishanganj district the routine immunization is only 8.5%[2] and in Gonda district of Jharkhand it is 10.4%2.
In India there are more than 50% districts (321/593) where the vaccine coverage for six vaccine preventable diseases is less than 50% and the routine immunization has shown a declining trend over the years, some citing the reason as fatigue of the health worker in specific and the system in general due to repeated Pulse Polio Vaccine rounds and also polio putting a drain on the already strained health budgets as now promised funding for it has stopped and the third world countries are being asked to bear the burnt of polio eradication though the idea and the ultimate cost-benefit is for the rich countries for eradication of the polio. Now India would be spending around $44 Million on polio eradication this year while the routine immunization would get only around $14 Million.
So while the paper advocates access to vaccines like Hepatitis-b and Hib, we are concerned about the access to essential cost-effective vaccines in India so the disease burden due to conventional vaccine preventable diseases (Tetanus, tuberculosis, diphtheria, pertusis, measles) is reduced before we move towards the latest vaccines.(Table:1)[3]. Newer vaccines are being foisted on poor countries in an effort to reduce the cost of the vaccines in the West, therefore helping the developed countries themselves rather than helping the poor countries!
I agree with the contention of the authors that “ local logistic hurdles must be overcome to achieve equitable access”, but the question is how can the logistic hurdles be removed without putting up a “Functional Vaccine Delivery Mechanism” in place. In the absence of such a mechanism where we are unable to deliver essential routine vaccines, how can we think of introducing other vaccines when we would not be able to make them reach to the intended and so called poor!
Here lies the trick of pentavalent vaccine that makes it more costly putting a drain on already strained health systems of third world countries. Regarding the cost effective analysis as per the table number 20.6 of the book[4] the cost of pentavalent vaccines for Asia comes out to be $15.24 per person vaccinated and it is only $11.58 per person vaccinated for all the vaccines as for as the traditional EPI is concerned. The old EPI costs about $1 in India (not USA prices) for all the vaccines.
The newer GMP mechanism put by WHO have already forced the stoppage of production of essential vaccines in India[5] giving another blow to self sufficiency and creating dependence on private manufacturers as the anti-snake venom and vaccines like yellow fever, DPT,BCG and Measles are now out of stocks in many states of the country!.
So the priorities need to be seen as the ground reality in the respective countries and not in the contest of making vaccines cheaper by producing in bulk or giving assurances to the vaccine producers of using the vaccine in bulk irrespective of the need for it by the countries where they are intended to be put to use.
The vaccine manufacturers are keen for getting assurances for their supplies but are reluctant to compensate the damage by their product, this double talk need to be corrected and the poor need not be taken for guaranteed.
We strongly agree that we need to develop a mechanism whereas where relaxation in TRIPS is given to enable global distribution of vaccines as almost all trial of vaccine efficacy are done in Third world countries. This would be a just and fair trade as the trial countries are feeling alienated for not getting the benefits and are given meager compensation for the trials. Also the suggestion to build local capacity to scale up vaccine programmes and scale up production needs a serious thought.
In India many people are dying with snake bites (Table-1), but nobody is advocating for the easy availability of anti-snake venom but all the talk is only of introducing Hepatitis-b and pentavalent vaccines!
So the argument by the authors for “wider global availability” needs thinking in the context of the ground situation in the respective countries and not the availability of vaccines in developed countries.
Table-1. The cases and deaths3 due to vaccine/ antisera /antitoxin preventable diseases, India, 2006 Condition/Disease Cases Deaths Snake Bite 55490 1086 Japanese Encephalitis (J.E.) 2832 658 Typhoid 726484 651 Tetanus (other than neonatal) 2803 365 Rabies 361 361 Measles 63515 99 Neonatal Tetanus 620 80 Diphtheria 2745 66 Pertusis 23935 17 Polio 116 1
REFERENCES:-
[1] Choaski DA, Kesselheim AS. Thinking global access to Vaccines, BMJ 336;2008;750-753
[2]. International Institute for Population Sciences, Mumbai. District Level Household Survey on Reproductive and Child Health DLHS-RCH, INDIA, 2002-04: http://www.rchindia.org/sr_india.htm [2007, April 7]
[3] National Health Profile, India – 2006. Central Bureau of Health Intelligence, Dte.General of Health Services, Ministry of Health & Family Welfare, Govt. of India.2006
[4] Logan Brenzel, Lara J. Wolfson, Julia Fox-Rushby, Mark Miller, and Neal A. Halsey. Vaccine-Preventable Diseases in Breman JG, Jamison D T (Ed) Disease Control Priorities in Developing Countries. The World Bank 2006 (2nd Ed). Oxford University Press 165 Madison Avenue New York NY 10016: 389-412.
[5] Ramachandran R. Vaccine worries. Frontline. Apr. 11, 2008 25( 07): http://www.frontlineonnet.com/stories/20080411250700400.htm
Competing interests: None declared
Competing interests: No competing interests
Re: Rethinking global access to vaccines
First, in response to substantive points made in several posts, we wish to emphasize a fundamental premise in our paper. Rigorous research on the safety and efficacy of vaccines -- as well as methods of vaccine distribution that augment existing health infrastructure -- is context- dependent, in India and elsewhere. Local circumstances must be taken into account for such research to have value for patients in developing countries. We hope our analysis helps inspire public health authorities to continue working to ensure that safe vaccines are developed and then made available to patients in resource-poor settings.
Second, in reply to the personal attacks in some of the previous posts, we reiterate the clear statements in our article that we have no conflicts of interest to disclose and that any opinions expressed are our own. Academic discussions with colleagues are a well-established part of scholarship and should not be chilled. Therefore, we welcome further debate on the controversial issues we sought to address, but baseless accusations do not effectively serve that discourse.
Competing interests: None declared
Competing interests: No competing interests