Transcript Slide 1

Occupy
Medicine
99%
1%
Vaccines for
versus
profits for the
Jacob M. Puliyel
St Stephens Hospital, Delhi
[email protected]
Raffle of a dead
donkey
Cost
500 tickets @ $2
each
Refund
Profit
$ 100
$ 1000
$2
$ 898
250,000 death in India each year due to
Hepatitis B
Miller et al Health Economics 2000;9:19-35
ICMR data suggests about 5000 die
Dhir et al Ind J of Gastroenterol 1998;17:100-3
Model Used
Model ‘stratified by income group and
geographic region’ was used and it was
available on the CDC web site:
http://nihfic.cit.nih.gov/research
No model on web site
Model using data from
Taiwan Males
25% Male hepatitis B carriers die in Taiwan
World Record
300% of mortality in Taiwanese female carriers
Beasley Cancer 1988;61:1942-56
It is 17 times higher than mortality in Canadian
carriers
Villeneuve et al Gastroenterology 1994:106:1000-5
Extrapolation
Taiwan Male Mortality
4% population are carriers in India
If 1 in 4 carriers die of the disease
1% of deaths in India must be due to
Hepatitis B
1% of deaths among India’s 1 billion
population is 250,000!
Puliyel JM. Lancet 2004;363:659
Health Economics publishes call for
retraction of paper
Model used by Miller must be published or the
paper retracted
Puliyel JM Health Economics 2004;13:1147
Miller has replied that the model was lost
Miller MA Health Economics 2004;13:1147-8
The paper has NOT been retracted yet
Invasive H. Influenza B (Hib)
disease
Incidence of invasive disease with Hib is very
low.
Incidence:
9/100,000
109/100,000
Asia
Western Pacific
Levine Pediatr Infect Dis J 1998;17:S95-113
Is Hib really needed in Asia?
Editorial in Bulletin of WHO
Lau YL Bulletin WHO 1999;77:867-8
Natural Immunity in Asia
1. High antibody levels pre-vaccination at 6
weeks
2. Not passive immunity
Without immunization: Increasing antibody titers
with increasing age
Tastan Ind Pediatr 2000;37:414-7
Natural Immunity in Asia: Vaccine
Booster Effect
3. After vaccination, antibody levels increase ten
times higher than normal suggesting that child
was immune before vaccination
Acharya Ind Pediatr 1997;34:9-15
Kumar Ind J Pediatr 1997;64:839-47
Natural Immunity to Hib
Animal model: E coli cross-reactive antigens
against Hib
Schneerson Inf and Immunol 1971;4:397-401
Bradshaw Lancet 1971;1095-98
Petrie Br J Exp Path 1971;13:380-94
Infection with organisms like E Coli may
protect Asians against Hib
Puliyel Vaccine 2001;19:4592-4
Inappropriate-Media
Hypothesis for Low Culture Rate
Chocolate agar supplemented with
Isovitalex
Gellert Lancet. 1994 ;344:959
Invasive Bacterial Infection
Surveillance Group (IBIS) Study
•
•
•
•
Continuous surveillance for 4 years
6 of the largest hospitals in 6 cities
Appropriate culture techniques
Findings: 125 cases in 4 years!
Small numbers?
Access to the hospital is perhaps a problem
Solution: Community studies needed.
IBIS Group Clinical Infect. Dis 2002;34:949-57
WHO Prospective Community Study
Hib Meningitis
Incidence Hib meningitis 7/100,000
(Levine had estimated 9/100,000 invasive disease)
Low rate of Hib in children in this region:
(a) genetic factors
(b) early exposure to bacteria with cross-reacting
antigens
(c) low bacterial virulence
Minz et al IJMR 2008;128:57-64
New Ideas
Low Incidence of Hib
• Culture media not the problem:
IBIS Study
• Access to hospital not the issue:
Mitz Community Study
Perhaps prior antibiotic use problem
Probe study for areas with
Low Culture Rate
Probe studies to identify reduction in
clinical disease after immunization
No culture proof needed
The Hib initiative.
www.hibaction.org/research.php#vaccine_probe.
Indonesia Lambok Study
55000 children:
• Double blind
• Hamlet randomized
• Active case surveillance
Gessner Lancet 2005;365:43-52
Vaccine Effectiveness
(Vaccine preventable Hib disease)
Disease
manifestation
Vaccine
Effectiveness
(Incidence
Unvaccinated –
Vaccinated)
Alveolar
Consolidation/
Effusion
- 43
(95% CI -185 to 98
Bangladesh Probe 2007
• Not randomized. No blinding
• Incident case-control study
• Population 68,000
• 35% received Hib vaccine
• 475 Pneumonia.
Baqui Ped Infect Dis 2007;26:565-71
Bangladesh Probe
Vaccine Effectiveness - 3 doses
Baqui Ped Infect Dis 2007;26:565-71
Disease
Community Controls
(matched for age , sex, season
and distance from hospital)
Meningitis
40%
(95% CI -138 to 85)
Pneumonia
(WHO protocol)
20%
(95% CI -10 to 43)
Press release
WHO Dhaka , 28 June 2007
New study shows Hib vaccine protects children
from significant burden of life-threatening
pneumonia and meningitis
Press release signed by WHO, GAVI, USAID, Johns
Hopkins
Puliyel Demanding Accountability. BMJ 2010; c4081
Puliyel Eu tu WHO. IJMR 2010;131:588-9
No Hidden Agenda
• Cost of Hib in the USA is $5.60 (1998 prices)
• Price can come down only if Hib is part of EPI
internationally
Nossal Nature Medicine 1988;5:475-6
Steinhoff Lancet 1993 ;342:630-1
Poor countries must use the vaccine so the price of
the vaccine in the West can come down
Puliyel Vaccine 2001;19:4592-4
Hib eliminated:
Replacement by other invasive strains of H.
influenza
Proportional increase in non-B H. influenza strains,
including non-serotypeable strains, causing invasive H
influenza disease in the post-Hib vaccine era in Canada
Tsang et al Clin Infect Dis. 2007;44:1611-4.
Brown et al Clin Infect Dis 2009;49:1240–1243
Pneumococcal vaccine
Cost
Rs 12,000 per child
Benefit
Reduce 3.6 cases of pneumonia /1000
children vaccinated
Madhi WHO Bull 2008;86
Pneumococcal Vaccine Harm: Risk of
Asthma Doubled
1.4 additional cases of Asthma for every 3.6 cases
pneumonia avoided (per 1000 children vaccinated)
Klugman K. NEJM 2003;349:1341-8
Spending Rs 12 million
to save Rs 40
• Vaccine costs Rs 12,000 per child
• Vaccinating 1000 children costs Rs 12 million
• Treating 4 cases of pneumonia will cost Rs 40 if
WHO recommended Septran is used
Dabade Lancet 2009;373:2195-6
If prices come down to Rs 1200/child
you will spend Rs 1.2 million to save Rs 40
Cure is Worse than Disease
Strain Replacement
Invasive pneumococcal infections increased
after PCV 7
Serotype 19A isolated, one third of which
were resistant to multiple antibiotics.
Kaplan Pediatrics 2010;125: 429-436
Rota Virus in India
• Continuous reassortment of bovine and
human strains.
Ramani S. IJMR 2007;125:619-32
• No study on reduction in diarrhoea
among vaccinated in India
Community Perspective:
Allocative Efficiency
Hypothetical Case Study
1. Rota virus control costs Rs 200 crores
Saves 1 life year per Rs 20,000
2. Polio control costs Rs 350 crores
Saves 1 life year per Rs 10,000
3. TB control costs Rs 700 crores
Saves 1 life year per Rs 5000
Rank Incremental Cost-Utility Ratios
Budgetary Constraint: Rs 1000 crores
1. TB control costs Rs 700 crores
Saves 1 life per Rs 5000
2. Polio control costs Rs 350 crores
Saves 1 life per Rs 10,000
3. Rota virus control costs Rs 200 crores
Saves 1 life per Rs 20,000
50% of the population don’t receive
the basic
EPI vaccines costing Rs 30
• HPV
Rs 9000/child
• Rotavirus
Rs 2000/child
• Pneumococcal vaccine Rs 12000/child
Community Perspective
Newer vaccines: Are they ethical?
Pneumococcal Vaccine:
Perspective of the Individual
Exorbitantly expensive
Cost per child Rs 12,000
MRP includes incentive to doctor Rs 3000
• Very small benefits (3.6/1000 pneumonia)
• Individual risks - Asthma (1.4/1000)
• Community risks - Antibiotic Resistant Strains
Can it be prescribed ethically to rich?
Half Truths and Lies
• 10.6 million children under five years of age die
each year
• Pneumonia, leading cause of mortality among
children in developing countries
SAGE WHO
www.who.int/immunization/SAGE_wg_detailedreview_pneumo
Vaccine.pdf
Pneumonia is a vaccine preventable disease
The Unsaid Truth
• Vaccine is against only one bacterial
pathogen 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
Pneumococcal vaccine protection against
vaccine-strain invasive-disease (VS-IPD) 80%
(CI 58% to 90%, P < 0.0001)
Cochrane meta analysis . Lucero 2009
The other half of the truth
No reduction in all-cause mortality
[OR 11% (95% CI -1% to 21%, P = 0.08)]
Incidence of vaccine strain invasive disease was
so low - the absolute risk difference (ARR) is only 0.002 (CI: -0.004 to -0.000)
Number Needed to Prevent One Case 500.
Puliyel Microbiology and Infection 2011
Misleading Statistics
• Risk reduction (RR) of 50% sounds good for a
vaccine
Patients and doctors are easily convinced
Suppose Risk comes down from 4% to 2%
• RR is 50%
• It affords 2% reduction in absolute risk.
Unlikely to convince patients to take the treatment
Morgan Clinical Oncology 2004;16:549e560
Yellow fever
• 100% Protection
• ARR
ZERO
(As disease non-existent India)
RR and ARR
Die
Live
Total
RR = R2/R1 = (0.0001/0.0002) =
50%
Control
2
998
1000
ARR = R1 – R2 =
0.0002 - 0.0001 = 0.0001
Vaccine
1
999
1000
Total
3
1997
2000
NNT = 1/ARR = 1/0.0001 = 1000
Efficacy as 'absolute risk reduction' to
calculate cost benefits easily
• Impressive sounding reductions in relative risk
can mask much smaller reductions in absolute
risk.
• Clinical decisions based on absolute risk (AR)
rather than relative risk (RR).
Godlee F 2008. Absolute risk please. BMJ
How to avoid buying a dead
donkey
What the MSF can
do
Resolution for WHA:
Intervention to enhance child
survival
Efficacy must ALWAYS be reported in
terms of 'absolute risk reduction'
NOT Relative risk (RR)
so that Member States can calculate cost
benefits easily