A Risk-Characterization Framework for Decision-Making at the Food and Drug Administration (2011) / Chapter Skim
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3 Case Study of a Mitigation-Selection Decision
3 Case Study of a Mitigation-Selection Decision
Pages 46-65
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From page 46... ...
FRAMING THE ISSUE: VACCINE WITHDRAWAL Before vaccine availability, the burden of rotavirus infection in the United States was estimated to be 3.5 million cases per year in children less than 5 years old (Murphy et al.
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. Considerable discussion followed the withdrawal of the RRV-TV vaccine and the implications 1 Severe rotavirus gastroenteritis is defined as diarrhea with or without vomiting that requires hospitalization or rehydration in a medical facility; stool-sample analysis confirms rotavirus infection (other than vaccine strain)
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From page 48... ...
to develop estimates of the human-health consequences of the two options. Although data were available, as indicated in the detailed development of the estimates below, characterizing the public-health consequences of the two decision options required the committee to make informed judgments, some assumptions, and a variety of calculations.
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From page 49... ...
from vaccine-induced intussusception Morbidity Number experiencing severe adverse 18,300 (5,800-44,200) total: 55,000 (23,000-110,000)
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from post-vaccine fever or diarrhea Personal For vaccine-induced adverse effects Parents of 80-90% of vaccine-eligible Not applicable controllability children have the ability to avoid or reduce the risks to their child For rotavirus disease Not controllable Not controllable Ability to Ability of informed institution to Adverse effects would have to occur at a Not applicable detect adverse detect population-level effects rate at least 5 times higher than normally health effects associated with product being expected to be detected; very-long-latency evaluated adverse effects are unlikely to be detected Ability to Probability that an informed For RRV-TV induced effects: Not applicable mitigate adverse institution will be able to reduce or >99% health effects mitigate adverse health effects associated with the product being evaluated if such a problem is known to exist
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From page 51... ...
Because RRV-TV was not on the market for very long before it was withdrawn, the committee did not think it was appropriate to use the vaccination rates associated with it to calculate the vaccination rates that would have been accomplished by a fully mature program. Instead, data on overall vaccination rates in the United States for vaccines available at that time were reviewed.
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From page 52... ...
As noted above, estimating the rates required informed judgments to be made about the relevant data and their applicability to the future vaccination rates with RRVTV. Vaccination rate and vaccine effectiveness, with the sizes of the birth cohort and the exposed population, are sufficient to develop estimates of the exposed populations of interest: those exposed to the risk of vaccine-associated side effects and those exposed to the risks of rotavirus disease.
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From page 53... ...
No. not unprotected Vaccine protected under 5 years old effectiveness annually % vaccinated 38% 80% 2,784,000 13,920,000 38% 90% 2,632,000 13,160,000 38% 100% 2,480,000 12,400,000 75% 80% 1,600,000 8,000,000 75% 90% 1,300,000 6,500,000 75% 100% 1,000,000 5,000,000 95% 80% 960,000 4,800,000 95% 90% 580,000 2,900,000 95% 100% 200,000 1,000,000 FIGURE 3-1 Estimating the size of the unprotected population given uncertainty in vaccination rates and vaccine effectiveness.
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1997) and generally did not require additional physician or emergency-department visits, the committee characterized them as adverse health consequences that affect only quality of life, similar to those cases of symptomatic rotavirus disease that do not require medical intervention.
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Number of children Susceptible populationa 20,000,000 2,800,000c 3,500,000b 4,000,000d Total cases Deathsb 20 30 40 Severe adverse health effectsb 23,000 55,000 110,000 365,000e 500,000b 672,000e Less severe adverse health effects Adverse health effects 2,944,970 affecting only quality of lifef Rates among susceptible children Deaths 0.000001 0.0000015 0.000002 Severe adverse health effects 0.00115 0.00275 0.0055 Less severe adverse health 0.018 0.025 0.034 effects Adverse health effects 0.147 affecting only quality of life a Uncertainty in the number of children under 5 years old is insignificant relative to other uncertainties, so only a best estimate is used. b Based on Glass et al.
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From page 56... ...
For purposes of this case study, the committee assumed that all occurrences of intussusceptions led to hospitalization (severe adverse health effects) , and thus the rate of severe adverse effects of RRVTV was assumed to be the same as the rate of vaccine-induced intussusception.
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From page 57... ...
To estimate the numbers of deaths and severe adverse health effects attributable to vaccination, the committee used the rates of intussusception after RRV-TV and the mortality rate from intussusception described above and applied them to the size of the vaccinated population. The number of deaths for this decision option was estimated as follows: Nf = Rf + If (Eq.
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From page 58... ...
Simply substituting the rates of severe adverse health effects and less severe adverse health effects for the mortality rates in Equations 3-1b and 3-1c yields estimates of the total number of children who would experience those effects if the vaccine were retained (see example calculation in Table 3-3)
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From page 59... ...
of susceptible children 6,500,000 Rotavirus infection and rate of adverse effects in the susceptible populationa Rotavirus infection rate 17.5% Mortality rate 0.00015% Severe-disease rate 0.28% Less-severe-disease rate 2.5% Rate of only quality-of-life effects 14.7% No. of deaths 9.8 No.
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From page 60... ...
Although the vast majority of parents choose to have their children vaccinated with recommended vaccines, the committee estimates that 80-90% of parents understand that they have the right to decline vaccinations and to control the RRV-TV-induced risks if they so desire. In the absence of the vaccine, the ability of parents to prevent their child from contracting rotavirus disease is virtually zero.
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From page 61... ...
If such effects arose with RRV-TV on the market and the effects were serious (ones that led to death or severe adverse health effects) and occurred at a rate substantially higher than would be expected for this population, the reporting systems in place at that time would have identified those effects quickly.
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USING THE RISK CHARACTERIZATION TO SUPPORT DECISION-MAKING Table 3-1 highlights the differences in public-health consequences that could be expected if the vaccine is withdrawn or left on the market. If the vaccine remained on the market, the number of children who would suffer adverse health effects -- ranging from diarrhea to death -- from rotavirus and RRV-TV would be substantially less than the number who would suffer similar effects of rotavirus disease if the vaccine were removed from the market.
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From page 63... ...
. The decision-making step remains complicated by additional factors, as discussed above, but the use of this framework will enable FDA to compare the public-health consequences of multiple mitigation approaches on a common basis and to describe the consequences with a common language.
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From page 64... ...
1997. Randomised placebo controlled trial of rhesus-human reassortant rotavirus vaccine for prevention of severe rotavirus gastroenteritis.
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From page 65... ...
2003a. Reappraisal of the association of intussusception with the li censed live rotavirus vaccine challenged initial conclusions.
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