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Pertussis post-exposure prophylaxis among household contacts: a cost-utility analysis.

Thampi N, Gurol-Urganci I, Crowcroft NS, Sander B - PLoS ONE (2015)

Bottom Line: Newer macrolides offer fewer side effects at higher drug costs.Associated health outcomes and costs were compared, and incremental cost-effectiveness ratios (ICER) were calculated in 2012 Canadian dollars.While results were sensitive to changes in PEP effectiveness (11% to 87%), disease transmission (variable among age groups) and hospitalization costs ($379 to $59,644), the choice of strategy remained unchanged.

View Article: PubMed Central - PubMed

Affiliation: Division of Infectious Diseases, Children's Hospital of Eastern Ontario, Ottawa, ON, Canada; University of Ottawa, Ottawa, ON, Canada.

ABSTRACT

Background: Recent pertussis outbreaks have prompted re-examination of post-exposure prophylaxis (PEP) strategies, when immunization is not immediately protective. Chemoprophylaxis is recommended to household contacts; however there are concerns of clinical failure and significant adverse events, especially with erythromycin among infants who have the highest disease burden. Newer macrolides offer fewer side effects at higher drug costs. We sought to determine the cost-effectiveness of PEP strategies from the health care payer perspective.

Methods: A Markov model was constructed to examine 4 mutually exclusive strategies: erythromycin, azithromycin, clarithromycin, or no intervention, stratified by age group of contacts ("infant", "child", and "adult"). Transition probabilities, costs and quality-adjusted life years (QALYs) were derived from the literature. Chronic neurologic sequelae were modeled over a lifetime, with costs and QALYs discounted at 5%. Associated health outcomes and costs were compared, and incremental cost-effectiveness ratios (ICER) were calculated in 2012 Canadian dollars. Deterministic and probabilistic sensitivity analyses were performed to evaluate the degree of uncertainty in the results.

Findings: Azithromycin offered the highest QALYs in all scenarios. While this was the dominant strategy among infants, it produced an ICER of $16,963 per QALY among children and $2,415 per QALY among adults. Total QALYs with azithromycin were 19.7 for a 5-kg infant, 19.4 for a 10-year-old child, and 18.8 for a 30-year-old adult. The costs of azithromycin PEP among infants, children and adults were $1,976, $132 and $90, respectively. While results were sensitive to changes in PEP effectiveness (11% to 87%), disease transmission (variable among age groups) and hospitalization costs ($379 to $59,644), the choice of strategy remained unchanged.

Interpretation: Pertussis PEP is a cost-effective strategy compared with no intervention and plays an important role in contact management, potentially in outbreak situations. From a healthcare payer perspective, azithromycin is the optimal strategy among all contact groups.

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Related in: MedlinePlus

Tornado diagram of the univariate sensitivity analysis for the azithromycin PEP strategy for child (A) and adult (B) contacts.Azithromycin remained the dominant strategy among infants. The bars represent the variation in cost-effectiveness ratios from the base case scenario in response to sequential changes in model parameters, with the vertical axis reflecting the base case ICER. The maximal and minimal values were tested according to ranges outlined in Table 1. (A) Axis at $16,963 per QALY. (C) Axis at $2,415 per QALY.
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pone.0119271.g002: Tornado diagram of the univariate sensitivity analysis for the azithromycin PEP strategy for child (A) and adult (B) contacts.Azithromycin remained the dominant strategy among infants. The bars represent the variation in cost-effectiveness ratios from the base case scenario in response to sequential changes in model parameters, with the vertical axis reflecting the base case ICER. The maximal and minimal values were tested according to ranges outlined in Table 1. (A) Axis at $16,963 per QALY. (C) Axis at $2,415 per QALY.

Mentions: The lifetime expected health outcomes for a previously healthy 10-year-old contact were 19.38 QALYs without intervention and increased by 12 days (0.032 QALYs) with azithromycin PEP, with a $97 cost increase for an ICER of $16,963 per QALY when compared with clarithromycin. While clarithromycin was less expensive than azithromycin, there were fewer QALYs gained, thus making it the non-preferred option in the base case scenario and sensitivity analyses. In the probabilistic sensitivity analysis, the median ICER of azithromycin compared to clarithromycin was $16,709 per QALY (mean $16,966 per QALY, 95% CI: $16,900-$16,972 per QALY), and was sensitive to the probability of a GI adverse event with clarithromycin and azithromycin, the probability of acquiring disease, and PEP effectiveness, but not sensitive to the complications and costs of pertussis, including probability and cost of hospitalization, the probability and costs of encephalitis and its sequelae, probability of death, and changes in utility on PEP or with any pertussis health state (Fig. 2A). No PEP had a 95% probability of being cost-effective when the willingness-to-pay threshold was below $2,000 per QALY, whereas azithromycin had a 95% probability of being cost-effective at the threshold of $50,000 per QALY (Fig. 3A).


Pertussis post-exposure prophylaxis among household contacts: a cost-utility analysis.

Thampi N, Gurol-Urganci I, Crowcroft NS, Sander B - PLoS ONE (2015)

Tornado diagram of the univariate sensitivity analysis for the azithromycin PEP strategy for child (A) and adult (B) contacts.Azithromycin remained the dominant strategy among infants. The bars represent the variation in cost-effectiveness ratios from the base case scenario in response to sequential changes in model parameters, with the vertical axis reflecting the base case ICER. The maximal and minimal values were tested according to ranges outlined in Table 1. (A) Axis at $16,963 per QALY. (C) Axis at $2,415 per QALY.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4352053&req=5

pone.0119271.g002: Tornado diagram of the univariate sensitivity analysis for the azithromycin PEP strategy for child (A) and adult (B) contacts.Azithromycin remained the dominant strategy among infants. The bars represent the variation in cost-effectiveness ratios from the base case scenario in response to sequential changes in model parameters, with the vertical axis reflecting the base case ICER. The maximal and minimal values were tested according to ranges outlined in Table 1. (A) Axis at $16,963 per QALY. (C) Axis at $2,415 per QALY.
Mentions: The lifetime expected health outcomes for a previously healthy 10-year-old contact were 19.38 QALYs without intervention and increased by 12 days (0.032 QALYs) with azithromycin PEP, with a $97 cost increase for an ICER of $16,963 per QALY when compared with clarithromycin. While clarithromycin was less expensive than azithromycin, there were fewer QALYs gained, thus making it the non-preferred option in the base case scenario and sensitivity analyses. In the probabilistic sensitivity analysis, the median ICER of azithromycin compared to clarithromycin was $16,709 per QALY (mean $16,966 per QALY, 95% CI: $16,900-$16,972 per QALY), and was sensitive to the probability of a GI adverse event with clarithromycin and azithromycin, the probability of acquiring disease, and PEP effectiveness, but not sensitive to the complications and costs of pertussis, including probability and cost of hospitalization, the probability and costs of encephalitis and its sequelae, probability of death, and changes in utility on PEP or with any pertussis health state (Fig. 2A). No PEP had a 95% probability of being cost-effective when the willingness-to-pay threshold was below $2,000 per QALY, whereas azithromycin had a 95% probability of being cost-effective at the threshold of $50,000 per QALY (Fig. 3A).

Bottom Line: Newer macrolides offer fewer side effects at higher drug costs.Associated health outcomes and costs were compared, and incremental cost-effectiveness ratios (ICER) were calculated in 2012 Canadian dollars.While results were sensitive to changes in PEP effectiveness (11% to 87%), disease transmission (variable among age groups) and hospitalization costs ($379 to $59,644), the choice of strategy remained unchanged.

View Article: PubMed Central - PubMed

Affiliation: Division of Infectious Diseases, Children's Hospital of Eastern Ontario, Ottawa, ON, Canada; University of Ottawa, Ottawa, ON, Canada.

ABSTRACT

Background: Recent pertussis outbreaks have prompted re-examination of post-exposure prophylaxis (PEP) strategies, when immunization is not immediately protective. Chemoprophylaxis is recommended to household contacts; however there are concerns of clinical failure and significant adverse events, especially with erythromycin among infants who have the highest disease burden. Newer macrolides offer fewer side effects at higher drug costs. We sought to determine the cost-effectiveness of PEP strategies from the health care payer perspective.

Methods: A Markov model was constructed to examine 4 mutually exclusive strategies: erythromycin, azithromycin, clarithromycin, or no intervention, stratified by age group of contacts ("infant", "child", and "adult"). Transition probabilities, costs and quality-adjusted life years (QALYs) were derived from the literature. Chronic neurologic sequelae were modeled over a lifetime, with costs and QALYs discounted at 5%. Associated health outcomes and costs were compared, and incremental cost-effectiveness ratios (ICER) were calculated in 2012 Canadian dollars. Deterministic and probabilistic sensitivity analyses were performed to evaluate the degree of uncertainty in the results.

Findings: Azithromycin offered the highest QALYs in all scenarios. While this was the dominant strategy among infants, it produced an ICER of $16,963 per QALY among children and $2,415 per QALY among adults. Total QALYs with azithromycin were 19.7 for a 5-kg infant, 19.4 for a 10-year-old child, and 18.8 for a 30-year-old adult. The costs of azithromycin PEP among infants, children and adults were $1,976, $132 and $90, respectively. While results were sensitive to changes in PEP effectiveness (11% to 87%), disease transmission (variable among age groups) and hospitalization costs ($379 to $59,644), the choice of strategy remained unchanged.

Interpretation: Pertussis PEP is a cost-effective strategy compared with no intervention and plays an important role in contact management, potentially in outbreak situations. From a healthcare payer perspective, azithromycin is the optimal strategy among all contact groups.

Show MeSH
Related in: MedlinePlus