TO THE EDITOR—The analysis by Schneider and colleagues [1] raises two concerns— one methodological, one clinical—that undermine the policy conclusions of the article. A basic tenet of economic evaluation holds that mutually exclusive strategies should be compared based on their marginal contribution—not their absolute contribution—to both costs and benefits [2, 3]. Yet, the paper presents costeffectiveness ratios that evaluate every strategy using the status quo as the basis of comparison. This error leads to a serious misinterpretation of findings, as noted in Table 1. The corrected version highlights a critical finding that is not apparent in the original: Many strategies are dominated (ie, they cost more and deliver fewer
Note Potential conflicts of interest. All authors: No reported conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.
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Misinterpretation of HIV Preexposure Prophylaxis Findings
benefits than 1 or more other strategies) and should therefore be eliminated from consideration. Indeed, there are only 4 nondominated strategies for which it is appropriate to report cost-effectiveness ratios. This mistake carries over to Figure 2 in Schneider et al’s article. Although points on the figure are correctly arrayed, the 3 dark lines emanating from the origin (labeled “ICER Threshold”) have no interpretable meaning. Here again, the error lies in comparing everything to the status quo. By convention [2, 3], the figure should instead highlight the efficient frontier (ie, the convex envelope defined by the nondominated interventions); this outer boundary denotes the greatest possible quality-adjusted life-years that can be obtained for any given investment level. The correct interpretation of the output from the authors’ model is that preexposure prophylaxis (PrEP) meets Australian standards of cost-effectiveness only when targeted to the uninfected members of regular, serodiscordant partnerships (strategies 10 and 11). Closer examination of the modeling assumptions for these 2 strategies reveals the second concern—that the analysis does not appear to account for the potential of antiretroviral therapy (ART) to offset the benefits of PrEP in serodiscordant partnerships. Both Australian and international guidelines strongly recommend offering ART to human immunodeficiency virus (HIV)–infected partners in serodiscordant couples to reduce HIV transmission to uninfected partners [4, 5]. Concomitant ART will dramatically reduce the impact and the costeffectiveness of targeting PrEP to the uninfected partner.
Table 1. Original and Corrected Versions of Schneider et al’s Table 1
Total Costs (Discounted)
Scenario
Incremental Costs (Discounted)
QALYs (Discounted)
QALYs Gained (Discounted)
Incremental Costeffectiveness (Discounted)
Cost-effectiveness results, as they appear in Schneider et al [1] Status quo (no PrEP)
1
10% of MSM start PrEP
$1 133 834 739
$817 951 923 $315 882 816
488 557
487 952 605
$521 848
2
20% of MSM start PrEP
$1 448 968 232
$631 016 309
489 429
1477
$427 149
3
30% of MSM start PrEP
$1 770 146 281
$952 194 358
490 094
2142
$444 559
4
15% of MSM with >10 partners per 6 mo start PrEP
$984 003 011
$166 051 088
488 874
922
$180 146
5
15% of MSM with >20 partners per 6 mo start PrEP
$946 049 221
$128 097 298
488 830
878
$145 960
6
15% of MSM with >50 partners per 6 mo start PrEP
$848 568 951
$30 617 028
488 180
228
$134 185
7
30% of MSM with >10 partners per 6 mo start PrEP
$1 149 063 799
$331 111 876
489 455
1503
$220 252
8
30% of MSM with >20 partners per 6 mo start PrEP
$1 073 427 953
$255 476 030
489 347
1395
$183 195
9
30% of MSM with >50 partners per 6 mo start PrEP
$882 823 962
$64 872 039
488 523
571
$113 673
10
15% of HIV-negative men in discordant regular partnerships start PrEP
$822 374 587
$4 422 664
488 479
527
$8399
11
30% of HIV-negative men in discordant regular partnerships start PrEP
$830 301 331
$12 349 408
489 019
1067
$11 575
Cost-effectiveness results, recomputed and presented in conformity with widely accepted guidelines for economic evaluationc 0
Status quo (no PrEP)
$817 951 923
10
15% of HIV-negative men in discordant regular partnerships start PrEP
$822 374 587
$4 422 664
488 479
487 952 527
$8392
11
30% of HIV-negative men in discordant regular partnerships start PrEP
$830 301 331
$7 926 744
489 019
540
$14 679
6
15% of MSM with >50 partners per 6 mo start PrEP
$848 568 951
$18 267 620
488 180
(839)
Dominateda
9
30% of MSM with >50 partners per 6 mo start PrEP
$882 823 962
$34 255 011
488 523
343
Dominateda
5
15% of MSM with >20 partners per 6 mo start PrEP
$946 049 221
$63 255 259
488 830
307
Dominateda
4
15% of MSM with >10 partners per 6 mo start PrEP
$984 003 011
$37 953 790
488 874
44
Dominateda
8
30% of MSM with >20 partners per 6 mo start PrEP
$1 073 427 953
$89 424 942
489 347
473
dominatedb
1
10% of MSM start PrEP
$1 133 834 739
$60 406 786
488 557
(790)
Dominatedb
7
30% of MSM with >10 partners per 6 mo start PrEP
$1 149 063 799
$15 229 060
489 455
898
$731 107
2
20% of MSM start PrEP
$1 448 968 232
$299 904 433
489 429
(26)
Dominateda
3
30% of MSM start PrEP
$1 770 146 281
$321 178 049
490 094
665
$971 960
Abbreviations: HIV, human immunodeficiency virus; MSM, men who have sex with men; PrEP, preexposure prophylaxis; QALY, quality-adjusted life year. a
Strong dominance.
b
Weak dominance: program 8 costs more and delivers less than the combination of programs 7 and 11.
c
See references [2, 3].
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A. David Paltiel,1 Rochelle P. Walensky,2 and Kenneth A. Freedberg2 1
Yale School of Public Health, Yale School of Management, New Haven, Connecticut; and 2 Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts
References
Downloaded from http://cid.oxfordjournals.org/ at Rutgers University Libraries/Technical Services on January 16, 2015
1. Schneider K, Gray RT, Wilson DP. A costeffectiveness analysis of HIV preexposure prophylaxis for men who have sex with men in Australia. Clin Infect Dis 2014; 58:1027–34. 2. Gold MR, Siegel JE, Russel LB, Weinstein MC. Cost-effectiveness in health and medicine. Report of the Panel on Cost-effectiveness in Health and Medicine. New York: Oxford University Press, 1996. 3. Drummond MF, Sculpher MJ, Torrance GW, O’Brien BJ, Stoddart GL. Methods for the economic evaluation of health care programs. 3rd ed. Oxford: Oxford University Press, 2005. 4. Australasian Society for HIV Medicine. 2013 antiretroviral guidelines with Australian commentary. Available at: http://arv.ashm.org.au/ pdf/when-to-start.pdf. Accessed 27 February 2014. 5. World Health Organization. Consolidated guidelines on the use of antiretroviral drugs for treating and preventing HIV infection: recommendations for a public health approach June 2013 ( p. 83). Available at: http:// apps.who.int/iris/bitstream/10665/85321/1/ 9789241505727_eng.pdf. Accessed 27 February 2014. Correspondence: A. D. Paltiel, PhD, Yale School of Public Health, 60 College St, New Haven, CT 06520-8034 (david. [email protected]). Clinical Infectious Diseases 2014;59(1):139–41 © The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals. [email protected]. DOI: 10.1093/cid/ciu240
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Note Potential conflicts of interest. All authors: No reported conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.
CORRESPONDENCE
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Misinterpretation of HIV Preexposure Prophylaxis Findings
benefits than 1 or more other strategies) and should therefore be eliminated from consideration. Indeed, there are only 4 nondominated strategies for which it is appropriate to report cost-effectiveness ratios. This mistake carries over to Figure 2 in Schneider et al’s article. Although points on the figure are correctly arrayed, the 3 dark lines emanating from the origin (labeled “ICER Threshold”) have no interpretable meaning. Here again, the error lies in comparing everything to the status quo. By convention [2, 3], the figure should instead highlight the efficient frontier (ie, the convex envelope defined by the nondominated interventions); this outer boundary denotes the greatest possible quality-adjusted life-years that can be obtained for any given investment level. The correct interpretation of the output from the authors’ model is that preexposure prophylaxis (PrEP) meets Australian standards of cost-effectiveness only when targeted to the uninfected members of regular, serodiscordant partnerships (strategies 10 and 11). Closer examination of the modeling assumptions for these 2 strategies reveals the second concern—that the analysis does not appear to account for the potential of antiretroviral therapy (ART) to offset the benefits of PrEP in serodiscordant partnerships. Both Australian and international guidelines strongly recommend offering ART to human immunodeficiency virus (HIV)–infected partners in serodiscordant couples to reduce HIV transmission to uninfected partners [4, 5]. Concomitant ART will dramatically reduce the impact and the costeffectiveness of targeting PrEP to the uninfected partner.
Table 1. Original and Corrected Versions of Schneider et al’s Table 1
Total Costs (Discounted)
Scenario
Incremental Costs (Discounted)
QALYs (Discounted)
QALYs Gained (Discounted)
Incremental Costeffectiveness (Discounted)
Cost-effectiveness results, as they appear in Schneider et al [1] Status quo (no PrEP)
1
10% of MSM start PrEP
$1 133 834 739
$817 951 923 $315 882 816
488 557
487 952 605
$521 848
2
20% of MSM start PrEP
$1 448 968 232
$631 016 309
489 429
1477
$427 149
3
30% of MSM start PrEP
$1 770 146 281
$952 194 358
490 094
2142
$444 559
4
15% of MSM with >10 partners per 6 mo start PrEP
$984 003 011
$166 051 088
488 874
922
$180 146
5
15% of MSM with >20 partners per 6 mo start PrEP
$946 049 221
$128 097 298
488 830
878
$145 960
6
15% of MSM with >50 partners per 6 mo start PrEP
$848 568 951
$30 617 028
488 180
228
$134 185
7
30% of MSM with >10 partners per 6 mo start PrEP
$1 149 063 799
$331 111 876
489 455
1503
$220 252
8
30% of MSM with >20 partners per 6 mo start PrEP
$1 073 427 953
$255 476 030
489 347
1395
$183 195
9
30% of MSM with >50 partners per 6 mo start PrEP
$882 823 962
$64 872 039
488 523
571
$113 673
10
15% of HIV-negative men in discordant regular partnerships start PrEP
$822 374 587
$4 422 664
488 479
527
$8399
11
30% of HIV-negative men in discordant regular partnerships start PrEP
$830 301 331
$12 349 408
489 019
1067
$11 575
Cost-effectiveness results, recomputed and presented in conformity with widely accepted guidelines for economic evaluationc 0
Status quo (no PrEP)
$817 951 923
10
15% of HIV-negative men in discordant regular partnerships start PrEP
$822 374 587
$4 422 664
488 479
487 952 527
$8392
11
30% of HIV-negative men in discordant regular partnerships start PrEP
$830 301 331
$7 926 744
489 019
540
$14 679
6
15% of MSM with >50 partners per 6 mo start PrEP
$848 568 951
$18 267 620
488 180
(839)
Dominateda
9
30% of MSM with >50 partners per 6 mo start PrEP
$882 823 962
$34 255 011
488 523
343
Dominateda
5
15% of MSM with >20 partners per 6 mo start PrEP
$946 049 221
$63 255 259
488 830
307
Dominateda
4
15% of MSM with >10 partners per 6 mo start PrEP
$984 003 011
$37 953 790
488 874
44
Dominateda
8
30% of MSM with >20 partners per 6 mo start PrEP
$1 073 427 953
$89 424 942
489 347
473
dominatedb
1
10% of MSM start PrEP
$1 133 834 739
$60 406 786
488 557
(790)
Dominatedb
7
30% of MSM with >10 partners per 6 mo start PrEP
$1 149 063 799
$15 229 060
489 455
898
$731 107
2
20% of MSM start PrEP
$1 448 968 232
$299 904 433
489 429
(26)
Dominateda
3
30% of MSM start PrEP
$1 770 146 281
$321 178 049
490 094
665
$971 960
Abbreviations: HIV, human immunodeficiency virus; MSM, men who have sex with men; PrEP, preexposure prophylaxis; QALY, quality-adjusted life year. a
Strong dominance.
b
Weak dominance: program 8 costs more and delivers less than the combination of programs 7 and 11.
c
See references [2, 3].
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0
A. David Paltiel,1 Rochelle P. Walensky,2 and Kenneth A. Freedberg2 1
Yale School of Public Health, Yale School of Management, New Haven, Connecticut; and 2 Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts
References
Downloaded from http://cid.oxfordjournals.org/ at Rutgers University Libraries/Technical Services on January 16, 2015
1. Schneider K, Gray RT, Wilson DP. A costeffectiveness analysis of HIV preexposure prophylaxis for men who have sex with men in Australia. Clin Infect Dis 2014; 58:1027–34. 2. Gold MR, Siegel JE, Russel LB, Weinstein MC. Cost-effectiveness in health and medicine. Report of the Panel on Cost-effectiveness in Health and Medicine. New York: Oxford University Press, 1996. 3. Drummond MF, Sculpher MJ, Torrance GW, O’Brien BJ, Stoddart GL. Methods for the economic evaluation of health care programs. 3rd ed. Oxford: Oxford University Press, 2005. 4. Australasian Society for HIV Medicine. 2013 antiretroviral guidelines with Australian commentary. Available at: http://arv.ashm.org.au/ pdf/when-to-start.pdf. Accessed 27 February 2014. 5. World Health Organization. Consolidated guidelines on the use of antiretroviral drugs for treating and preventing HIV infection: recommendations for a public health approach June 2013 ( p. 83). Available at: http:// apps.who.int/iris/bitstream/10665/85321/1/ 9789241505727_eng.pdf. Accessed 27 February 2014. Correspondence: A. D. Paltiel, PhD, Yale School of Public Health, 60 College St, New Haven, CT 06520-8034 (david. [email protected]). Clinical Infectious Diseases 2014;59(1):139–41 © The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals. [email protected]. DOI: 10.1093/cid/ciu240
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