1. Research group in Global health: Ethics, economics and culture Is it fair to favour the sickest HIV patients when there is ART scarcity? Kjell Arne Johansson (MD, PhD fellow), Neema Sofaer, Lydia Kapiriri, Erasmus Otolok-Tanga, Lynn Atuyambe, Ole Frithjof Norheim University of Bergen kjell.johansson@isf.uib.no

2. Research group in Global health: Ethics, economics and culture Plan 1.Objective 2.Background 3.Methods 4.Impartial ethical analysis

3. Research group in Global health: Ethics, economics and culture Building bridges: - Roughly? - Exact measures?

4. Research group in Global health: Ethics, economics and culture Objective To analyse and evaluate the practice of giving priority to the sickest Is the priority to patients with lowest CD4 count, when those with higher CD4 counts could benefit more from it, fair?

5. Research group in Global health: Ethics, economics and culture Background Worldwide, 33.4 million people live with HIV and only 4 million people are receiving ART The 2009 WHO ART guidance recommends provision of ART to each HIV patient whose CD4 count is less than 350 cells/µl 42% out of all HIV patients (=14 million) are considered potential beneficiaries from ART Need-coverage gap: 14-4 million

6. Research group in Global health: Ethics, economics and culture Priority setting strategies used Priority setting avoidance: No concrete guidance on whom to choose in favour of others Limit setting left to the individual clinician and a first-come, first- served selection Arbitrary barriers to ART determine who receives ART The sickest HIV patients were explicitly favoured by a majority of health professional that were responsible for initiating ART at two hospitals in Uganda [ref Sofaer et al. and Kapiriri et al.] Evidence from HIV clinics show that ART is frequently started too late according to medical indications, meaning that the sickest patients are favoured in ART provision (a median CD4 count of 108 cells/µl at initiation of ART)

7. Research group in Global health: Ethics, economics and culture Methods Impartial case analysis: –A systematic method for analysis of ethical dilemmas in eight steps –Facilititates illumination of all morally relevant concerns Solving multiprincipled conflicts: –Equity-efficiency trade-offs

8. Research group in Global health: Ethics, economics and culture 1.What is the problem? What are the alternative choices? 2.What is the evidence concerning the outcomes of the different alternatives? 3.Are there guidelines or legal acts that regulate the issue at hand? If yes, are they acceptable? 4.Who are the affected parties? 5.What are the benefits and burdens for the affected parties under the alternative options? 6.Are substantial interests (such as a legitimate interest in health outcomes) in conflict? 7.Are fundamental principles in conflict? 8.Multi-principled conflicts: How to adjudicate between conflicting principles identified in 7?

9. Research group in Global health: Ethics, economics and culture 1) What is the problem? What are the alternative choices? Is it fair to allocate ART preferentially to patients whose CD4 count is low (very sick) when, as a result, others with higher CD4 counts (not so sick) who could benefit more from ART cannot receive it?

10. Research group in Global health: Ethics, economics and culture 1) What is the problem? What are the alternative choices? Can be illustrated by two cases: Two-person case: You can only treat one out of two HIV patients. Both persons are 30 years old, where the only difference between them is that one has a CD4 count below 200 cells/µl and the other CD4 counts between 200-350 cells/µl. Population level case: In further ART roll-out, is it fair to give ART to all patients with CD4 counts below 200 cells/µl or a proportion of patients with CD4 counts between 200 and 350 cells/µl?

11. Research group in Global health: Ethics, economics and culture 2) What is the evidence concerning the outcomes of the different alternatives? Johansson et al., AIDS Research and Therapy. 2010;7(3). Few health economic evaluations available – and those that are available only have a health system perspective

12. Research group in Global health: Ethics, economics and culture Two-person case outcome Mean LE: 42.4 Mean LE: 38.4

13. Research group in Global health: Ethics, economics and culture Population case outcome

14. Mean LE: 7.6*100% = 7.6 Mean LE 14.5*52%= 7.6 25 34.8 49.3 42.4 34.8 25 LE no ART LE early start to only a proportion LE no ART LE late start to all Reasonable disagreement

15. Mean LE increase: 7.6*100% = 7.6 Mean LE increase: 14.5*60%=8.7 25 34.8 49.3 42.4 34.8 25 LE no ART LE early start to only a proportion LE no ART LE late start to all

16. Research group in Global health: Ethics, economics and culture 3) Are there guidelines or legal acts that regulate the issue at hand? If yes, are they acceptable? WHO guidelines (2009): ART recommended for all patients with CD4 counts below 350 cells/µl This revision has not yet been adopted in many low income countries - at least not in Ugandan, Ethiopian and Tanzanian guidelines Legal acts, including international human rights treaties, do not mention whether or not ART allocation should be given preferentially to the sickest

17. 4) Who are the affected parties? 1.Patients denied or not offered ART and their families 2.Patients offered ART and their families 3.Health professionals involved in selecting patients for ART. 4.Funding organisations (including local and national health authorities) 5.Patients with conditions other than HIV, who need other health care services, including public health measures* 6.Citizens (in need of non-health services)* * = 5 and 6 not included in the analysis since we only consider whom to provide ART and not how much ART to supply

18. Research group in Global health: Ethics, economics and culture 5) What are the benefits and burdens for the affected parties under the alternative options? Benefits: Patients offered ART gain on average 7.6 or 14.5 years of life. More patients will benefit from ART with early start –Their families, employers and society will benefit accordingly Burdens: Those not offered ART will forego the expected life years they would gain from ART –Their families, employers and society will be burdened accordingly

19. Research group in Global health: Ethics, economics and culture 5) Continued… Providers: Late start: Satisfaction of seeing many very ill patients achieve rapid and dramatic gains in health-related quality of life and, frequently, life-expectancy Funding organisations: Late-start: potential to save more people and gain higher ART coverage rates since patients are on ART for shorter periods

20. Research group in Global health: Ethics, economics and culture 6) Are substantial interests (such as a legitimate interest in health outcomes) in conflict? All patients who need ART have an interest in increasing their life-expectancy and health-related quality of life. Such interests are substantial; they can not easily be dismissed. When there is insufficient ART for all, these interests conflict.

21. Research group in Global health: Ethics, economics and culture 7) Fundamental principles in conflict? Two person case: Principled ethical conflict between maximizing benefits and equal distribution in life expectancy. How much weight to maximization (6.9 life years gained in expected individual utility) versus to equal distribution in outcomes (priority to worst off)?

22. Research group in Global health: Ethics, economics and culture 7) Fundamental principles in conflict? Population-level case: A) Principled ethical conflict between giving many patients a high chance to receive a lower benefit or few patients a large benefit (fair-chances vs best-outcomes) B) Maximization (increase in total expected utility if ART coverage is >52% for those with early start) and equal distribution Willing to give up improved total mean LE of 1.1 years for the sake of full equality? –How much weight to fair-chances to many persons (equality) versus maximizing individual outcomes for few persons (inequality)?

23. Research group in Global health: Ethics, economics and culture 8) Multi-principled conflicts: How to adjudicate between conflicting principles identified in 7? We have no principled way of deciding which principle should have the greater weight In distributive conflicts, a combination of a maximizing and egalitarian principle is also possible. A consequence-sensitive approach to distributive fairness must define the appropriate trade-off between equity/fairness concerns and maximizing concerns.

24. Research group in Global health: Ethics, economics and culture Achievement index n: total number of people μ: average health in this population hi: health for group i Ri: relative rank of the ith group (rank 1 is the rank of the best-off) v: inequality aversion (1 = no preference for equality) Anand S. The concern for equity in health. J Epidemiol Community Health 2002;56:485-7

25. Research group in Global health: Ethics, economics and culture Inequality aversion (v) ART to person with best expected benefit (CD4 200-350 cells/µl) ART to very sick person (CD4 <200 cells/µl) Achievement index Two-person case trade-off

26. Research group in Global health: Ethics, economics and culture Population case trade-off

27. ART coverage (%) Early start (CD4 200-350 cells/µl) Late start (CD4 <200 cells/µl) Health equity preferences (v=2) Achievement index Health maximization preferences (v=1) ∆AI = 2.2 ∆AI = 3.0 ∆AI =3.3 ∆AI = 1.6 Population case trade-off

28. Research group in Global health: Ethics, economics and culture Conclusion Wether we consider it fair to give priority to patients with lowest CD4 count, when those with higher CD4 counts could benefit more from it, depends on our inequality aversion. On a population level, we need a modest preference for equal distribution (v>1.4) in order to favour ART initiation at CD4 <200