Cash interventions to improve clinical outcomes for pulmonary tuberculosis: systematic review and meta-analysis

Bull World Health Organ 2018;96:471–483 | doi: http://dx.doi.org/10.2471/BLT.18.208959 Systematic reviews 471 Cash interventions to improve clinical outcomes for pulmonary tuberculosis: systematic review and meta-analysis Aaron Richterman,a Jonathan Steer-Massaro,b Jana Jarolimova,c Liem Binh Luong Nguyen,d Jennifer Werdenberge & Louise C Iversf Introduction Tuberculosis remains one of the top 10 causes of death worldwide, with the highest burden of disease in low- and middle-income countries.1 In these countries, the disease disproportionately affects the most vulnerable populations.1,2 In 2015, the World Health Organization’s (WHO’s) End TB Strategy set the goal of a 90% reduction in tuberculosis deaths, an 80% reduction in tuberculosis incidence rate and zero catastrophic costs for tuberculosis-affected families by 2030.3 These goals explicitly acknowledge the need to both directly treat people infected with the disease and address so- cial determinants of health to improve tuberculosis outcomes. Social protection policies protect individuals or house- holds during periods when they are unable to financially support themselves because of a range of conditions, such as illness or disability.4 Cash transfer interventions, defined as cash payments provided to selected beneficiaries by formal institutions, are one form of social protection that has been proposed in the setting of tuberculosis.5,6 Such interventions can either be tuberculosis-specific or tuberculosis-sensitive.6 Tuberculosis-specific interventions target directly tuberculosis patients and their households, and are typically incorpo- rated into existing tuberculosis treatment programmes.6 A tuberculosis-sensitive intervention is part of a broader social protection scheme, potentially affecting tuberculosis outcomes by targeting communities and groups that are at high risk for tuberculosis. The effect on health outcomes, cost–effectiveness and feasibility of these two strategies are not well established and likely to vary based on the local social protection and health-care infrastructure. Since a review in 2011 on the effects of cash transfer interventions on tuberculosis outcomes in low- and middle- income countries was inconclusive,7 we assessed the cur- rent state of the evidence for such interventions. We were especially interested if cash transfer to people receiving treatment for active pulmonary tuberculosis affects their clinical outcomes. Methods We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines.8 The review protocol is available from the corresponding author. To identify studies on the use of cash transfer interven- tions during the treatment of active pulmonary tuberculosis in low- and middle-income countries, we searched the on- line databases PubMed®, Embase®, Cochrane Library and ClinicalTrials.gov. We used the search string “Tuberculosis” AND (“financial support” OR “token economy” OR “re- imbursement” OR “economic burden” OR “incentives” OR “cash transfer” OR “enablers”) to identify studies published Objective To assess cash transfer interventions for improving treatment outcomes of active pulmonary tuberculosis in low- and middle- income countries. Methods We searched PubMed®, Embase®, Cochrane Library and ClinicalTrials.gov for studies published until 4 August 2017 that reported on cash transfer interventions during the treatment of active pulmonary tuberculosis in low- and middle-income countries. Our primary outcome was a positive clinical outcome, defined as treatment success, treatment completion or microbiologic cure. Using the purchasing power parity conversion factor, we converted the amount of cash received per patient within each study into international dollars (Int$). We calculated odds ratio (OR) for the primary outcome using a random effects meta-analysis. Findings Eight studies met eligibility criteria for review inclusion. Seven studies assessed a tuberculosis-specific intervention, with average amount of cash ranging from Int$ 193–858. One study assessed a tuberculosis-sensitive intervention, with average amount of Int$ 101. Four studies included non-cash co-interventions. All studies showed better primary outcome for the intervention group than the control group. After excluding three studies with high risk of bias, patients receiving tuberculosis-specific cash transfer were more likely to have a positive clinical outcome than patients in the control groups (OR: 1.77; 95% confidence interval: 1.57–2.01). Conclusion The evidence available suggests that patients in low- and middle-income countries receiving cash during treatment for active pulmonary tuberculosis are more likely to have a positive clinical outcome. These findings support the incorporation of cash transfer interventions into social protection schemes within tuberculosis treatment programmes. a Department of Medicine, Brigham and Women’s Hospital, 75 Francis Street, Boston, MA 02115, United States of America (USA). b Department of Obstetrics and Gynecology, Boston University School of Medicine, Boston, USA. c Department of Medicine, Massachusetts General Hospital, Boston, USA. d Infection, Antimicrobials, Modelling and Evolution, Unité Mixte de Recherche 1137, INSERM, Paris, France. e Department of Pediatrics, Dell Children’s Hospital, Austin, USA. f Center for Global Health, Massachusetts General Hospital, Boston, USA. Correspondence to Aaron Richterman (email: arichterman@partners.org). (Submitted: 24 January 2018 – Revised version received: 26 April 2018 – Accepted: 30 April 2018 – Published online: 4 June 2018 ) Systematic revi w Bull World Health Organ 2018;96:471–483| doi: http://dx.doi.org/10.2471/BLT.18.208959472 Systematic reviews Cash interventions to improve tuberculosis outcomes Aaron Richterman et al. between the databases’ inceptions and 4 August 2017. We also manually reviewed reference lists of identified systematic reviews, relevant articles and abstracts from the Union World Conference on Lung Health 2011–2016. Eligibility criteria We considered clinical trials and observa- tional studies published in English, Span- ish or French that assessed cash transfer interventions directed at people initiating treatment for microbiologically confirmed or clinically suspected active pulmonary tuberculosis. We used the WHO defini- tion for tuberculosis and the 2017 World Bank’s classification of low- and middle- income countries.9,10 We included studies that reported standard outcomes of treat- ment completion, microbiologic cure or treatment success, which includes both treatment completion and cure.10 Study selection and data collection After removing duplicate records, two reviewers independently screened titles and abstracts of all records for inclusion in full-text review. After screening, two different reviewers independently applied eligibility criteria to each full-text article. Two reviewers then proceeded to data ex- traction using a standardized form created for the study (Box 1). Disagreements were settled by consensus among all authors. To better understand the relative amount of cash distributed in the in- cluded studies, we converted the average and maximum possible amount of cash received per patient within each study into international dollars (Int$) using the purchasing power parity conversion factor, and then adjusted for inflation into 2016 Int$ with the local infla- tion conversion factor.11 If the average amount of cash received by patients in the intervention group was not reported in the article, we contacted the authors to provide the figures. Because tuberculosis dispropor- tionately affects the poorest households within a given context,12 we estimated the average amount of cash received per patient as a proportion of annual individual income by dividing the aver- age amount of cash received per patient by the median income per capita of the lowest quintile of that country from the time period of the study.11 Household- level income data were not available to estimate the interventions as proportion of annual household income. Assessment of bias For the randomized study, we assessed risk of bias using the Cochrane Collabo- ration Risk of Bias Tool, and defined a randomized study as overall high risk of bias if the trial met criteria for high risk of bias in more than one assessed domain.13 We assessed risk of bias within non-randomized studies using the Newcastle-Ottawa Scale, defining a non-randomized study as overall high risk of bias if it had zero stars in any of the three assessed categories.14 We generated a funnel plot to evaluate Box 1. Type of data extracted from identified studies on cash interventions to improve tuberculosis outcome We extracted data on location; urban and rural setting; time frame; study design; number of subjects; age and gender of participants; HIV prevalence; number with microbiologically confirmed tuberculosis; number with confirmed or suspected MDR and XDR tuberculosis; type of usual care for tuberculosis; annual individual or household income; whether the intervention was conditional; tuberculosis-specific or sensitive intervention; concurrently implemented co- interventions; primary and secondary outcomes. HIV: human immunodeficiency virus; MDR: multidrug resistant; XRT: extensively-drug resistant. Fig. 1. Flowchart showing the selection of studies on cash interventions to improve tuberculosis clinical outcomes, 1991–2017 1528 records identified through database search 1210 from PubMed® 65 from Embase® 46 from The Cochrane Library 7 from ClinicalTrials.gov 9 additional records identified through review of references 1 study of a tuberculosis-sensitive intervention 4 studies of tuberculosis-specific interventions (included in meta-analysis) 1537 total identified records 639 duplicates removed 798 records excluded 92 full-text articles excluded • 40 were an ineligible study type • 5 focused on latent or MDR/XDR tuberculosis • 9 concerned food incentives • 4 concerned incentives to providers only • 7 did not concern cash intervention during treatment • 13 had no relevant outcome • 3 had no comparator group • 8 were in a high income country • 2 evaluated the same population as another study • 1 was not in English, Spanish or French 898 titles and abstracts screened 100 full-text articles assessed for eligibility 8 studies included in qualitative synthesis3 studies had high overall risk of bias Bull World Health Organ 2018;96:471–483| doi: http://dx.doi.org/10.2471/BLT.18.208959 473 Systematic reviews Cash interventions to improve tuberculosis outcomesAaron Richterman et al. Ta bl e 1. De sig n, se tt in g an d po pu la tio n of in clu de d st ud ie s i n th e sy st em at ic re vi ew o n ca sh in te rv en tio ns to im pr ov e tu be rc ul os is cli ni ca l o ut co m es , 1 99 1– 20 17 Au th or , p ub lic at io n ye ar Ye ar o f s tu dy St ud y d es ig n an d se tt in g Us ua l c ar e % m al e % sm ea r po sit iv e % H IV % M DR tu be rc ul os is In te rv en tio n gr ou p Co nt ro l g ro up Tu be rc ul os is -s pe ci fic in te rv en ti on s Fa rm er e t a l.,1 7 1 99 1 19 89 –1 99 0 Cl us te r n on -r an do m ize d in te rv en tio n st ud y in a cl in ic in ru ra l H ai ti Fr ee c ar e, n o co m m un ity h ea lth w or ke rs o r D O TS 33 10 0 5 N R Pe op le w ith n ew ly d ia gn os ed tu be rc ul os is fro m se ct or ad ja ce nt to c lin ic Pe op le w ith n ew ly d ia gn os ed tu be rc ul os is fro m o ut sid e se ct or ad ja ce nt to c lin ic Ch iri co e t a l.,2 0 2 01 1 20 04 –2 00 8 Re tro sp ec tiv e co ho rt in o ne h ea lth d ist ric t o f Bu en os A ire s, Ar ge nt in a 51 % o f p at ie nt s re ce iv in g D O TS , c os t o f ca re N R 57 N R 6 0. 91 Al l p eo pl e w ith n ew ly di ag no se d tu be rc ul os is re po rt ed to n at io na l tu be rc ul os is co nt ro l pr og ra m m e Pe op le w ith n ew ly d ia gn os ed tu be rc ul os is w ho d id n ot g et th e in te rv en tio n be ca us e de em ed no t t o ha ve th e fin an ci al n ee d, ch os en a t r an do m a m on g al l pe op le w ho d id n ot g et th e in te rv en tio n Ro ch a et a l.,2 1 2 01 1 20 07 –2 01 0 Co ho rt w ith h ist or ic al co nt ro l i n ei gh t sh an ty to w ns in L im a, Pe ru D O TS , f re e ca re N R N R N R N R Pe op le w ith n ew ly di ag no se d tu be rc ul os is fro m ho us eh ol ds in th e na tio na l tu be rc ul os is pr og ra m m e w he re in te rv en tio n ha d be en im pl em en te d Pe op le w ith n ew ly d ia gn os ed tu be rc ul os is fro m h ou se ho ld s in th e na tio na l t ub er cu lo sis pr og ra m m e w he re th e in te rv en tio n ha d no t y et b ee n im pl em en te d Ci ob an u et a l.,1 8 2 01 4 20 08 , 2 01 1 N at io n- w id e re tro sp ec tiv e co ho rt w ith h ist or ic al c on tro l in th e Re pu bl ic o f M ol do va D O TS , c os t o f c ar e N R 69 36 3 0 Ad ul ts w ith d ru g- su sc ep tib le tu be rc ul os is re gi st er ed fo r tre at m en t i n 20 11 (a fte r in tro du ct io n of in ce nt iv es ) Ad ul ts w ith d ru g- su sc ep tib le tu be rc ul os is re gi st er ed fo r tre at m en t i n 20 08 (b ef or e in tro du ct io n of in ce nt iv es ) Lu e t a l.,1 9 2 01 5 20 06 –2 01 0 Re tro sp ec tiv e co ho rt in Sh an gh ai , C hi na D O TS , f re e ca re 63 10 0 N R 0 M ig ra nt s t re at ed fo r sm ea r- po sit iv e pu lm on ar y tu be rc ul os is liv in g in o ne o f th e ei gh t d ist ric ts p ro vi di ng ca sh M ig ra nt s t re at ed fo r s m ea r- po sit iv e pu lm on ar y tu be rc ul os is liv in g in o ne o f t he n in e di st ric ts no t p ro vi di ng c as h U kw aj a et a l.,1 6 2 01 7 20 14 Pr os pe ct iv e pr e- a nd po st - i nt er ve nt io n in a la rg e, ru ra l, s ec on da ry - ca re fa ci lit y in E bo ny i St at e, N ig er ia D O TS , c os t o f c ar e N R 54 55 15 0 Al l r eg ist er ed p eo pl e re ce iv in g fir st -li ne a nt i- tu be rc ul os is tre at m en t a t st ud y sit e du rin g 3- m on th pe rio d of in te rv en tio n Al l r eg ist er ed p eo pl e re ce iv in g fir st -li ne a nt i-t ub er cu lo sis tre at m en t a t s tu dy si te d ur in g 3- m on th p er io d w ith ou t fin an ci al p ac ka ge W in gfi el d et a l.,1 5 20 17 20 14 –2 01 5 Cl us te r r an do m ize d co nt ro l t ria l i n th irt y- tw o co nt ig uo us sh an ty to w ns in C al la o, Pe ru D O TS , f re e ca re 62 70 5 9 Pe op le st ar tin g tre at m en t f or tu be rc ul os is ad m in ist er ed by th e na tio na l t ub er cu lo sis pr og ra m m e, ra nd om ize d to re ce iv e th e so ci oe co no m ic su pp or t i nt er ve nt io n Pe op le st ar tin g tre at m en t f or tu be rc ul os is ad m in ist er ed by th e na tio na l t ub er cu lo sis pr og ra m m e, ra nd om ize d no t to re ce iv e th e so ci oe co no m ic su pp or t i nt er ve nt io n (c on tin ue s. . . ) Bull World Health Organ 2018;96:471–483| doi: http://dx.doi.org/10.2471/BLT.18.208959474 Systematic reviews Cash interventions to improve tuberculosis outcomes Aaron Richterman et al. publication bias for studies included in the meta-analysis. Data analysis All identified studies were included in a qualitative synthesis. After excluding studies at overall high risk of bias, we generated summary effect measures using a random effects model for our primary outcome of interest, the odds ratio (OR) of a positive clinical outcome, defined as either a treatment success; treatment completion, if a study did not report treatment success; or micro- biologic cure, if a study did not report treatment success or treatment comple- tion. If a study reported ORs adjusted for potential confounders we included these ratios in our analysis. We assessed heterogeneity by using the Cochran’s Q test and the I2 statistic. Among studies included in meta- analysis, we wanted to investigate sources of heterogeneity, including av- erage amount of cash transfer, presence of non-cash co-intervention, treatment success rate in the control group, urban or rural setting, human immunodefi- ciency (HIV) prevalence, multidrug resistance (MDR) or extensive-drug re- sistance (XDR) tuberculosis prevalence and World Bank income classification. However, there was not enough infor- mation available to complete a random effects meta-regression model using any of these variables. We used Comprehensive Meta- Analysis software version 3 (Biostat, Inc., Englewood, United States of America) and Review Manager Version 5.3 (The Cochrane Collaboration, Lon- don, United Kingdom of Great Britain and Northern Ireland) for data analysis. Results Study selection We identified 1537 publications and after removal of 639 duplicates, we screened 898 titles and abstracts yield- ing 100 full-text articles to be assessed for eligibility. Of these full-text articles, 92 were excluded (Fig. 1). We included eight eligible articles: one randomized control trial,15 two non-randomized intervention studies,16,17 and five obser- vational studies,18–22 comprising a total of 21 976 subjects. Study settings and populations Table 1 summarizes the settings and populations of the included studies. With the exception of one study that took place in 1989–1990,17 the studies assessed cash transfer interventions between 2004 and 2015. The settings varied: one study took place in a rural clinic,17 one in a large rural secondary- care facility,16 four in urban centres,15,19–21 and two were nation-wide studies.18,22 Three of the studies took place in coun- tries currently on the WHO list of high- burden countries for tuberculosis16,19,22,23 and two other studies were in a country currently considered high burden for MDR tuberculosis.15,21 One study focused on migrant work- ers, a high-risk group within an urban centre.19 The remaining studies evaluated all tuberculosis patients identified within a given geographic or clinical service area. The control groups were either pa- tients randomized to the non-interven- tion group,15 living in a non-intervention area,17,19 historical controls from the same population before the implementation of the intervention,16,18,21 eligible for the intervention, but not yet receiving cash, because of administrative delay,22 or not eligible for the intervention, because of insufficient financial need.20 Prevalence of HIV seropositiv- ity among the study populations was 0–15% in the six studies reporting the outcome.15,16.14,17,18,22 Patients with MDR/ XDR tuberculosis were excluded from four studies,16,18,19,22 two studies reported low prevalence (1–9%),15,20 while two did not report on drug susceptibility.17,21 Five studies reported free care for tu- berculosis,15,17,19,21,22 with the others not specifically commenting on the cost of care.16,18,20 Participants in six studies re- ceived the WHO recommended directly observed therapy, short-course.24 Tuberculosis-specific interventions In total, seven studies evaluated tuber- culosis-specific cash transfer interven- tions (Table 2).15–21 Six of these studies were at least partially conditional on clinic attendance or treatment comple- tion,15–20 and one did not report whether the intervention was conditional.21 Four studies described an additional trans- portation reimbursement.17–19,21 Four studies did not report the aver- age amount of cash received by patients in the intervention group. We contacted the authors of these studies and authors of two studies provided the amount,16,18 while this information was not avail- able for other studies.19,20 The average Au th or , p ub lic at io n ye ar Ye ar o f s tu dy St ud y d es ig n an d se tt in g Us ua l c ar e % m al e % sm ea r po sit iv e % H IV % M DR tu be rc ul os is In te rv en tio n gr ou p Co nt ro l g ro up Tu be rc ul os is -s en si ti ve in te rv en ti on s To rre ns e t a l.,2 2 2 01 6 20 10 N at io n- w id e re tro sp ec tiv e co ho rt in Br az il Fr ee d ia gn os tic s an d tre at m en t f or a ll pa tie nt s. Tu be rc ul os is pa tie nt s o nl y en ro lle d in to d ire ct ly o bs er ve d th er ap y if ju dg ed to be a bl e to c om pl et e tre at m en t 50 N R 7 0 Pe op le w ith n ew ly d ia gn os ed no n- M D R tu be rc ul os is re co rd ed in th e na tio na l da ta ba se w ho re ce iv ed c as h du rin g tre at m en t Pe op le w ith n ew ly d ia gn os ed no n- M D R tu be rc ul os is re co rd ed in th e na tio na l d at ab as e w ho w er e el ig ib le fo r c as h in te rv en tio ns , b ut o nl y st ar te d to re ce iv e th em a fte r t re at m en t du e to a dm in ist ra tiv e de la ys D OT S: d ire ct ly o bs er ve d th er ap y, sh or t c ou rs e; H IV : h um an im m un od efi ci en cy v iru s; M D R: m ul tid ru g re sis ta nt ; N R: n ot re po rte d. (. . . co nt in ue d) Aaron Richterman et al. Cash interventions to improve tuberculosis outcomes Systematic reviews 475Bull World Health Organ 2018;96:471–483| doi: http://dx.doi.org/10.2471/BLT.18.208959 Ta bl e 2. Ty pe o f c as h tr an sf er in te rv en tio n of in clu de d st ud ie s i n th e sy st em at ic re vi ew o n ca sh in te rv en tio ns to im pr ov e tu be rc ul os is cli ni ca l o ut co m es , 1 99 1– 20 17 Au th or , y ea r Ca sh tr an sf er in te rv en tio n Co nd iti on al in te rv en tio n; m et ho d of ca sh d el iv er y M ax im um ca sh , I nt $a Av er ag e ca sh , I nt $a Av er ag e ca sh a s pe rc en t o f a nn ua l in co m eb Ad di tio na l i nt er ve nt io ns c Tu be rc ul os is -s pe ci fic in te rv en ti on s Fa rm er e t a l.,1 7 1 99 1 M on th ly c as h tra ns fe r a nd tr av el re im bu rs em en t M ix ed : t ra ve l r ei m bu rs em en t co nd iti on al o n cl in ic a tte nd an ce , m on th ly tr an sf er n ot c on di tio na l, be ca us e cl in ic st aff w ou ld c om e to th e ho m es o f t he p at ie nt s m iss in g cl in ic v isi ts ; c as h 90 0 90 0 17 3 D ai ly v isi ts b y co m m un ity h ea lth w or ke r d ur in g fir st m on th . F oo d su pp le m en ts fo r fi rs t 3 m on th s. If th e pa tie nt d id n ot a tte nd th e ap po in tm en t, so m eo ne fr om th e cl in ic w en t t o th e ho us eh ol d to in ve st ig at e Ch iri co e t a l.,2 0 2 01 1 M on th ly c as h du rin g pe rio d of tre at m en t e qu al to lo w c iv il se rv ic e sa la ry . Fo r p at ie nt s n ot o th er w ise pr ot ec te d by o th er so ci al sa fe ty n et be ne fit s Ye s: cl in ic v isi ts ; c as h de liv er ed by th e ba nk e m pl oy ee a fte r t he pa tie nt p re se nt ed d oc um en ta tio n of p ro gr am m e en ro lm en t N A N A N A N on e Ro ch a et a l.,2 1 2 01 1 Ca sh tr an sf er s f or tr an sp or ta tio n, po ve rt y re du ct io n, a nd o th er tu be rc ul os is- as so ci at ed c os ts N R N A 29 1 17 (5 .5 )d M ic ro cr ed it lo an s, vo ca tio na l tra in in g, m ic ro en te rp ris e ac tiv iti es (e .g . r ai sin g an im al s, ho m e- ba se d m an uf ac tu rin g) , f oo d tra ns fe rs , ho m e vi sit s, co m m un ity w or ks ho ps , ps yc ho lo gi ca l a ss es sm en t Ci ob an u et a l.,1 8 2 01 4 Co m bi na tio n of sm al le r m on th ly ca sh , l ar ge r c as h at tr ea tm en t co m pl et io n, a nd v ar ia bl e tra ns po rt re im bu rs em en t Ye s: cl in ic v isi ts a nd /o r t re at m en t co m pl et io n; N R 77 3 48 9 20 Vo uc he rs fo r f oo d/ hy gi en e pr od uc ts , ot he r s up po rt (c lo th es , w oo d fo r co ok in g) . P ro vi de d to o nl y a su bs et of th e in te rv en tio n gr ou p Lu e t a l.,1 9 2 01 5 M on th ly c as h tra ns fe r a nd tra ns po rt at io n su bs id y Ye s: cl in ic v isi ts ; c as h de liv er ed by th e pr og ra m m e st aff a t t he co m m un ity h ea lth c en tre o r d ist ric t ce nt re fo r d ise as e co nt ro l 25 3 N A N A N on e U kw aj a et a l.,1 6 2 01 7 M on th ly c as h tra ns fe r e qu iv al en t t o m ed ia n di re ct c os t f or tu be rc ul os is ca re . A pp oi nt m en ts fo r t ub er cu lo sis pa tie nt s r ec ei vi ng c as h ar ra ng ed to n ot c oi nc id e w ith th e co nt ro l gr ou p Ye s: cl in ic v isi ts ; c as h de liv er ed at th e cl in ic b y th e tra in ed st aff m em be r 19 3 19 3 11 N on e (c on tin ue s. . . ) Bull World Health Organ 2018;96:471–483| doi: http://dx.doi.org/10.2471/BLT.18.208959476 Systematic reviews Cash interventions to improve tuberculosis outcomes Aaron Richterman et al. amount of cash distributed ranged from Int$ 193–858. Two studies chose the amount of cash based on previous work estimating local tuberculosis- associated household costs,15,16 including the CRESIPT project in Peru, the only identified randomized control trial.15 The CRESIPT project distributed cash using bank deposit (hypothesizing that opening a bank account was empower- ing to the study subjects),15 whereas other studies used actual cash16,17,19,20 or did not report method of delivery.18,21 Four studies included some additional non-cash co-intervention, including home visits, community meetings, food vouchers and psychological interven- tion.15,17,18,21 Tuberculosis-sensitive interventions Only one study described a tuberculosis- sensitive intervention, a nation-wide retrospective cohort study in Brazil of tuberculosis patients in the Bolsa Familia programme. The programme is a monthly cash transfer to poor people that is conditional on attending antenatal care, nutrition and vaccine monitoring for their children and that their young children attend school.22 People with newly diagnosed non- MDR tuberculosis who received cash during treatment were compared to those who were eligible for cash at the time of treatment, but did not receive it, because of administrative delays. The average amount of total cash delivered to the intervention group was Int$ 101, representing an estimated 3.1% of an- nual individual income. Cash could be claimed by the patient monthly using a designated bank card. Outcomes Most studies (5) reported the primary outcome of treatment success,15,16,18–20 one reported treatment completion21 and two reported microbiologic cure (Table 3).17,22 Four studies controlled for potential confounders.16,18,19,22 Two of the three studies that reported loss to follow-up found significantly less loss to follow-up in the intervention group.15,16,18 Of the four studies which reported mortality, none found a dif- ference between the intervention and control groups.15–18 Bias Table 4 shows the risk of bias within in- dividual observational studies and three Au th or , y ea r Ca sh tr an sf er in te rv en tio n Co nd iti on al in te rv en tio n; m et ho d of ca sh d el iv er y M ax im um ca sh , I nt $a Av er ag e ca sh , I nt $a Av er ag e ca sh a s pe rc en t o f a nn ua l in co m eb Ad di tio na l i nt er ve nt io ns c W in gfi el d et a l.,1 5 2 01 7 Ca sh tr an sf er s t hr ou gh ou t tre at m en t t o de fra y av er ag e ho us eh ol d tu be rc ul os is- as so ci at ed co st s, es tim at ed to b e 10 % a nn ua l ho us eh ol d in co m e in th is se tt in g Ye s: de ta ils u ns pe ci fie d; d ep os it in to b an k ac co un t 43 6 35 5 13 (3 .6 )d H ou se ho ld v isi ts w ith e du ca tio n on tu be rc ul os is tra ns m iss io n, tr ea tm en t, an d pr ev en tiv e th er ap y an d on ho us eh ol d fin an ce s. Co m m un ity m ee tin gs fo r i nf or m at io n, su pp or t, em po w er m en t a nd st ig m a re du ct io n Tu be rc ul os is -s en si ti ve in te rv en ti on s To rre ns e t a l.,2 2 2 01 6 M on th ly c as h to fe m al e he ad o f ho us eh ol d as p ar t o f B ol sa Fa m ili a pr og ra m m e Ye s: 1) A tte nd an ce a t p re na ta l, po st na ta l m on ito rin g se ss io ns 2) N ut rit io n an d va cc in e m on ito rin g fo r c hi ld re n 3) S ch oo l a tte nd an ce ; W ith dr aw al u sin g de sig na te d de bi t ca rd d ist rib ut ed b y pr og ra m m e 22 2 10 1 3. 1 N on e In t$ : in te rn at io na l d ol la rs ; N A: n ot a va ila bl e; N R: n ot re po rte d. a W e co nv er te d th e av er ag e am ou nt o f c as h re ce iv ed p er p at ie nt in to In t$ p ur ch as in g po w er p ar ity c on ve rs io n fa ct or , a nd th en a dj us te d fo r i nfl at io n in to 2 01 6 do lla rs w ith th e lo ca l i nfl at io n co nv er sio n fa ct or .11 b Es tim at ed p er ce nt ag e of a nn ua l i nd iv id ua l i nc om e, u nl es s o th er w ise sp ec ifi ed c Ad di tio na l i nt er ve nt io ns d id n ot in vo lv e ca sh . d Re po rte d pe rc en ta ge o f a nn ua l h ou se ho ld in co m e. (. . . co nt in ue d) Aaron Richterman et al. Cash interventions to improve tuberculosis outcomes Systematic reviews 477Bull World Health Organ 2018;96:471–483| doi: http://dx.doi.org/10.2471/BLT.18.208959 Ta bl e 3. Ou tc om es o f i nc lu de d st ud ie s i n th e sy st em at ic re vi ew o n ca sh in te rv en tio ns to im pr ov e tu be rc ul os is cli ni ca l o ut co m es , 1 99 1– 20 17 Au th or , y ea r Pr im ar y o ut co m e Ou tc om e in di ca to ra Sa m pl e siz e No . p at ie nt s o f w ith p rim ar y o ut co m e OR (9 5% CI ) Ad ju st ed co va ria te s Se co nd ar y o ut co m es (in te rv en tio n ve rs us co nt ro l) In te rv en tio n Co nt ro l In te rv en tio n Co nt ro l Tu be rc ul os is -s pe ci fic in te rv en ti on s Fa rm er e t a l.,1 7 19 91 M ic ro bi ol og ic c ur e 30 30 30 13 79 .0 8 (4 .4 2– 1 41 3. 33 ) N on e Sp ut um p os iti vi ty a t 6 m on th s ( 0% v s 1 3% ); pu lm on ar y sy m pt om s at 1 y ea r ( 7% v s 4 3% ); w ei gh t g ai ne d du rin g fir st ye ar (1 0. 4 lb s v s 1 .7 lb s) ; re tu rn to w or k af te r 1 y ea r (9 3% v s 4 7% ); 18 -m on th m or ta lit y (0 % v s 1 0% ) Ch iri co e t a l.,2 0 20 11 Tr ea tm en t s uc ce ss 80 4 84 7 75 0 66 6 1. 19 (1 .0 3– 1. 37 ) N on e N on e Ro ch a et a l.,2 1 20 11 Tr ea tm en t co m pl et io n 30 7 15 54 29 8 14 14 3. 28 (1 .6 5– 6. 51 ) N on e H ea lth in su ra nc e re gi st ra tio n (9 8% v s 36 % ); co nt ac t s cr ee ni ng (9 6% v s 8 2% ); ra pi d M D R- tu be rc ul os is te st in g (9 2% v s 6 7% ); H IV te st in g (9 7% v s 3 1% ); co nt ac t pr ev en tiv e th er ap y in iti at io n (8 8% v s 3 9% ) an d co m pl et io n (8 7% v s 27 % ) Ci ob an u et a l.,1 8 20 14 Tr ea tm en t s uc ce ss 23 78 24 92 20 81 19 64 2. 00 (1 .6 1– 2. 22 )b Pl ac e of re sid en ce , se x, a ge , o cc up at io n, ho m el es sn es s, H IV , t yp e of tu be rc ul os is Tr ea tm en t f ai lu re (2 % v s 5% ); lo ss to fo llo w -u p (5 % vs 1 0% ); de at h (5 % v s 6 % ) Lu e t a l.,1 9 2 01 5 Tr ea tm en t s uc ce ss 32 90 24 13 N R N R 1. 65 (1 .4 0– 1. 95 )b G en de r, ag e, o cc up at io n, pe r c ap ita G D P of d ist ric t, de ns ity o f p op ul at io n, tu be rc ul os is sp ec ia lis ts p er 10 0 pa tie nt s N on e U kw aj a et a l.,1 6 20 17 Tr ea tm en t s uc ce ss 12 1 17 3 10 4 12 3 2. 30 (1 .2 0– 4. 30 )b Se x, a ge , r ur al /u rb an re sid en ce , n ew /p re vi ou sly tre at ed tu be rc ul os is, H IV , sm ea r- po sit iv ity Lo ss to fo llo w -u p (5 % vs 2 0% ); tra ns fe rre d ou t (1 % v s 0 % ); de at h (7 % v s 6% ); sm ea r n eg at iv e at 2 m on th s ( 88 v s 9 2) (c on tin ue s. . . ) Bull World Health Organ 2018;96:471–483| doi: http://dx.doi.org/10.2471/BLT.18.208959478 Systematic reviews Cash interventions to improve tuberculosis outcomes Aaron Richterman et al. studies met criteria for high overall risk of bias.17,20,21 We deemed the randomized control trial15 not to have a high overall risk of bias, as only the domain attri- tion showed high risk: 37% (105/282) of patients were lost to follow-up or not evaluated. The other six domains had a low risk. The funnel plot of studies included in meta-analysis did not show evidence of publication bias (Fig. 2). Summary effect measures Fig. 3 shows the forest plot of the re- maining tuberculosis-specific studies af- ter excluding studies at high overall risk of bias. Patients receiving tuberculosis- specific cash transfer were more likely to have a clinical positive outcome than patients in the control groups (OR: 1.77; 95% confidence interval: 1.57–2.01), with I2 = 0% (Q test P = 0.44). Discussion The findings of this systematic review and meta-analysis suggest that cash transfer interventions for patients in low- and middle-income countries initiating tuberculosis treatment may improve clinical outcomes. All studies reported improvement in treatment outcomes. However, the overall evidence is weak because we only identified one eligible randomized control trial. Ad- ditionally, half of the studies included some non-cash co-intervention and thus some of the positive effects seen may be related to the pooled effects of cash and non-cash interventions. There are several possible mecha- nisms by which cash transfer interven- tions may improve clinical outcomes for tuberculosis patients during treat- ment.6,25 Both tuberculosis-specific and tuberculosis-sensitive cash transfer interventions can act as direct poverty- reduction measures by offsetting costs caused by the disease. These costs include both direct costs of treatment such as clinic fees, medication costs, travel and/or food, as well as indirect costs incurred through loss of wages. In particular, catastrophic costs, defined as tuberculosis-related costs which exceed 20% of the household’s annual income, have been associated with adverse clinical outcomes.1,2,26 Two studies have found that, on average, a person with tu- berculosis in a low- and middle-income country will experience catastrophic costs as a result of the illness.2,27 In this review, one tuberculosis-specific Au th or , y ea r Pr im ar y o ut co m e Ou tc om e in di ca to ra Sa m pl e siz e No . p at ie nt s o f w ith p rim ar y o ut co m e OR (9 5% CI ) Ad ju st ed co va ria te s Se co nd ar y o ut co m es (in te rv en tio n ve rs us co nt ro l) In te rv en tio n Co nt ro l In te rv en tio n Co nt ro l W in gfi el d et a l.,1 5 20 17 Tr ea tm en t s uc ce ss 13 5 14 7 87 78 1. 60 (0 .9 9– 2. 59 ) N on e Lo ss to fo llo w -u p (1 6% v s 18 % ); de at h (4 % v s 4 % ) Tu be rc ul os is -s en si ti ve in te rv en ti on s To rre ns e t a l.,2 2 20 16 M ic ro bi ol og ic c ur e 57 88 14 67 47 52 11 28 1. 07 (1 .0 4– 1. 11 )b Ag e, e th ni ci ty , di ab et es m el lit us , H IV , e xt ra pu lm on ar y tu be rc ul os is, se lf- ad m in ist er ed tr ea tm en t, ru ra l a re a, n um be r of ro om s i n ho us e, in ap pr op ria te fl oo r m at er ia l, b as el in e ho us eh ol d m on th ly p er ca pi ta in co m e < U S$ 20 , ill ite ra cy N on e CI : c on fid en ce in te rv al ; G D P: g ro ss d om es tic p ro du ct ; H IV : h um an im m un od efi ci en cy v iru s; lb s: po un ds ; M D R: m ul tid ru g re sis ta nt ; N R: n ot re po rte d; O R: o dd s r at io ; U S$ : U ni te d St at es d ol la rs . a Th e de fin iti on s o f t he o ut co m es w er e: tr ea tm en t s uc ce ss w as p os iti ve c lin ic al o ut co m e; tr ea tm en t c om pl et io n w as if a st ud y di d no t r ep or t t re at m en t s uc ce ss ; a nd m ic ro bi ol og ic c ur e w as if a st ud y di d no t r ep or t t re at m en t s uc ce ss o r t re at m en t co m pl et io n. b D er iv ed fr om m ul tiv ar ia bl e re gr es sio n m od el s. (. . . co nt in ue d) Aaron Richterman et al. Cash interventions to improve tuberculosis outcomes Systematic reviews 479Bull World Health Organ 2018;96:471–483| doi: http://dx.doi.org/10.2471/BLT.18.208959 intervention provided cash equivalent to 173% of estimated annual individual income,17 four provided cash equivalent to 10–20% of estimated annual indi- vidual income,15,16,18,21 and two of these studies also reported the intervention as percentage of annual household income, between 3–6%.15,21 The single tuberculo- sis-sensitive intervention we identified provided cash equivalent to 3.8% of estimated annual individual income. The difference between tuberculosis- specific and tuberculosis-sensitive in- terventions may reflect the findings that sensitive interventions are less likely to be effective and affordable by countries for offsetting tuberculosis-associated catastrophic costs than specific interven- tions.27 However, tuberculosis-sensitive interventions also have the advantage of a broader poverty reduction impact, which might improve household eco- nomic resilience before a household member develops active tuberculosis infection. Beyond simply offsetting costs, cash transfer interventions may also serve as an additional incentive for health-seek- ing behaviour, particularly when distri- bution is conditional on clinical follow- up or medication adherence.28–30 Several systematic reviews have found a positive effect of conditional cash transfers in low- and middle-income countries on health behaviours and outcomes, includ- ing increased use of preventative ser- vices, improved childhood nutritional status, decreased self-reported episodes of illness and decreased HIV preva- lence.25,30,31 Another systematic review found that the impact of unconditional cash transfers on health services use and health outcomes was uncertain.28 None of the interventions we identified had a completely unconditional cash transfer intervention. The incentive of a conditional intervention may be particularly important in tuberculosis care, where consistent adherence to a multiple-drug regimen for a prolonged treatment course is essential for optimal treatment outcomes. However, a meta- analysis of the effect of incentives and/ or enablers on medication adherence in tuberculosis was largely inconclu- sive, but primarily identified studies in high-income countries, where financial interventions may have less effect.32 Tuberculosis-sensitive interventions are likely to lack a tuberculosis-specific incentive, although they may include other conditional elements unrelated to Table 4. Bias within included observational studies in the systematic review on cash interventions to improve tuberculosis clinical outcomes, 1991–2017 Study, year Category, no. of stars Selectiona Comparabilityb Outcomec Farmer et al.,17 1991 3 0 2 Chirico et al.,20 2011 3 0 1 Rocha et al.,21 2011 2 0 0 Ciobanu et al.,18 2014 3 2 2 Lu et al.,19 2015 3 2 2 Torrens et al.,22 2016 3 2 3 Ukwaja et al.,16 2017 3 2 2 a A study could be awarded a maximum of four stars for this category. b A study could be awarded a maximum of two stars for this category. c A study could be awarded a maximum of two stars for this category. Note: We used Newcastle-Ottawa Scale to assess bias in observational studies. The more stars the study received the lower the risk of bias. Fig. 2. Publication bias of studies included in the meta-analysis on cash interventions to improve tuberculosis clinical outcomes, 1991–2017 SE (l og [O R] ) 0 0.1 0.2 0.3 0.4 0.5 OR 0.01 0.1 1 10 100 OR: odds ratio; SE: standard error. Note: The dashed vertical line represents the summary OR generated through random effects meta- analysis. Fig. 3. Likelihood of a positive clinical outcome for tuberculosis-specific cash interventions to improve tuberculosis clinical outcomes, 1991–2017 Study, year OR (95% CI) Ciobanu et al, 2014 2.00 (1.61–2.22) Lu et al, 2015 1.65 (1.40–1.95) Ukwaja et al, 2017 2.30 (1.20–4.30) Wingfield et al, 2017 1.60 (0.99–2.59) Total 1.77 (1.57–2.01) l2 = 0% Favors control Favors cash 0.2 0.5 1 2 5 CI: confidence interval; OR: odds ratio. Note: We excluded three studies with a high overall risk of bias.17,20,21 Bull World Health Organ 2018;96:471–483| doi: http://dx.doi.org/10.2471/BLT.18.208959480 Systematic reviews Cash interventions to improve tuberculosis outcomes Aaron Richterman et al. صخلم ليلتحو ةيجهنم ةعجارم :يوئرلا لسلا ضرلم ةيريسرلا جئاتنلا ينسحتل ةيدقنلا تلاخدتلا ينستح لىإ ةيعاسلا ةيدقنلا تلايوحتلا تلاخدت مييقت ضرغلا ضفخنلما لخدلا تاذ نادلبلا في طشنلا يوئرلا لسلا جلاع جئاتن .طسوتلماو ،®Embaseو ،®PubMed نم لك في ثحبلاب انمق دقل ةقيرطلا نع ،ClinicalTrials.govو ،Cochrane Library ةبتكمو تلوانت يتلاو ،2017 بآ/سطسغأ 4 ىتح ةروشنلما تاساردلا في طشنلا يوئرلا لسلا جلاع ءانثأ ةيدقنلا تلايوحتلا تلاخدت ةيلولأا انجئاتن تناكو .طسوتلماو ضفخنلما لخدلا تاذ نادلبلا لماكإ وأ ،جلاعلا حاجن انهأب اهفيرعت مت ،ةيبايجإ ةيريسر ةجيتن ليوتح لماعم مادختسابو .يجولويبوركيلما فياعتلا وأ ،جلاعلا لكل ملتسلما يدقنلا غلبلما ليوحتب انمق ،ةيئاشرلا ةوقلا لداعت )OR( لماتحلاا ةبسن انبسح .ليود رلاود لىإ ةسارد لك في ضيرم .يئاوشعلا يولتلا ليلحتلا مادختساب ةيلولأا جئاتنلل في اهنيمضتل ةيلهلأا يرياعم عم تاسارد نيماث تقفاوت جئاتنلا ضرمب صالخا لخدتلا مييقتب تاسارد عبس تماق .ةعجارلما ًارلاود 858 لىإ 193 نم حواتري يدقن غلبم طسوتم عم ،لسلا ،لسلا ضرلم ساسلحا لخدتلا تاساردلا ىدحإ تميقو .ًايلود تاسارد عبرأ تلمش .ًايلود ًارلاود 101 هردق غلبم طسوتمب جئاتن تاساردلا عيجم ترهظأ .ةكترشلما ةيدقنلا يرغ تلاخدتلا دعب .ةيعجرلما ةعومجلما نم لخدتلا ةعومجلم لضفأ ةيلوأ ضىرلما ناك ،زيحتلل ةيلاع ةروطخ تاذ تاسارد ثلاث داعبتسا قيقحتل ةضرع رثكأ لسلاب ةصاخ ةيدقن تلايوتح نوقلتي نيذلا ةبسن( ةيعجرلما تاعومجلما في ضىرلما نم ةيبايجإ ةيريسر جئاتن .)2.01 لىإ 1.57 نم :95٪ ةقثلا لصاف ؛1.77 :ةيحجرلأا لخدلا تاذ نادلبلا في ضىرلما نأ لىإ ةحاتلما ةلدلأا يرشت جاتنتسلاا نم مهجلاع ءانثأ ةيدقن غلابم نوقلتي نيذلا ، طسوتلماو ضفخنلما ةيريسر جئاتن قيقحتل ةضرع رثكأ مه ،طشنلا يوئرلا لسلا ضرم تلايوحتلا تلاخدت جمدل هاتجلاا جئاتنلا هذه معدت .ةيبايجإ .لسلا ضرم جلاع جمارب نمض ةيعماتجلاا ةيمالحا مظن في ةيدقنلا tuberculosis, as in the case of the Bolsa Familia programme.22 The studies showed substantial heterogeneity in study design. However, there was no measured heterogeneity within the subset of studies with tubercu- losis-specific interventions that were not at high overall risk of bias. Although fac- tors related to the population, setting and intervention could cause heterogeneity in the effect size of the interventions, the available information from the limited number of studies did not allow us to determine the impact of these variables. Whether cash transfers or goods and services, such as direct provision of food, vocational training, psychologic support and housing programmes, are preferable to improve health-related and other outcomes is currently under debate.33–35 A recent meta-analysis found that non- cash socioeconomic interventions, pre- dominantly food provision, may improve clinical outcomes in active tuberculosis.36 To better understand which forms of social protection are most effective at improving clinical outcomes for tuber- culosis, non-cash strategies should be studied comparatively and in combina- tion with cash transfer interventions. While beyond the scope of this review, the impact of cash transfer in- terventions on household and national or subnational outcomes, like contact screening and overall tuberculosis incidence, must also be considered. For example, a multivariable analysis found that municipalities in Brazil with higher coverage by the Bolsa Familia programme had a significant reduction in tuberculosis incidence compared to those with lower coverage.37 In conclusion, we found some evi- dence that cash transfer interventions improve treatment outcomes in patients with active pulmonary tuberculosis in low- and middle-income countries, although the overall quality of this evidence is low. These findings support calls by WHO and others to incorporate cash transfer interventions into social protection schemes within tuberculosis treatment programmes.1,6 In addition, high-quality research is needed to better understand the effectiveness of tuberculosis-specific and tuberculosis- sensitive cash transfer interventions, including understanding of the optimal amount, conditional feature, delivery method and implementation strategy. ■ Acknowledgements JJ, LBN and JW contributed equally to this work. Competing interests: None declared. 摘要 通过现金干预以改善肺结核的临床疗效：系统评价和荟萃分析 目的 评估通过现金转移干预措施以改善中低收入国家 活动性肺结核的治疗效果。 方 法 在 PubMed®、Embase®、 考 克 兰 图 书 馆 和 美 国 临 床 试 验 数 据 库 (ClinicalTrials.gov) 搜 索 截 至 2017 年 8 月 4 日发表的研究时，我们发现了报道 的中低收入国家活动性肺结核治疗期间的现金转移干 预。我们的主要成果是积极的临床疗效，因此而被定 义为治疗成功、治疗完成或微生物学治疗。通过使用 购买力平价换算，我们将每项研究中每名患者接收的 现金数额换算成国际美元 (Int$)。我们采用随机效应 荟萃分析法为主要结果计算了优势比。 结果 其中，有八项研究符合纳入审查的资格标准。有 七项研究评估了结核病专项干预，其平均现金数额 从 193 至 858 国际美元不等。有一项研究评估了结核 病敏感干预，其平均现金数额为 101 国际美元。有四 项研究包含非现金共同干预。所有研究均表明干预组 的主要结果优于对照组。通过排除三项具有高度偏见 风险的研究，接收结核病专项现金转移的患者比控制 组中的患者更可能出现积极的临床疗效（或 ：1.77 ； 95% 置信区间 ：1.57–2.01)。 结论 有效证据显示中低收入国家的患者在治疗活动性 肺结核期间接收现金干预更有可能拥有积极的临床疗 效。这些发现支持将结核病治疗方案中的现金转移干 预纳入社会保障计划中。 Bull World Health Organ 2018;96:471–483| doi: http://dx.doi.org/10.2471/BLT.18.208959 481 Systematic reviews Cash interventions to improve tuberculosis outcomesAaron Richterman et al. Résumé Des interventions financières pour améliorer les résultats cliniques de la tuberculose pulmonaire: revue systématique et méta-analyse Objectif Évaluer le rôle des interventions de transfert de fonds pour améliorer les résultats du traitement de la tuberculose pulmonaire active dans les pays à revenu faible et intermédiaire. Méthodes Nous avons recherché, dans les bases de données de PubMed®, d’Embase®, de ClinicalTrials.gov et de la Cochrane Library, des études publiées jusqu’au 4 août 2017 qui mentionnaient des interventions de transfert de fonds durant le traitement de la tuberculose pulmonaire active dans des pays à revenu faible et intermédiaire. Le critère principal pris en compte était l’obtention d’un résultat clinique positif, défini comme la réussite du traitement, l’achèvement du traitement ou la guérison microbiologique. À l’aide du taux de conversion en parité de pouvoir d’achat, nous avons converti le montant des fonds versés par patient dans chaque étude en dollars internationaux ($ int.). Nous avons calculé le rapport des cotes (RC) pour le critère principal au moyen d’une méta-analyse à effets aléatoires. Résultats Huit études remplissaient les critères d’admissibilité permettant d’être incluses dans notre revue. Sept études évaluaient une intervention spécifique à la tuberculose, avec un montant moyen versé compris entre 193 et 858 $ int. Une étude évaluait une intervention prenant en compte la tuberculose, avec un montant moyen de 101 $ int. Quatre études comprenaient des co-interventions non financières. Toutes les études montraient un critère principal plus souvent atteint dans le groupe expérimental que dans le groupe témoin. Après avoir exclu trois études qui présentaient un risque de biais important, il est ressorti que les patients qui bénéficiaient de transferts de fonds spécifiques à la tuberculose étaient plus susceptibles d’avoir un résultat clinique positif que les patients des groupes témoins (RC: 1,77; intervalle de confiance de 95%: 1,57-2,01). Conclusion Les données disponibles suggèrent que les patients des pays à revenu faible et intermédiaire qui reçoivent des sommes d’argent durant leur traitement contre la tuberculose pulmonaire active sont plus susceptibles d’avoir un résultat clinique positif. Ces conclusions vont dans le sens de l’intégration d’interventions de transfert de fonds dans les plans de protection sociale des programmes de traitement de la tuberculose. Резюме Финансовая помощь как средство улучшения клинических исходов лечения туберкулеза легких: систематический обзор и метаанализ Цель Оценить влияние финансовой помощи на улучшение результатов лечения активного туберкулеза легких в странах с низким и средним уровнем дохода. Методы Авторы провели поиск в базах данных PubMed®, Embase®, Кохрановской библиотеке (Cochrane Library) и в реестре ClinicalTrials.gov на предмет исследований, опубликованных до 4 августа 2017 года, в которых сообщалось об оказании финансовой помощи в ходе лечения активного туберкулеза легких в странах с низким и средним уровнем дохода. В качестве основного результата рассматривался положительный клинический исход, определяемый как эффективное лечение, завершение лечения или микробиологическое излечение. Используя коэффициент пересчета паритета покупательной способности, авторы перевели количество денежных средств, полученных каждым пациентом в рамках каждого исследования, в международные доллары. Авторы рассчитали отношение шансов (ОШ) для основного результата, используя метаанализ случайных эффектов. Результаты Восемь исследований соответствовали критериям приемлемости для включения в обзор. В семи исследованиях оценивалась финансовая помощь, связанная с лечением туберкулеза, со средним количеством денежных средств в диапазоне от 193 до 858 международных долларов. В одном исследовании оценивалась финансовая помощь, связанная с лечением туберкулеза, со средним количеством денежных средств, равным 101 международному доллару. Четыре исследования включали неденежные совместные вмешательства. Во всех исследованиях для группы вмешательства наблюдался лучший основной результат по сравнению с контрольной группой. После исключения трех исследований с высоким риском систематической ошибки было обнаружено, что у пациентов, получающих финансовую помощь, связанную с лечением туберкулеза, чаще наблюдался положительный клинический исход, чем у пациентов в контрольных группах (ОШ: 1,77; 95%-й ДИ: 1,57–2,01). Вывод Имеющиеся данные свидетельствуют о том, что у пациентов в странах с низким и средним уровнем дохода, получающих финансовую помощь во время лечения активного туберкулеза легких, чаще наблюдается положительный клинический исход. Эти результаты подтверждают рациональность включения финансовой помощи в схемы социальной защиты в рамках программ лечения туберкулеза. Resumen Intervenciones de efectivo para mejorar los resultados clínicos de la tuberculosis pulmonar: revisión sistemática y metanálisis Objetivo Evaluar las intervenciones de transferencias de efectivo para mejorar los resultados del tratamiento de la tuberculosis pulmonar activa en los países con ingresos entre bajos y medios. Métodos Se realizaron búsquedas en PubMed®, Embase®, Cochrane Library y ClinicalTrials.gov en busca de estudios publicados hasta el 4 de agosto de 2017 que informaran sobre intervenciones de transferencias de efectivo durante el tratamiento de la tuberculosis pulmonar activa en países con ingresos entre bajos y medios. El resultado principal fue un resultado clínico positivo, definido como éxito del tratamiento, finalización del tratamiento o curación microbiológica. Con el factor de conversión de paridad del poder adquisitivo, se convirtió la cantidad de dinero en efectivo recibido por paciente dentro de cada estudio en dólares internacionales. Se calculó el cociente de posibilidades (CP) para el resultado principal mediante un metanálisis de efectos aleatorios. Resultados Ocho estudios cumplieron los criterios de elegibilidad para ser incluidos en la revisión. Siete estudios evaluaron una intervención específica para la tuberculosis, con una cantidad promedio de efectivo que osciló entre 193 e 858 dólares internacionales. Un estudio evaluó una intervención sensible a la tuberculosis, con una cantidad promedio de 101 dólares internacionales. Cuatro estudios incluían Bull World Health Organ 2018;96:471–483| doi: http://dx.doi.org/10.2471/BLT.18.208959482 Systematic reviews Cash interventions to improve tuberculosis outcomes Aaron Richterman et al. cointervenciones no monetarias. Todos los estudios mostraron mejores resultados principales para el grupo de intervención que para el grupo control. Después de excluir tres estudios con alto riesgo de sesgo, los pacientes que recibieron una transferencia de efectivo específica para la tuberculosis tuvieron mayores probabilidades de obtener un resultado clínico positivo que los pacientes de los grupos control (CP: 1,77; intervalo de confianza (IC) del 95%: 1,57 a 2,01). 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