Search results:
The flow diagram of the selection process is shown in figure 1. In total of 5114 potentially relevant articles were found after data base search. One additional citation was found through a personal search, of this number, 1922 articles were excluded as duplicates by Endnote X8. After title and abstract screening 3041 article were excluded (201 duplicates found manually, 2840 irrelevant). Two unpublished data were included to the 152 text eligible articles to full text screening, in addition we added 2 articles were added manually. A total of 29 articles were therefore reviewed in detail and included in the analysis. The main characteristics of these studies are summarized in table 1. The inter-rater agreement for inclusion was κ=0.95 and for the quality assessment was κ=0.8
Study characteristics
Qualitative synthesis included 29 studies conducted in 15 countries; six studies from India, five from China, four from Indonesia, one study from each of the following countries (Egypt, Zimbabwe, Nepal, Lao PDR, Ghana, Pakistan, Vietnam, Cambodia, Peru, and Cavite), and two studies from each Uganda, and South Africa. Of included studies there were 5 cohort studies [12], [13], [17], [26] &[27] . One mixed methods study [28], while the other 23 studies were cross-sectional. Male sex presentation ranged from 30% [29], to 77% [18]. The sample size ranged from 50 [29], to 1178 [30]. The tool used for estimation of the cost survey were either WHO TB cost survey tool, [5], [15], [30], [31], [32], [33], [34], [35], [36], [37], [38], [39], [40] & [44], or adapted WHO tool to Indonesian context [12] & [41], or structured questionnaire [17], [26], [42], [43], pre-coded interview scheduled [18],or tool of stop TB partnership, [13], [27], [28],or headcount tool [44], or Lumley T. survey [14], or TB coalition tool [16]. On the other hand, there were two studies not mentioned the tool used [29], [45]. The percent of patients facing catastrophic cost at cut off point 20% ranged from 4% in study of Mihir et al, study [46], to 87% in study of Wang et al, [44]. Regarding the percent of MDR-TB patients that facing catastrophic cost, they ranged from (68%), reported by Mullerpattan 2019 to (90%), reported by Collin et al, 2018 however DS-TB patients ranged from 24%, in the study of Gadallah,2018 to 42%, in the study of Rebecca L.Walctt, 2020. The percent of ACF patient facing catastrophic cost ranged from 9% to 44%, however the percent of PCF patient ranged from 29% to 61% [18] & [39]. Hardship financing was discussed only in two studies[14] [45]. Seven studies discussed coping cost [16], [27], [30], [33], [35], [37] & [45]. Regarding the quality score, it was ranged from (3- unsatisfactory) [29] to (9-Very good) [34]. The Good score ranged from 7 to 8 pints, was among thirteen studies [5], [16], [17], [26], [28], [31], [32], [33], [37], [38], [39], [41] & [45]. While Satisfactory score which ranged from 5 to 6 points, was illustrated in the remaining fourteen studies, [12], [13], [14], [15], [18], [27], [30], [35], [36], [40], [42], [43], [44] & [45].
Publication bias:
The 29 studies reported the catastrophic cost at 20% were be assessed for the risk of bias by the funnel plot and Eggers’ test [t = -1.188, P-value= 0.24], which revealed the absence of asymmetry and decline the presence of publication bias. Fig. 2
1. Primary outcome
1.1 Catastrophic cost at cut-off point 20%
The pooled prevalence of catastrophic cost among 11750 TB patients included in 29 studies at cut-off point of 20% was 43% (95% CI:34-52) with high heterogeneity (I2 = 99%). Fig. (3) To identify the cause of this substantial heterogeneity we conducted meta-regression. Predictors were sex, country where the study conducted (had high incidence vs none)[23], drug sensitivity (DS or MDR± HIV), and quality of the study. The model was significant P<0.0127, R2=51.57%. This model explained more than 50% of the reported heterogeneity. The identified predictors country (high vs low incidence) (β=-0.194, P=0.04) and type of patients regarding drug sensitivity (DS or MDR) and HIV co-infection (β=0.289, P=0.026).
In this study, there are multiple main predictors of catastrophic cost like food and nutritional supplements [33-35],travel and transportation [30, 32, 45], age category [26, 28, 32], employment status [26, 32, 36, 41, 44], the socioeconomic status[13, 26, 27, 32, 41, 44, 47], MDR or HIV positive [28, 32, 35, 47], male gender, [26, 27, 44], and duration of hospitalization [13, 28, 32, 44, 45].
1.2 Coping strategy
In response to balance the enormous financial burden they encounter, the TB-affected families may adopt some coping strategies. Borrowing money, taking out loans, pledging gold and jewels, bringing their children out of schools or selling assets are options to compensate the income loss and the high out-of-pocket expenses [37, 45]. All these approaches are referred to as “dissaving” which is the core of the hardship financing dilemma.
1.3 Pooled proportion of catastrophic cost at 20% among different subgroups
1.3.1 Pooled proportion of catastrophic cost at 20% among TB drug sensitive
The pooled proportion of patients facing catastrophic cost was 39%, 95CI (28-51%), the reported heterogeneity was 99%. After removing outliers, the pooled proportion of 11 studies recruited 3492 patients dropped to 32%, 95% CI [29 – 35]. The pooled prevalence of DS-TB patients facing catastrophic costs ranged from 24%, 95%CI [19 – 30] in the study of Gadallah,2018 [27] to 42%, 95% CI [35 – 49] in the study of Rebecca L.Walctt, 2020 [13].The heterogeneity of the included studies was as follows; I2 = 70%, P < 0.01. (Table. 2)
1.3.2 Pooled prevalence according to TB drug resistant
With a heterogeneity of 92%, the pooled proportion of TB affected household of MDR patients facing catastrophic cost among 1879 patients was 78%, 95%CI, [86%-86%]. After removing outliers, the pooled proportion of patients facing catastrophic cost among 574 patients with MDR reached 80% 95%CI [74-85%], I2=54%. The highest proportion (90%) reported by Collin et al, 2018[40], while the lowest proportion (68%) reported by Mullerpattan 2019 [29]. (Table. 2)
1.3.3 Pooled proportion of TB-HIV co-infected patients facing catastrophic cost at 20%
The pooled proportion of 796 TB patients with HIV facing catastrophic cost at 20% was 76%, 95%CI [ 65 -85%], with a heterogeneity of 88%. After conducting leave-one out sensitivity analysis, the study of Don Mudzengi et al 2017 [16], removed. The heterogeneity dropped to 0% and the pooled proportion patients facing catastrophic cost has increased to 81%, 95%CI [78 – 84] as it illustrated in. (Table.2)
1.3.4 Pooled proportion of TB facing catastrophic cost at 20% through active case finding (ACF)
The proportion of patients facing catastrophic cost among 491 patients exposed active case finding ranged from 9%, 95%CI [7-15%] to 62%, 95%CI [45-77%]. After subgroup analysis based on the country where the ACF was implemented (inside/outside India). The pooled proportion was 10% 95%CI [7-14%], I2= 0% inside India and 48%, 95CI(25-72%) I2 86% outside India. (Table.2)
1.3.5 Pooled proportion of TB facing catastrophic cost through passive case finding (PCF)
The proportion of patients facing catastrophic cost among 638 patients during passive case finding ranged from 12%, 95%CI [8-17%] to 45%, 95%CI [35-55%]. The pooled proportion was 42%, 95%CI [35-50%]; It is worthy to note that heterogeneity was 94%. We further subdivided the studies according to the studied country (inside/outside) India. The pooled proportion of TB household facing catastrophic cost was 19% 95CI (7-41%), I2=95% while outside India 45 95CI(37-53%), I2=0%. (Table.2)
2. Secondary Outcome
1.1 Proportion of direct cost to the total cost
1.1.1 Pooled prevalence according to drug sensitive
The proportion of the mean direct cost to the mean total cost addressed in 6 studies, the pooled proportion of direct to total cost at catastrophic cost of 20% was not calculated as the heterogeneity was high. The proportion was variants, two studies reported similar proportions, Tomeny, 2020[15] & Collins Timire, 2020 [47] with a proportion of 41% and 43% respectively. However, higher proportion 52% reported among Chittamany2020[33] and Nhung, 2018[37]. Two other extreme values reported, 33% by Fuady 2018 [41] and 65% reported by Muttamba, 2020 [30].
1.1.2 Pooled proportion of direct cost in MDR
The proportion of the mean direct cost to the mean total cost at 20% addressed in 7 studies, ranged from 26% in Chittamany, 2020 [33] to 93% in Yang, 2020[32]. Low proportions were observed in Fuady, 2018[41], Tomeny, 2020 [15], and Collins Timire, 2020 [47] with proportion of 32%, 34% and 49% respectively, while high proportion also reported in Muttamba, 2020[30], with 66% and in Nhung, 2018[37] with 68%. The pooled proportion of mean direct to total cost was difficult to assess because of the heterogeneity which wasn’t explained even after a meta-regression performed.
1.1.3 Pooled proportion of direct cost to total cost in case of active case finding (ACF)
The pooled proportion of the mean direct cost to the mean total cost was addressed in 3 studies, the pooled proportion of mean direct to mean total cost was 25%, 95%CI [16-37%], I2=83%. After conducting leave one out sensitivity analysis, the Suman Chandra Gurung, 2019 [39], was removed, the pooled proportion dropped to 29%, 95%C1 [20-41%] I2=55%. (Table.2)
1.1.4 Pooled proportion of direct cost to total cost in case of passive case finding (PCF)
The pooled proportion of the mean direct cost to the mean total cost addressed in 4 studies [17, 18, 39, 45], the pooled proportion of mean direct to mean total cost was 37%, 95%C1 [31-42%] I2=0%. (Table.2)
1.1.5 Proportion of direct cost to total cost in case HIV and TB co-infection
The proportion of the mean direct cost to the mean total cost addressed in 2 studies. Don Mudzengi , 2017[16] and his team showed that the proportion of mean direct cost to the mean total cost was 30% among HIV and TB co-infection patients, while a higher proportion reported in Chittamany, 2020[33] with 59%. As we couldn’t pool the study because of the high un-explained heterogeneity.
The pooled proportion of the mean direct cost to the mean total cost addressed in 14 studies, the pooled proportion of mean direct to mean total cost was 55%, 95%CI [43-66%], I2= 99%. After conducting outliers removal, study Mihir P. Rpan, 2020 [46] was excluded, the pooled proportion dropped to 51%, 95%CI [43-66%], I2= 96%. (Table.2)
2.2 Catastrophic Health Expenditure at 10% & Capacity to Pay at 40%
In this study, we have found that there are six studies that also calculated the CHE 10% and the CTP 40%, in addition to their results regarding the CTC 20%.
2.2. 1 Pooled proportion of CHE at 10%:
The pooled proportion of the CHE at 10% were studied also among the studies which they calculated CTC 20%. Three studies [ 2, 27, 32] were included with pooled proportion of 45%, 95%CI [35-56%], I2= 93%. The result after leave one out sensitivity analysis, Fuady, 2018[40], has excluded and the heterogeneity has decreased to reach I2= 28%, while the pooled proportion has increased to 50%, 95%CI [47-54%]. (Table.2)
2.2.2 Pooled proportion of CTP at 40%:
With 63% pooled proportion, 95%CI [40-80%], I2= 96%, three studies measured the CTP at 40% [12, 29, 30] and after the sensitivity test the heterogeneity was I2=0, while the pooled proportion increased to 70%, 95%CI [64-76%]. (Table.2)