1. PHASA Conference 22-29 September 2016
Poorer Health-Related Quality of Life Among Patients Who Report Adverse Events while on Treatment for Drug-Resistant TB in Johannesburg, South Africa  
Denise Evans, Tembeka Sineke, Kate Schnippel, Helena van Aswegen, Rebecca Berhanu, Lawrence Long, Elisabeth Lönnermark, Sydney Rosen
PHASA Conference September 2016
PHASA Confere
nce September 2016

2. Background
South Africa bears a disproportionate share of the world’s epidemic of drug-resistant tuberculosis (DR-TB).
Adverse events are common during treatment of DR-TB.
Some harm quality of life (e.g. abdominal pain, nausea)
Some are disabling (e.g. irreversible hearing loss)
Some are life threatening (e.g. renal failure, psychosis, seizures).
Little is known about health-related quality of life (HRQoL) of patients receiving treatment for DR-TB or the effect of adverse events on HRQoL.

3. Aims Measure the HRQoL of DR-TB patients receiving
outpatient treatment and care using a standardized tool (Short Form 36 Health Survey).
Describe the experience of adverse events (AEs) by patients receiving DR-TB treatment including frequency and characteristics of AEs using a standardized tool.
Compare health-related quality of life among DR-TB patients who reported an adverse event versus those who do not report an adverse event in the past 4 weeks.

4. Methods
Cross-sectional survey of a sub-sample of patients enrolled in a prospective cohort study.
Cohort study enrolled adult (≥ 18) patients who:
Documented laboratory diagnosis of RIF resistant TB.
Initiated DR-TB treatment at the specialized, outpatient TB Focal Point (FP) of Helen Joseph Hospital, Johannesburg, South Africa after March 2013.
Provide informed consent for medical file review.
Sample for HRQoL survey:
Conveniently sampled patients enrolled in cohort study after February 2015.
Willing to participate and provide informed consent.
Outcome:
Poor HRQoL defined as a low Mental Component Score (MCS) or Physical Component Score (PCS): according to scoring instructions and using the median as a cut-off point.

5. Methods (Continued) Survey instruments Statistical analysis
SF-36, questionnaire asking about health-related quality of life in the past 4 weeks.
Part A: All patients, recent symptoms in past four weeks.
Part B: Detailed questions about specific AEs reported in Part A (e.g. hearing loss, psychosis or depression, vertigo, and/or (iv) peripheral neuropathy)
Part C: Validated hearing loss screening tool (HHIE-S) for patients who reported hearing loss in Part A.
Statistical analysis
Log-binomial regression was used to test the association between reporting an adverse event in the last four weeks and a low MCS or PCS. Models adjusted for
age, gender, and time on DR-TB treatment.
Scales were compared to SF-36 scales for healthy adults in Johannesburg from a published study (van Aswegen et al, 2011).

6. Characteristics of Patients with Drug-Resistant Tuberculosis
Description
(N=57)
Gender
Male
Female
n, %
33 (57.9%)
24 (42.1%)
Age, years
≤35
>35
Median, IQR
37 (29-40)
26 (45.6%)
31 (54.6%)
Education
Primary/no education
Higher
47 (82.5%)
10 (17.5%) 
Employment
Employed
Not Employed
35 (61.4%)
22 (38.6%)
Classification
RR-TB
MDR-TB
n,%
42 (73.7%)
15 (26.3%)
Time on TB treatment, months
15.6 ( )
HIV status
Positive
Negative
49 (86.0%)
8 (14.0%)
Baseline CD4 (n=35)
78 ( )
On ART at start of RR-TB treatment
Yes No
21/49 (42.9%)
28/49 (57.1%)
Time on ART treatment, months
20.6 ( )

7. Adverse Events, Stratified by Age Category
More than a third of patients (21/57, 37%) reported an adverse event in the past four weeks.
Total of 24 adverse events described: 7 hearing loss, 2 psychosis or depression, 5 vertigo, and 10 peripheral neuropathy.
Some patients reported more than 1 adverse events

8. SF-36 Scales and Mental and Physical Health Component Summary Scores
Adverse event not reported (n=36)
Adverse event reported (n=21)
P value
Mean SD
Alpha*
Physical functioning
94.7
11.7
0.868
72.1
30.3
0.872
0.0004
Role physical
82.6
29.8
0.839
45.2
45.8
0.837
0.001
Role emotional
80.6
35.9
0.836
30.5
0.854
Energy/vitality
64.7
18.1
0.835
50.5
21.8
0.855
0.009
Emotional well-being
72.6
16.6
0.818
58.1
16.8
0.843
0.002
Social functioning
80.2
25.4
0.830
60.7
23.1
0.849
Pain
84.4
23.5
0.820
69.1
26.7
0.858
0.030
General health
75.7
13.1
0.844
68.8
12.5
0.882
0.041
Norm-based scale
Mental health component summary (MCS)
46.2
11.4
n/a
33.3
12.3
Physical health component summary (PCS)
55.4
5.8
48.4
9.2
0.007

9. Summary Scores
Patients who reported an adverse event (n=21) had significantly lower scales for physical functioning, emotional role, energy, and social functioning and were more likely to have a lower MCS and PCS.
Proportion with lower MCS
Crude RR and 95% CI
Adjusted RR and 95% CI
No adverse event
12/36
1.0 (reference)
Adverse event
16/21
3.3 (1.40 – 7.82)
3.7 (1.62– 8.62)
Proportion with lower PCS
Crude RR and 95% CI
Adjusted RR and 95% CI
No adverse event
14/36
1.0 (reference)
Adverse event
15/21
2.4 (1.09 – 5.33)
2.6 (1.19 – 5.69)
After adjusting for age and gender, the association remains with patients who reported an adverse event were more likely to have lower MCS and PCS

10. SF-36 Scales for Patients on DR-TB Treatment and Healthy Adults
When we compare SF-36 scare for Patients on DR-TB Treatment and Healthy Adults, patients with adverse had poor HRQoL compared to healthy patients

11. Conclusions
Patients who reported an adverse event during DR-TB treatment reported poorer HRQoL (MCS and PCS) than those who did not.
Based on the SF-36 scales, patients with adverse events reported much poorer HRQoL than healthy adults.
These findings are likely to have implications for patients’ clinical, social and economic wellbeing.
Study had several limitations:
Small sample size – continuing to enroll patients until December 2016.
Did not have a comparison group that was representative of study population.
Study population has high rates of HIV co-infection (86%), with more complicated HIV/ART cases.

12. Next steps…
SF-36 could be used as a screening tool to identify patients who require referral (e.g. depression or hearing loss) or targeted interventions.
We plan to assess whether patients with poor HRQoL, in particular those with poor MCS or poor PCS, have poorer treatment outcomes (e.g. treatment failure, LTFU) and identify which patients may require rehabilitation (e.g. hearing loss) after treatment.
We plan to enroll comparison cohorts.
Talk about new amendment to look at patients from other sites

13. Acknowledgments Denise Evans Sydney Rosen Lawrence Long Tembeka Sineke
Kathryn Schnippel
Heleen van Aswegen
Rebecca Berhanu
Elisabet Lönnmark
Patients and staff at CHRU and Themba Lethu Clinic – Helen Joseph Hospital
Talk about new amendment to look at patients from other sites with differ
This presentation was made possible by the generous support of the American people through Cooperative Agreement AID 674-A from the United States Agency for International Development (USAID). The contents are the responsibility of the authors and do not necessarily reflect the views of USAID or the United States Government