Evaluation of health-related quality of life in hemolytic uraemic syndrome patients treated with eculizumab: a systematic evaluation on basis of EMPRO

Figures & data

Figure 1. PRISMA flow diagram depicting the selection of studies for systematic review.

Table 1. Characteristics of included studies (n = 10).

Sl. No.	Author, year of publication, country and r number eference	Study characteristics		Characteristics of participants		HRQOL Questionnaire	Results	p-value
		Design	Study period (weeks)	Sample size	Mean/median age, years (SD)
1.	Saultz et al. (2015), USA [40]	P	52	1026	51 (range 19– 69)	HIT- 6	No significant difference in the HIT-6 scores of aHUS patients	–
2.	Muus et al. (2011), Multinational [41]	P, O, S, M, P-2	104	37	28	EQ-5D, VAS	ECU significantly improved the HRQoL in aHUS patients	.002
3.	Licht et al. (2012), Multinational [42]	P, O, S, M, P-2	104	20	28 (range 13–63)	EQ-5D	ECU significantly improved the HRQoL in aHUS patients	<.001
4.	Legendre et al. (2013), Multinational [27]	P, O, S, M, P-2	52	37	28 (range 13–63)	EQ-5D, VAS	ECU significantly improved the HRQoL in aHUS patients	<.001
5.	Licht et al. (2015), Multinational [29]	P, O, S, M, P-2	104	37	28 (range 13–63)	EQ-5D	ECU significantly improved the HRQoL in aHUS patients	<.05
6.	Greenbaum et al. (2014), Multinational [43]	P, O, S, M, P-2	52	22	6.6 (6.1)	FACIT-F	ECU significantly improved the HRQoL in aHUS patients	.0001
7.	Greenbaum et al. (2016), Multinational [28]	P, O, S, M, P-2	26	22	6.5 (0.4–17)	FACIT-F	The 26 weeks of ECU therapy significantly improved the HRQoL in aHUS patients	<.0001
8.	Greenbaum et al. (2012), Multinational [44]	P, O, S, M, P-2	104	17	28 (range 17–68)	EQ-5D	ECU significantly improved the HRQoL in aHUS patients	.0001
9.	Loirat et al. (2011), Multinational [45]	P, O, S, M, P-2	104	17	28 (range 17–68)	EQ-5D	ECU significantly improved the HRQoL in aHUS patients	.0001
10.	Fakhouri et al. (2016), Multinational [46]	P, O, S, M, P-2	26	44	40 (range 18–80)	EQ-5D, FACIT-F and SF-36	ECU significantly improved the HRQoL in aHUS patients	.001

P: prospective; O: open-label; S: single-arm; M: multicenter; P-2: phase 2 trials; EQ-5 D: EuroQol five dimensions questionnaire; FACIT-F: Functional Assessment of Chronic Illness Therapy-Fatigue; SF-36: 36-item Short Form Health Survey; HIT- 6: Headache Impact Test-6; VAS: Visual Analogue Scale; ECU: eculizumab; aHUS: atypical hemolytic-uremic syndrome; HRQoL: Health-Related Quality of Life.

Figure 2. Risk of bias graph of included trials: Review authors’ judgments about each risk of bias item for each included study (A) and each risk of bias item presented as percentages across all included studies (B).

Table 2. Review of the quality of studies determined using downs and black scoring system.

Sl. No.	Author	Reporting (Max: 11)	External validity (Max: 3)	Internal validity-bias (Max: 7)	Internal validity -confounding (selection bias) (Max: 6)	Total (27)
1.	Saultz et al. (2015), USA [40]	5	3	1	0	9
2.	Muus et al. (2011), Multinational [41]	11	3	4	2	20
3.	Licht et al. (2012), Multinational [41]	11	3	4	2	20
4.	Legendre et al. (2013), Multinational [27]	11	3	4	2	20
5.	Licht et al., (2015), Multinational [29]	11	3	4	2	20
6.	Greenbaum et al. (2014), Multinational [43]	11	3	3	1	18
7.	Greenbaum et al. (2016), Multinational [28]	11	3	3	1	18
8.	Greenbaum et al. (2012), Multinational [44]	10	3	3	0	16
9.	Loirat et al. (2011), Multinational [45]	10	3	3	0	16
10.	Fakhouri et al. (2016), Multinational [46]	11	3	4	2	20

Figure 3. Results of the systematic literature review. Number of manuscripts identified and used in the EMPRO evaluation.

Figure 4. Overall ranking of instruments and their attribute-specific EMPRO scores. EMPRO scores ranged 0–100 (worst to best). EMPRO: Evaluating Measures of Patient-Reported Outcomes; EQ-5D: EuroQol five dimensions questionnaire; FACIT-F: Functional Assessment of Chronic Illness Therapy-Fatigue; SF-36: 36-item Short Form Health Survey; HIT- 6: Headache Impact Test-6; VAS: Visual Analogue Scale.

Table 3. Ratings of each EMPRO item and attribute for every quality of life instrument identified.

Attributes	HIT- 6^a	EQ-5D^a	VAS^a	FACIT-F^a	SF-36^a
Conceptual and measurement model	52.38	85.71	80.95	42.86	71.43
Concept of measurement stated	++++	++++	++++	++++	++++
Obtaining and combining items described	++++	++++	++++	++	++++
Rationality for dimensionality and scales	+	++++	++++	+	++++
Involvement of target population	++++	++++	—	+++	—
Scale variability described and adequate	+	+++	++++	++	+++
Level of measurement described	+	++++	+++	+	+++
Procedures for deriving scores	++++	+++	++++	+++	++++
Reliability	62.50	62.50	66.67	25.00	66.67
Data collection methods described	++++	++++	++++	++	++++
Cronbach’s alpha adequate	+	+	++++	++	+++
Item Response Theory (IRT) estimates provided	+++	++++	—	—	—
Testing in different populations	++++	—	—	—	++++
Data collection methods described	+++	++++	+++	++	++++
Test–retest and time interval adequate	+++	+++	+++	++	+++
Reproducibility coefficients adequate	+	++	++	++	++
IRT estimates provided	+++	+++	+++	—	—
Validity	44.44	63.89	83.33	54.17	76.67
Content validity adequate	+	++	++++	+++	+
Construct/criterion validity adequate	++++	++++	++++	+++	++++
Sample composition described	++++	++	++++	++	++++
Prior hypothesis stated	+	++	+++	+++	+++
Rational for criterion validity	+	+++	N/A	N/A	N/A
Tested in different populations	++++	++++	N/A	N/A	++++
Responsiveness	66.67	100.00	77.78	55.56	55.56
Adequacy of methods	++++	++++	++++	+++	+++
Description of estimated magnitude of change	+++	++++	++++	+++	+++
Comparison of stable and unstable groups	++	++++	++	++	++
Interpretability	77.78	61.11	66.67	77.78	44.44
Rational of external criteria	+++	++++	++++	+++	+++
Description of interpretation strategies	++++	++	+++	++++	+++
How data should be reported stated	+++	++	++	++++	+
Burden	45.24	54.76	59.52	23.81	42.86
Skills and time needed	+++	+++	+++	++	+
Impact on respondents	+++	+++	++	++	++++
Not suitable circumstances	+++	++++	+	++	+
Resources required	+++	+++	+++	+++	++++
Time required	—	—	+++	—	—
Training and expertise needed	—	—	++++	—	—
Burden of score calculation	++	++++	++++	+	++++
Alternative modes of administration	—	75.00	—	16.67	41.67
Metric characteristics of alternative forms	—	+++	—	+	++
Comparability of alternative forms	—	+++	—	++	+++
Cultural and language adaptations or translations	—	100.00	100.00	27.78	83.33
Linguistic equivalence	—	++++	++++	++	++++
Conceptual equivalence	—	++++	++++	++	++++
Significant differences	—	++++	++++	+	+++
Global score (Panoramic)	59.09	73.81	73.83	50.24	61.70
Global score (Version Specific)	—	78.17	78.19	47.42	65.31

^a ++++: 4 (strongly agree); +++: 3; ++: 2; +: 1 (strongly disagree), —: no information, N/A: Not Applicable. The higher the agreement the better the rating. EQ-5D: EuroQol five dimensions questionnaire; FACIT-F: Functional Assessment of Chronic Illness Therapy-Fatigue; SF-36: 36-item Short Form Health Survey; HIT-6: Headache Impact Test-6; VAS: Visual Analogue Scale.

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