Table 2 CHC Trials with PRO Endpoints Search - Clinical Trial Characteristics

Arora et al[33]

- Randomized, open-label, parallel group, controlled trial

CHC patients

- SF-36

-HRQL

Patients with an SVR had better SF-36 and FSS scores than both virological non-responders and patients in the untreated control group at the end of follow-up (week 72; Table 2). In patients who received combination therapy (groups A and B combined), the differences in mean HRQL scores between patients with an SVR and virological non-responders were statistically significant for five of eight SF-36 domains (General Health, P < 0.0001; Bodily Pain Index, P < 0.0001; Role Physical, P < 0.05; Physical Functioning, P < 0.05; Vitality, P < 0.0001) and the Physical Health component score, P < 0.0001 (Table 2). Consistent with these findings, both the FSS Total score (P < 0.01 vs. non-responders) and VAS score (P < 0.01 vs. non-responders) were significantly better in patients with an SVR.

N = 491

- FSS

-Impact and severity of fatigue on HRQL

- Group A = 24 weeks;

Prior therapy: Patients had not received prior treatment for CHC.

Group B = 48 weeks;

No treatment = 72 weeks

-Pegylated interferon alpha 2a + ribavarin

Bernstein et al.[3]

- Open-label RCT

CHC patients

- SF-36

-Physical function, role limitations physical, vitality, general health perceptions, pain, social function, role limitations-emotional, mental health.

(Results using ANCOVA)

-Fatigue

- 72 weeks

N = 676

- FSS

'Virologic response associated with positive HRQL changes in all domains on FSS and SF-36

-Pegylated interferon alpha-2a; unmodified interferon-2a

Prior therapy: none

- Patients taking peginterferon reported better HRQOL and less fatigue than interferon in all FSS domains, and 7/8 of SF-36 domains (exception Physical Function).

Hassanein et al[34]

- Open-label RCT

CHC patients

- SF-36

-Physical function, role limitations physical, vitality, general health perceptions, pain, social function, role limitations-emotional, mental health

(Results using ANCOVA)

- 72 weeks

N = 1121

- FSS

- Using the SF-36, the addition of ribavarin to peginterferon increased HRQOL in domains of physical function, role limitations, vitality, social functioning, mental health (not bodily pain, general health, role limitations emotional).

-Peginterferon alfa-2a +placebo; Peginterferon alfa-2a + ribavarin; Interferon alfa2b + ribavarin

Prior therapy: None

- Using the FSS, the addition of ribavarin to peginterferon increased HRQOL in domains of total fatigue and fatigue severity.

-Fatigue

- Using the SF36, peginterferon (with ribavarin) as compared to interferon (with ribavarin) increased HRQOL in domains of role limitations physical, bodily pain, vitality, social functioning (not physical function, general health, role limitations emotional, and mental health).

- Using the FSS, peginterferon (with ribavarin) as compared to interferon (with ribavarin) increased HRQL in domains total fatigue and fatigue severity.

Nayman Alpat et al.[35]

- Non-randomized trial

CHC patients

- SF-36

-Physical function, role limitations physical, vitality, general health perceptions, pain, social function, role limitations-emotional, mental health

Use of the Mann Whitney U test revealed no significant differences between the treatment groups on any of the domains.

N = 40

- 72 weeks

Prior therapy: Not Reported

-Peginterferon alfa-2a +ribavirin; Peginterferon alfa-2b +ribavirin

Neri et al.[38]

- Randomized, open-label, prospective trial

HCV patients

- HAM-D

Depression

Logistic regression analysis showed in both groups a significant trend from baseline according to the ZSRDS (odds ratio 0.698, p < 0.01 [95% CI 0.59, 0.78]) to predict early major depressive disorders confirmed by the study.

N = 186

- ZSRDS

Prior therapy: Not Reported

- Follow-up once a month for 48 weeks of treatment and 4 and 8 weeks after the end of therapy

- SCID

-Pegylated interferon alpha 2a; Pegylated interferon alpha 2b

Perrillo et al.[37]

- Open-label RCT

CHC patients

- HQLQ

- HQLQ: social function, role limitations emotional, vitality, general mental health, physical function, role limitations physical, freedom from pain, general health, health distress, positive well-being, hepatitis-specific limitations, hepatitis-specific health, PCS, MCS.

ANCOVA was used to test differences in change scores between treatment groups.

- 72 weeks

N = 412

- WPAI

-Peginterferon alfa-2&z.ausco;; Interferon alfa-2b + ribavirin

Prior therapy: None

- HRQL as measured on all domains diminished during treatment for both treatment groups.

- For all SF-36 scales, however, the peginterferon alfa-2a group experienced less impairment than did the interferon alfa-2 b group.

- The between-treatment differences were significant in 3 of the scales at week 48.

-WPAI: impact of therapies on work productivity, health care utilization

Rasenack et al.[36]

- Open-label, randomized, parallel-dose study

CHC patients

- FSS

- HRQL

-FSS- Statistically significant differences between treatment groups favoring peginterferon α-2a were seen in FSS total scores at weeks 2, 12, and 24 and in FSS VAS scores at weeks 2 and 12 (p < 0.01).

N = 531

- SF-36

- Fatigue

Prior therapy: None

- 72 weeks

-SF-36- peginterferon α-2a patients demonstrated significantly better mean scores in all eight SF-36 domains (p < 0.01 to p < 0.05) compared with those treated with unmodified interferon α-2a.

-Peginterferon α-2a (40kD); Unmodified interferon α-2a