Overall Strength of Evidence

Roger Chou; Daniel Hartung; Basmah Rahman; Ngoc Wasson; Erika Cottrell; Rongwei Fu

Appendix GOverall Strength of Evidence

Publication Details

Table

Publication Details

Copyright

Publisher

Agency for Healthcare Research and Quality (US), Rockville (MD)

NLM Citation

Chou R, Hartung D, Rahman B, et al. Treatment for Hepatitis C Virus Infection in Adults [Internet]. Rockville (MD): Agency for Healthcare Research and Quality (US); 2012 Nov. (Comparative Effectiveness Reviews, No. 76.) Appendix G, Overall Strength of Evidence.

Key Question	Number of Studies	Quality (Good, Fair, Poor)	Consistency (High, Moderate, Low)	Directness (Direct or Indirect)	Precision (High, Moderate, Low)	Number of Subjects	Strength of Evidence
1a. What is the comparative effectiveness of antiviral treatment in improving health outcomes in patients with HCV infection?
Long-term clinical outcomes	No studies	No studies	Unknown (no studies)	No studies	No studies	No subjects	Insufficient
Short-term mortality	3 randomized trials	Fair	High	Direct	Low	N = 5,255	Low
Short-term quality of life	1 randomized trial	Fair	Unknown (one study)	Direct	Low	N = 516	Low
1b. How does the comparative effectiveness of antiviral treatment for health outcomes vary according to patient subgroup characteristics, including but not limited to HCV genotype, race, sex, disease severity or genetic markers?
Any clinical outcome	No studies	No studies	No studies	No studies	No studies	No subjects	Insufficient
2a. What is the comparative effectiveness of antiviral treatments in improving intermediate outcomes, such as the rate of viremia, aminotransaminase levels, and histologic changes?
SVR: Dual therapy with pegylated interferon alfa-2a plus ribavirin vs. pegylated interferon alfa-2b plus ribavirin	7 randomized trials	Fair	High	Direct	High	N = 4,660	Moderate
*Duration effects, dual therapy with pegylated interferon plus ribavirin (genotype 2 or 3)*
SVR: 48 vs. 24 weeks	2 randomized trials	Fair	High	Direct	Moderate	N = 609	Moderate
SVR: 24 vs. 12–16 weeks	4 randomized trials	Fair	High	Direct	Moderate	N = 2,599	Moderate
SVR: 24 vs. 12–16 weeks in patients with rapid virological response	3 randomized trials	Fair	High	Direct	Moderate	N = 583	Moderate
*Dose effects, dual therapy with pegylated interferon plus ribavirin (genotype 2 or 3)*
SVR: Lower vs. higher dose pegylated interferon	6 randomized trials	Fair	High	Direct	Moderate	N = 865	Moderate
SVR: Lower vs. higher dose ribavirin	3 randomized trials	Fair	Moderate	Direct	Moderate	N = 2,605	Moderate
SVR: Lower vs. higher dose ribavirin, patients with advanced fibrosis or cirrhosis	1 randomized trial	Fair	Unknown (one study)	Direct	Low	N = 60	Low
*Triple therapy with boceprevir*
SVR: Triple therapy with boceprevir vs. dual therapy	2 randomized trials	Fair	High	Direct	Moderate	N = 1608	Moderate
SVR: Lower vs. higher dose ribavirin	1 randomized trial	Fair	Unknown (one study)	Direct	Low	N = 75	Low
*Triple therapy with telaprevir*
SVR: 24 weeks fixed duration triple therapy with telaprevir vs. 48 weeks dual therapy	3 randomized trials	Fair	High	Direct	Moderate	N= 506	Moderate
SVR: 12 weeks fixed duration triple therapy with telaprevir vs. 48 weeks dual therapy	1 randomized trial	Fair	Unknown (one study)	Direct	Low	N = 209	Low
SVR: 48 weeks fixed duration triple therapy with telaprevir vs. 24 weeks triple therapy	1 randomized trial	Fair	Unknown (one study)	Direct	Low	N = 189	Low
SVR: Response-guided triple therapy with telaprevir vs. dual therapy	1 randomized trial	Fair	Unknown (one study)	Direct	Low	N = 1,088	Low
SVR: Triple therapy with telaprevir, lower versus higher telaprevir dose and pegylated interferon alfa-2a vs. alfa-2b	1 randomized trial	Fair	Unknown (one study)	Direct	Low	N = 161	Low
SVR: 48 vs. 24 weeks in patients with an extended rapid virological response	1 randomized trial	Fair	Unknown (one study)	Direct	Low	N = 540	Low
2b. How does the comparative effectiveness of antiviral treatment for intermediate outcomes vary according to patient subgroup characteristics, including but not limited to HCV genotype, race, sex, disease severity or genetic markers?
SVR: Dual therapy with pegylated interferon alfa-2a plus ribavirin vs. dual therapy with pegylated interferon alfa-2b plus ribavirin: effects of race, sex, age, baseline fibrosis stage, or baseline viral load	1 randomized trial	Fair	Unknown (one study)	Direct	Moderate	N = 3070	Low
SVR: Dual therapy with pegylated interferon alfa-2a plus ribavirin vs. dual therapy with pegylated interferon alfa-2b plus ribavirin: effects of genotype	4 randomized trials	Fair	High	Direct	High	N = 1,152	Moderate
SVR: Triple therapy with boceprevir vs. dual therapy: effects of sex and race	2 randomized trials	Fair	High	Direct	Moderate	N = 1,617	Moderate
SVR: Triple therapy with boceprevir vs. dual therapy: effects of baseline viral load	2 randomized trials	Fair	High	Direct	Moderate	N = 1,617	Moderate
SVR: Triple therapy with telaprevir vs. dual therapy: effects of age, sex, race, baseline fibrosis, and body weight	1 randomized trial	Fair	Unknown (1 study)	Direct	Moderate	N = 1,088	Moderate (for age and sex) to low (for other factors)
SVR: Triple therapy with telaprevir vs. dual therapy: effects of baseline viral load	2 randomized trials	Fair	Low	Direct	Moderate	N = 729	Insufficient
3a. What are the comparative harms (including intolerance to treatment) associated with antiviral treatment?
Harms: Dual therapy with pegylated interferon alfa-2b plus ribavirin vs. pegylated interferon alfa-2a plus ribavirin	5 randomized trials, depending on specific harm	Fair	High	Direct	Moderate	N = 4,047	Moderate
Harms: Triple therapy with boceprevir	2 randomized trials	Fair	High	Direct	Moderate	N = 3,501	Moderate
Harms: 24 weeks fixed duration triple therapy with telaprevir vs. 48 weeks dual therapy	3 randomized trials	Fair	High	Direct	Moderate	N = 3,591	Moderate
Harms: 12 weeks fixed duration triple therapy with telaprevir vs. 48 weeks dual therapy	2 randomized trials	Fair	High	Direct	Moderate	N = 573	Moderate
Harms: Response-guided triple therapy with telaprevir vs. dual therapy	1 randomized trial	Fair	Unknown (one study)	Direct	Low	N = 189	Low
3b. Do these harms differ according to patient subgroup characteristics, including HCV genotype, race, sex, disease severity or genetic markers?
Dual therapy with pegylated interferon alfa-2b plus ribavirin vs. pegylated interferon alfa-2a plus ribavirin	3 randomized trials	Fair	High	Indirect (no study stratified harms by patient subgroups, 3 trials evaluated only genotype 1 patients)	Moderate	N = 3,305	Insufficient
Triple therapy with pegylated interferon, ribavirin, and telaprevir or boceprevir	No studies	No studies	Unknown (no studies)	No studies	No studies	No subjects	Insufficient
4. Have improvements in intermediate outcomes (viremia, liver function tests, histologic changes) been shown to reduce the risk or rates of health outcomes from HCV infection?
Mortality and long-term hepatic complications	19 cohort studies	Fair	High	Direct	High	N = 27,992	Moderate
Short-term quality of life	9 cohort studies	Poor	High	Direct	High	N = 4,981	Low

: Note: HCV=hepatitis C virus, SVR=sustained virologic response.