Mangia 2008.

Methods	Randomised clinical trial. Study design: Chronic HCV G1 patients were randomised to receive therapy for 48 weeks (standard group) or for an individualized duration, based on the time when HCV RNA first became undetectable (variable group). In the variable group, patients who were first HCV‐RNA negative at week 4 were treated for a total of 24 weeks (not included in this meta‐analysis), whereas those who were first HCV‐RNA negative at weeks 8 and 12 were treated for a total of 48 and 72 weeks, respectively (not included as well). Patients with a 2 log drop in HCV RNA levels at week 12 were treated for 48 and 72 weeks in the standard or variable group, respectively. All patients viraemic at week 24 were considered nonresponders and excluded from further treatment. Duration of follow‐up: 24 weeks after the end of treatment.
Participants	Location: 11 centres in the south of Italy. Time of participant selection: 6/2004 to 12/2005. Included participants in our meta analysis: chronic hepatitis C genotype 1 naive patients with detectable HCV‐RNA and ≥ 2 log viral reduction at week 12 and undetectable HCV RNA at week 24. No. participants: 21 in the 48‐week treatment group and 53 in the 72‐week treatment group. Mean age: no data. Males: no data. Mean BMI: no data. Liver biopsy: was not mandatory for the patients to be enrolled.
Interventions	Experimental: s.c. peginterferon alfa‐2a 180 mcg/week or s.c. peginterferon alfa‐2b 1.5 µg/kg/week and p.o. ribavirin 1000/1200 mg*1/d (weight dependent) for individualised duration (variable group). In the trial, the variable group treatment's duration periods were 24, 48, and 72 weeks for HCV‐RNA negative at week 4, 8, and 12 participants, respectively. Slow responders, defined as patients with detectable HCV RNA and ≥ 2 log viral reduction at week 12 and undetectable HCV RNA at week 24 were treated for 72 weeks and were included in our meta‐analysis. Control: s.c. peginterferon alfa‐2a 180 µg/week or s.c. peginterferon alfa‐2b 1.5 µg/kg/week and p.o. ribavirin 1000/1200 mg*1/d (weight depended) for 48 weeks.
Outcomes	Outcomes and time points considered in the review: Primary outcome: SVR. Secondary outcomes: treatment failures: relapse, nonresponse, discontinuation. Outcomes and time points not considered in the review: ascertaining SVR according to on‐treatment virologic response as determined by qualitative HCV RNA assays at weeks 4, 8, and 12 and comparison of these rates in the standard and variable groups; evaluation of predictors of 12‐week virologic response and SVR‐associated parameters: age, gender, body weight, BMI, serum alanine transferase level, serum HCV RNA level, HCV genotype, stage of fibrosis and grade of inflammation.
Notes	A total of 696 naive patients with chronic HCV genotype 1 were enrolled. The standard group included 237 participants : 62 had RVR (HCV RNA negative at week 4), 64 were HCV‐RNA negative at week 8, 21 were HCV‐RNA negative at week 12 and 21 were slow responders based on HCV RNA results at week 12 and 24. 69 participants had less than 2 log viral reduction at week 12 and therefore treatment was discontinued. The variable group included 459 patients: 123 were RVR, 128 were HCV‐RNA negative at week 8, 52 were HCV‐RNA negative at week 12 and 53 were slow responders. 103 participants had less than 2 log viral reduction at week 12 and with discontinuation of treatment .
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	"A computer‐generated list of randomisation was sent to each participating center, where, at the study entry, patients were allocated 1:2 to the standard or variable groups in blocks of five."
Allocation concealment (selection bias)	Unclear risk	Participants were allocated in blocks of five, therefore investigators could predict allocation for some of the participants.
Blinding (performance bias and detection bias) All outcomes	High risk	There was no blinding.
Incomplete outcome data (attrition bias) All outcomes	High risk	There were not available data about number of slow responders that completed therapy, about the number of slow responders that treatment reduction was needed or therapy was discontinued due to adverse events, and about the rate of serious adverse events in slow responders.
Selective reporting (reporting bias)	High risk	No clinical data on mortality were reported.
Other bias	Low risk	The trial appears to be free of other sources of bias.