Reviewer's report
Title:Excellent superiority and specificity of COBAS TaqMan HCV assay in an
early viral kinetic change during pegylated interferon-alpha 2b plus ribavirin
treatment
Version: 1Date:27 October 2008
Reviewer: Chia-Yen L Dai
Reviewer's report:
Ogawa et al. conducted their study enrolling 80 HCV genotype 1 patients (39
SVR and 41non-SVR patients) with a complete 48-week treatment of PEG-IFN
alpha-2b
plus RBV to analyze the possible association between sustained virological
response and EVR by comparing TaqMan with Amplicor assays. Authors
concluded that the COBAS TaqMan HCV assay is very useful for monitoring
HCV viremia during antiviral treatment to predict a SVR in HCV genotype 1
patients. The study focused on the hot topic of the on-treatment viral kinetics and
the association with treatment response. Also the comparison between TaqMan
assay with Amplicor 10-fold method assay is quite unique although Amplicor
10-fold method assay may not a standard method as other assays such as
branched DNA assay.Some issues should be notified.
Major Compulsory Revisions
1. In addition to EVR, the critical role of rapid virological response (RVR) on the
SVR of CHC patients with genotype 1 and non-1 infection has been recently
emphasized. Authors have already evaluated the result of HCV RNA at week 4
but did not mention this concept. I strongly recommend authors to discuss this
point deeply which can strengthen the results and the value of this study.
2. In evaluation of the pretreatment predictors of SVR for combination therapy in
genotype 1 chronic hepatitis C patients, the baseline viral load has been
recognized as one of the important factors. Authors have to analyze the influence
of pretreatment HCV RNA levels by TaqMan assay on the efficacy of therapy in
Table 1. The multivariate analyses also have to be used.
3. The comparison of pretreatment viral load between TaqMan assay and
Amplicor 10-fold method assay is interesting and suggested to be described in
detail. Authors observed a significant positive correlation between these two
assays (r= 0.849, P<0.0001) but however concluded the different roles on the
predicting SVR. What is the explanation? Is there possible an difference of
correlation between high and low viral load (speculating from Figure 1)? The
quantification results of Amplicor 10-fold method assay seemed lower than
TaqMan assay. Authors are encouraged to compare the difference to
quantification results between these two assays.
4. The shown data and legends for Figure 3 and 4 are insufficient. For example,
the case numbers for Figure 3 have to be shown. Authors claimed “in non-SVR
patients, significant differences in the undetectable HCV RNA rate by TaqMan (at
weeks 2, 4, 8, and 12, 0%, 0%, 0%, and 58.5%, respectively) and qualitative
Amplicor (at weeks 2, 4, 8, and 12, 2.4%, 12.2%, 34.1%, and 100%, respectively)
were found”. What are the p values of the statistical analyses? The EVR rate was
100% by qualitative Amplicor assay (detection limit 50 IU/mL) in these genotype
1 patients and can authors explain why the EVR rate is so high? The Figure 4
showed the PPV only. The sensitivity, specificity, negative predictive value and
accuracy are suggested to be presented. Also the numbers in Figure 4 have to
be explained more.
Minor Essential Revisions
1. The Amplicor 10-fold method has a lower limit of quantitation of 5000 IU (5
kIU/mL). Authors transformed the level into the logarithmic level (1.7 log IU/mL?)
on page 8 and this is a mistake. Please revise.
2. It is not adequate to list the HCV genotype 1 in Table 1.
3. The legend of Figure 1 has to address the important results for readers of
correlation of pretreatment hepatitis C virus (HCV) RNA levels between TaqMan
and Amplicor 10-fold method assays.
4. The sentence of page 13 para 2 “ In the present study………on the real-time
PCR technology” is confusing which should be revised.
Discretionary Revisions
1. The English can be improved by a native speaker.
Level of interest: An article whose findings are important to those with closely
related research interests
Quality of written English: Needs some language corrections before being
published
Statistical review: Yes, but I do not feel adequately qualified to assess the
statistics.
Declaration of competing interests:
I declare that I have no competing interests.
Reviewer's report
Title:Excellent superiority and specificity of COBAS TaqMan HCV assay in an
early viral kinetic change during pegylated interferon-alpha 2b plus ribavirin
treatment
Version: 1Date:27 October 2008
Reviewer: Chia-Yen L Dai
Reviewer's report:
Ogawa et al. conducted their study enrolling 80 HCV genotype 1 patients (39
SVR and 41non-SVR patients) with a complete 48-week treatment of PEG-IFN
alpha-2b
plus RBV to analyze the possible association between sustained virological
response and EVR by comparing TaqMan with Amplicor assays. Authors
concluded that the COBAS TaqMan HCV assay is very useful for monitoring
HCV viremia during antiviral treatment to predict a SVR in HCV genotype 1
patients. The study focused on the hot topic of the on-treatment viral kinetics and
the association with treatment response. Also the comparison between TaqMan
assay with Amplicor 10-fold method assay is quite unique although Amplicor
10-fold method assay may not a standard method as other assays such as
branched DNA assay.Some issues should be notified.
Major Compulsory Revisions
1. In addition to EVR, the critical role of rapid virological response (RVR) on the
SVR of CHC patients with genotype 1 and non-1 infection has been recently
emphasized. Authors have already evaluated the result of HCV RNA at week 4
but did not mention this concept. I strongly recommend authors to discuss this
point deeply which can strengthen the results and the value of this study.
2. In evaluation of the pretreatment predictors of SVR for combination therapy in
genotype 1 chronic hepatitis C patients, the baseline viral load has been
recognized as one of the important factors. Authors have to analyze the influence
of pretreatment HCV RNA levels by TaqMan assay on the efficacy of therapy in
Table 1. The multivariate analyses also have to be used.
3. The comparison of pretreatment viral load between TaqMan assay and
Amplicor 10-fold method assay is interesting and suggested to be described in
detail. Authors observed a significant positive correlation between these two
assays (r= 0.849, P<0.0001) but however concluded the different roles on the
predicting SVR. What is the explanation? Is there possible an difference of
correlation between high and low viral load (speculating from Figure 1)? The
quantification results of Amplicor 10-fold method assay seemed lower than
TaqMan assay. Authors are encouraged to compare the difference to
quantification results between these two assays.
4. The shown data and legends for Figure 3 and 4 are insufficient. For example,
the case numbers for Figure 3 have to be shown. Authors claimed “in non-SVR
patients, significant differences in the undetectable HCV RNA rate by TaqMan (at
weeks 2, 4, 8, and 12, 0%, 0%, 0%, and 58.5%, respectively) and qualitative
Amplicor (at weeks 2, 4, 8, and 12, 2.4%, 12.2%, 34.1%, and 100%, respectively)
were found”. What are the p values of the statistical analyses? The EVR rate was
100% by qualitative Amplicor assay (detection limit 50 IU/mL) in these genotype
1 patients and can authors explain why the EVR rate is so high? The Figure 4
showed the PPV only. The sensitivity, specificity, negative predictive value and
accuracy are suggested to be presented. Also the numbers in Figure 4 have to
be explained more.
Minor Essential Revisions
1. The Amplicor 10-fold method has a lower limit of quantitation of 5000 IU (5
kIU/mL). Authors transformed the level into the logarithmic level (1.7 log IU/mL?)
on page 8 and this is a mistake. Please revise.
2. It is not adequate to list the HCV genotype 1 in Table 1.
3. The legend of Figure 1 has to address the important results for readers of
correlation of pretreatment hepatitis C virus (HCV) RNA levels between TaqMan
and Amplicor 10-fold method assays.
4. The sentence of page 13 para 2 “ In the present study………on the real-time
PCR technology” is confusing which should be revised.
Discretionary Revisions
1. The English can be improved by a native speaker.
Level of interest: An article whose findings are important to those with closely
related research interests
Quality of written English: Needs some language corrections before being
published
Statistical review: Yes, but I do not feel adequately qualified to assess the
statistics.
Declaration of competing interests:
I declare that I have no competing interests.
Please review this paper.
user
Reviewer's report
Title:Excellent superiority and specificity of COBAS TaqMan HCV assay in an
early viral kinetic change during pegylated interferon-alpha 2b plus ribavirin
treatment
Version: 1Date:27 October 2008
Reviewer: Chia-Yen L Dai
Reviewer's report:
Ogawa et al. conducted their study enrolling 80 HCV genotype 1 patients (39
SVR and 41non-SVR patients) with a complete 48-week treatment of PEG-IFN
alpha-2b
plus RBV to analyze the possible association between sustained virological
response and EVR by comparing TaqMan with Amplicor assays. Authors
concluded that the COBAS TaqMan HCV assay is very useful for monitoring
HCV viremia during antiviral treatment to predict a SVR in HCV genotype 1
patients. The study focused on the hot topic of the on-treatment viral kinetics and
the association with treatment response. Also the comparison between TaqMan
assay with Amplicor 10-fold method assay is quite unique although Amplicor
10-fold method assay may not a standard method as other assays such as
branched DNA assay.Some issues should be notified.
Major Compulsory Revisions
1. In addition to EVR, the critical role of rapid virological response (RVR) on the
SVR of CHC patients with genotype 1 and non-1 infection has been recently
emphasized. Authors have already evaluated the result of HCV RNA at week 4
but did not mention this concept. I strongly recommend authors to discuss this
point deeply which can strengthen the results and the value of this study.
2. In evaluation of the pretreatment predictors of SVR for combination therapy in
genotype 1 chronic hepatitis C patients, the baseline viral load has been
recognized as one of the important factors. Authors have to analyze the influence
of pretreatment HCV RNA levels by TaqMan assay on the efficacy of therapy in
Table 1. The multivariate analyses also have to be used.
3. The comparison of pretreatment viral load between TaqMan assay and
Amplicor 10-fold method assay is interesting and suggested to be described in
detail. Authors observed a significant positive correlation between these two
assays (r= 0.849, P<0.0001) but however concluded the different roles on the
predicting SVR. What is the explanation? Is there possible an difference of
correlation between high and low viral load (speculating from Figure 1)? The
quantification results of Amplicor 10-fold method assay seemed lower than
TaqMan assay. Authors are encouraged to compare the difference to
quantification results between these two assays.
4. The shown data and legends for Figure 3 and 4 are insufficient. For example,
the case numbers for Figure 3 have to be shown. Authors claimed “in non-SVR
patients, significant differences in the undetectable HCV RNA rate by TaqMan (at
weeks 2, 4, 8, and 12, 0%, 0%, 0%, and 58.5%, respectively) and qualitative
Amplicor (at weeks 2, 4, 8, and 12, 2.4%, 12.2%, 34.1%, and 100%, respectively)
were found”. What are the p values of the statistical analyses? The EVR rate was
100% by qualitative Amplicor assay (detection limit 50 IU/mL) in these genotype
1 patients and can authors explain why the EVR rate is so high? The Figure 4
showed the PPV only. The sensitivity, specificity, negative predictive value and
accuracy are suggested to be presented. Also the numbers in Figure 4 have to
be explained more.
Minor Essential Revisions
1. The Amplicor 10-fold method has a lower limit of quantitation of 5000 IU (5
kIU/mL). Authors transformed the level into the logarithmic level (1.7 log IU/mL?)
on page 8 and this is a mistake. Please revise.
2. It is not adequate to list the HCV genotype 1 in Table 1.
3. The legend of Figure 1 has to address the important results for readers of
correlation of pretreatment hepatitis C virus (HCV) RNA levels between TaqMan
and Amplicor 10-fold method assays.
4. The sentence of page 13 para 2 “ In the present study………on the real-time
PCR technology” is confusing which should be revised.
Discretionary Revisions
1. The English can be improved by a native speaker.
Level of interest: An article whose findings are important to those with closely
related research interests
Quality of written English: Needs some language corrections before being
published
Statistical review: Yes, but I do not feel adequately qualified to assess the
statistics.
Declaration of competing interests:
I declare that I have no competing interests.
assistant