Review for 10.1186/1471-230X-14-137 (2014)

Reviewer's report
Title:Modelling the impact of improving screening and treatment of chronic
hepatitis C virus infection on future hepatocellular carcinoma rates and
liver-related mortality
Version:2Date:21 May 2014
Reviewer: Ashish Aggarwal
Reviewer's report:
Reviewer Comments
This interesting study by Cramp et al aimed to estimate the future burden of
Hepatitis C virus (HCV)-related disease in England if current management
strategies remain the same and the likely impact as new therapies become
available. Adapting a previously published model, authors compared the
“Base-case scenario” model based upon current management strategies to the
“increasing diagnosis and treatment or the best case” model that accounted for
the new therapies as they become available. Authors estimated that compared to
the “base case” projections, , increasing treatment numbers by 115% by 2018
would significantly reduce HCV- related hepatic disease and mortality. While this
is an interesting, with reassuring results, we would like the authors to consider
following suggestions.
Major points
1. The introduction and results sections are well written, whereas Methodology
section and Discussion sections need to be refined. In Methodology section,
authors should consider adding more details about the model such as - how was
the historical data extrapolated to make future assumptions, whether these
involve patients listed for transplant/ transplanted, how were the costs calculated,
if sensitivity analyses was done to identify uncertainties etc. Does this model
assume that all the patients are treatment naïve?
2. In Methodology, please clarify if the dataset used to derive ‘base-case’
scenario reflects mostly patients treated with ribavirin and peg-IFN or do these
also include patients treated with protease inhibitors like boceprevir/ telaprevir
which have been approved for more than 2 years or even newer medications like
sofosbuvir etc. If yes, then what modifications were made to adjust for the
different treatment modalities and their potential impact on future predictions? If
the ‘base case’ involves only the patients treated with ribavirin and peg-IFN, then
do you think the ‘base case’ reflects an outdated treatment regimen as opposed
to the ‘current treatment strategies’
3. Was the model tested to back calculate the expected prevalence of Hepatitis
C, including the development of HCC or decompensated liver disease, mortality
using the historical data and then compared with the actual data to see if the
predictions are close to the actual data? Is it possible to do this testing?
4. In Methodology, under “Increasing diagnosis and treatment of HCV”, the
model assumed that the number of patients treated increased from 5,430 in 2013
to
8,150 in 2014 and then to 11710 in 2018. What was the basis of this
assumption?
5. In Results Section, Please include the respective data for historical cohort for
HCV related morbidity and mortality in Table 3 for easier readability and
comparison
6. While it is certainly plausible and very likely that with Hepatitis C eradication,
the rate of progression of liver disease will perhaps be slower. However, data is
scant for patients who had already developed advanced fibrosis or cirrhosis and
then undergo HCV treatment. In addition, it is not entirely known how HCV
treatment changes the risk of HCC development in an already cirrhotic patient.
This should perhaps be discussed in the Discussion/ Limitation section or an
appropriate reference should be included that made the basis for calculation of
reduction of HCV related morbidity/ mortality in ‘best case’ strategy
7. The authors very cursorily address the cost effectiveness with the new
strategy. Further details should be given regarding the methodology behind cost
estimations? If the primary aim is to see if the new treatments will be cost
effective, then a detailed analysis should be included in the results including the
current healthcare costs, main factors responsible for the cost including cost of
treatment of HCV, cirrhosis related complications or HCV in addition to projected
costs with base case strategy.
8. This section of Discussion on overcoming barriers to care can be curtailed as it
does not add significantly to the strengths/ findings of the study. Neither is this
the main focus or aim of the study. and goes beyond the scope of data
presented. Authors should consider condensing the last 2 paragraphs in the
Discussion section. In addition, since the analyses for cost effectiveness is
incomplete without adjusting for the treatment costs, as the authors have
correctly identified, discussion regarding cost effective strategies for reducing
HCV-related morbidity and mortality should be curtailed.
Minor points
1. There is data that genotype 3 incidence is rising in UK and genotype 1 is
declining. Do you anticipate any major changes to your analysis based upon that
or do you anticipate that there won’t be any significant changes? (Ref: Costella,
Annastella and Health Protection Agency United Kingdom. Hepatitis C in the UK
2008. The Health Protection Agency Annual Report. Health Protection Agency
Centre for Infections, London, 2008)
2. “The model estimates that 5,430 HCV patients were treated in England during
2010,
based on the number of standard units of peg-IFN sold (IMS Health Incorporated;
Danbury, Connecticut”. Does this reliably capture nationwide peg-IFN sale?
3. Page 13, Line 353, 2013 and 49,730 need to be separated
Level of interest: An article whose findings are important to those with closely
related research interests
Quality of written English: Acceptable
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