The Hep-CORE policy score: A European hepatitis C national policy implementation ranking based on patient organization data.

BACKGROUND: New hepatitis C virus (HCV) treatments spurred the World Health Organization (WHO) in 2016 to adopt a strategy to eliminate HCV as a public health threat by 2030. To achieve this, key policies must be implemented. In the absence of monitoring mechanisms, this study aims to assess the extent of policy implementation from the perspective of liver patient groups.
METHODS: Thirty liver patient organisations, each representing a country, were surveyed in October 2018 to assess implementation of HCV policies in practice. Respondents received two sets of questions based on: 1) WHO recommendations; and 2) validated data sources verifying an existing policy in their country. Academic experts selected key variables from each set for inclusion into policy scores. The similarity scores were calculated for each set with a multiple joint correspondence analysis. Proxy reference countries were included as the baseline to contextualize results. We extracted scores for each country and standardized them from 0 to 10 (best).
RESULTS: Twenty-five countries responded. For the score based on WHO recommendations, Bulgaria had the lowest score whereas five countries (Cyprus, Netherlands, Portugal, Slovenia, and Sweden) had the highest scores. For the verified policy score, a two-dimensional solution was identified; first dimension scores pertained to whether verified policies were in place and second dimension scores pertained to the proportion of verified policies in-place that were implemented. Spain, UK, and Sweden had high scores for both dimensions.
CONCLUSIONS: Patient groups reported that the European region is not on track to meet WHO 2030 HCV goals. More action should be taken to implement and monitor HCV policies.

Introduction

Viral hepatitis is one of the leading causes of death and disability worldwide and, since 2013, has surpassed HIV/AIDS and malaria in terms of annual deaths. An estimated 71 million people worldwide live with chronic hepatitis C virus (HCV) infection, including 5.6 million people in the World Health Organization (WHO) European Region [1]. The largest burden of HCV-related mortality is caused by liver cirrhosis and liver cancer [2]. In Europe, the populations most impacted are people who are incarcerated, people living with HIV (PLHIV) men who have sex with men (MSM), and people who inject drugs (PWID) [3]. According to the European Centre for Disease Prevention and Control (ECDC), in the European Union (EU)/ European Economic Area (EEA), 45.5% of new cases of hepatitis C with transmission information were attributed to injection drug use [4].

In 2016, WHO set the ambitious goal of eliminating hepatitis B and C as a public health threat by 2030 in its first viral hepatitis global health sector strategy (GHSS) [5]. Elimination of viral hepatitis is defined as a 65% reduction in mortality and a 90% (80% for HCV) reduction in the incidence of viral hepatitis [5]. This goal was soon followed by further specified targets in the WHO European Region’s Action plan for the health sector response to viral hepatitis [6]. Despite these commitments, many countries have been slow to implement policies to achieve elimination targets.

Prior to the GHSS, two global viral hepatitis policy monitoring studies were conducted and highlighted the importance of addressing the viral hepatitis epidemic. These studies were inspired by the absence of a European or global framework to monitor viral hepatitis policy and the increasing availability of all-oral, highly effective direct acting antivirals (DAAs) [7, 8]. To advance necessary civil society engagement and to fill the knowledge gap surrounding policy, the European Liver Patients’ Association (ELPA) commissioned the Hep-CORE study in 2015 as a longitudinal project to monitor viral hepatitis policies in countries where they had member patient organizations. The Hep-CORE study works with patient groups to monitor policy implementation, traditionally the role of governments and global bodies. A notable exception to this is the community response to HIV, with civil society organizations, including patient groups, playing a pivotal role in the Global AIDS Response Progress Reporting. This has strengthened formal and informal monitoring functions, which has provided an inclusive perspective to compare data against reports issued by governments to global governance bodies, including WHO and UNAIDS [9]. Notably, civil society, and HIV community activism and involvement specifically, have improved policy monitoring, highlighted the needs of marginalized groups, and fostered effective government and civil society collaboration [10].

In its first two years, Hep-CORE focused on patient group reporting on the existence of viral hepatitis policies in their country. Results at baseline (2016) showed that there were few policies supporting viral hepatitis policy recommendations, and, in 2017, only 52% of European countries had a national viral hepatitis plan or strategy in place [11-13]. In 2018, the Lancet Gastroenterology Hepatology Commission called for measuring national responses to viral hepatitis to ascertain a country’s progress towards its elimination [14]. Inspired by this call, Hep-CORE 2018 set out to assess whether known national HCV policies in Europe, the United Kingdom (UK), and the Mediterranean Basin are functioning in practice and to score the extent of implementation according to patient advocacy groups.

Methods

Data collection

Participants were recruited through a purposive sampling process. We emailed an invitation to participate in the survey to one liver patient group in each of the countries where ELPA had members at the time of 2018 study recruitment. In countries with more than one patient group, we selected the group that was most involved in viral hepatitis advocacy in collaboration with the President of ELPA. A random sample of participants was not possible as the number of potential participants per country was often one and at most three. We invited the participants to complete the survey online using a customised survey link auto-generated by the Research Electronic Data Capture (REDCap) system, hosted online by Rigshospitalet, University of Copenhagen, Denmark, and distributed to each individual via email. Data were collected in September–October 2018. After data collection, we reviewed data and queried study participants via email about incomplete, inconsistent, or unclear information. Demographics and specific detail of who responded were collected, but are not disclosed to protect the anonymity of the respondents.

The survey questions were closed‐ended and used a 5-point Likert scale [15]. A free-text box was available for participants to further comment on their responses. Additionally, to assess the base knowledge of the study participants, a 4-point scale appeared after each question asking the participant about their level of knowledge pertaining to the question above. We developed and revised the survey in accordance with multiple rounds of input from the members of the multidisciplinary study group, which included patient group representation. The study instrument was piloted in September 2018 with four patient groups from Egypt, Finland, Slovenia, and the UK and revised accordingly. We created and managed the final survey using REDCap.

We surveyed 30 patient groups each representing one country in the EU, Mediterranean basin, and the UK (in the EU at the time of the study). The study instrument comprised 23 questions derived from previous Hep-CORE surveys, peer-reviewed publications, verified data sources, expert group consultation, and the Global Health Sector Strategy (GHSS) [5, 16–20]. A full-length copy of the questionnaire is available in appendix 1. One community representative from each organization was responsible for completing the survey in collaboration with the organization´s board members.

The survey comprised two sets of questions: those based on WHO recommendations from the GHSS and those based on verified data sources like the European Monitoring Centre for Drugs and Drug Addiction (EMCDDA). The first set of questions (WHO recommendations) were provided to all countries and were based off the GHSS to assess implementation of WHO recommendations. The second set of questions (verified policy) were only sent to countries that had validated data sources confirm the presence of policies to assess implementation of these existing policies (Table 1). The data sources for the verified policies were selected as they either reported novel, raw data that informed the question that it was verifying or because they were reports from organizations that were responsible for collecting the monitoring data that underlie specific questions.

Table 1

Main HepCORE 2018 survey questions.

Main question (number of sub questions)	Number of countries where question is relevant (1–25)	Data source
Elimination efforts HCV (NA)	25	Polaris/GHSS
Policy barriers equity (NA)	25	GHSS
Policy stigma and discrimination (NA)	25	GHSS
Policy HCV strategy/action plan (NA)	23	GHSS/Hep-CORE 2017 [11]
Policy HCV strategy/action plan comprehensive (6)	11	GHSS
Non-hospital testing (NA)	12	HIV in Europe unpublished data
Non-hospital treatment (NA)	5	Marshall 2018a [18]
Non-specialist treatment (NA)	1	Marshall 2018a [18]
Monitoring implementation (NA)	25	GHSS
Integration of HCV services with existing care (9)	25	GHSS
Targeting of special populations for elimination (14)	25	GHSS
Fibrosis HCV treatment restrictions (NA)	12	Marshall 2018b [17] modified to add Denmark
Drug and alcohol treatment restriction (NA)	18	Marshall 2018a [18]
Needle syringe programme general population (NA)	21	EMCDDA
Opioid substitution therapy general population (NA)	21	EMCDDA
Needle syringe programme prison (NA)	3	Bielen et al. 2018 [16]
Opioid substitution therapy prison (NA)	16	EMCDDA
Testing and screening for HCV in prisons (NA)	16	Bielen et al. 2018 [16]
HCV treatment in prisons (NA)	16	Bielen et al. 2018 [16]

Questions derived from the GHSS were received by all participants, whereas the other data sources are the verified policy questions and were received only by selected countries that had the verified policy in place. Questions derived from EMCDDA data indicate that the information is derived from the country profiles of the European Monitoring Centre for Drugs and Drug Addiction.

Data analysis

We descriptively and geospatially analysed final data using R 3.6.2 and Microsoft Excel 2017 version 15.31 for storage. Frequencies and count summaries were carried out for every question for all of the possible respondents. We further estimated two sets of similarity scores that we describe below.

Policy similarity score estimation

In addition to descriptive statistics, we used the multiple correspondence analysis (MCA), a dimension reduction method to evaluate the similarity between patient group responses from different countries [21, 22]. In an MCA, the chi-squared distance is calculated between the response patterns of all the individuals. The percentage of the total variation explained is calculated for each of the new dimensions, and the new dimensions are called components [23]. The coordinates of each country (the row profiles) in the lower dimensional space are extracted and used as a similarity score between country respondents [23]. We used similarity score estimates to construct an HCV policy implementation score. The similarity score was standardized to be out of 10 points using the standard min-max normalization method [24].

We developed two similarity scores: one based on WHO recommendation questions, received by all respondents, and another based on the verified policy questions, which were only sent to countries with the relevant policy in place. For the first similarity score for WHO recommendations, only a subset of the variables were included as we wanted to only incorporate variables that would be indicative of a country’s commitment to HCV elimination as determined by multidisciplinary academic experts who were part of the study group. Fifteen experts were consulted by online questionnaire using SurveyMonkey. The survey used a 5-point Likert scale to evaluate which micro-elimination (targeted elimination that focuses on specific populations or geographies) and service integration variables the experts considered most important for inclusion into the score [25]. Questions that received a majority (greater than 50%) of positive responses were included into the score. The questionnaire is presented in appendix 2. The selected variables were then coded as 0 or 1 based on patient responses, with 0 representing a neutral, weak negative, or strong negative response, and 1 representing a slight positive or a strong positive response. We then applied the MCA to the coded data to generate the first similarity score.

The second similarity score was based on questions regarding verified policies. We used a subset of the questions about these policies, excluding questions with low numbers of respondents or low relevance, as determined during the expert consultation. The final verified questions were coded with three levels to capture the hierarchical nature of the question. The first level was coded as 0 and represented a country not receiving a question owing to not having that policy in place. The second level was coded as 1 and was assigned when a country had a verified policy in place and the patient group for that country responded with a weak negative or a strong negative response, indicating a lower level of implementation. The final level was coded as 2, which indicated that a country had a verified policy in place, and the patient respondent indicated a neutral, weak positive, or strong positive response to the implementation of said policy. In this analysis, Egypt, Israel, North Macedonia, Switzerland, and Turkey were excluded due to the lack of verified policies for opioid substitution therapy (OST) and needle syringe programmes (NSP) in the general population questions because the EMCDDA did not collect the information for these questions in these countries [20]. For the remaining countries, we then applied the MCA to the coded data to generate the second similarity score.

Proxy reference countries StagNation (no policies in place) and ElimiNation (all policies in place and implemented) were included as baseline in the first similarity score. In the second policy similarity score, ProcrastiNation (all policies, but none implemented) was also included so that the minimum and maximum of the similarity scores were representative of no implementation and maximum possible implementation respectively.

Ethics

Since the study was approved and the data were stored in Denmark, we did not need ethics approval in any other country. According to the regional representative of the Danish data protection agency and the Barcelona Institute for Global Health (ISGlobal), this study was not considered human subjects research and therefore did not require ethical review or approval. We stored all raw data on secure servers in the Capital Region of Denmark and the data were managed according to Danish regulations. All off the code and data to reproduce this analysis can be found at https://osf.io/mh79q/.

Results

Participants in 25 of 30 (83.3%) countries responded. Two of the countries that responded were from the Mediterranean Basin and 23 countries were from the EU/EEA or the UK.

The results of responses to the questions were considered for the policy similarity scores are presented in Table 2. Among WHO recommendation variables considered for inclusion, we limited the expert selection to only the micro-elimination and service integration subsets of questions (Table 2) as these questions fall along the same underlying concept. Experts indicated that for the micro-elimination variables, responses on migrants, PWID, prisoners, and sex workers were the most important for inclusion. For the service integration variables, the experts highlighted the importance of HCV service integration with blood safety, harm reduction, and migrant health services. We used the binary responses to these seven items to generate the first similarity score for the countries.

Table 2

Likert point breakdown of questions and sub-questions considered for inclusion into the policy similarity scores.

	Strong positive	Weak positive	Neutral	Weak negative	Strong negative	Not applicable
Total responses, n	243	192	166	126	89	134
WHO recommendation questions, n (%)
GHSS monitoring goal	3 (1.2)	8 (4.2)	6 (3.6)	5 (4.0)	3 (3.4)	0 (0.0)
Policy barriers equity GHSS	5 (2.1)	8 (4.2)	8 (4.8)	3 (2.4)	1 (1.1)	0 (0.0)
Policy stigma and discrimination	0 (0.0)	8 (4.2)	9 (5.4)	5 (4.0)	3 (3.4)	0 (0.0)
WHO recommendation: Micro elimination sub-questions, n (%)
Generational cohort	2 (0.8)	3 (1.6)	11 (6.6)	4 (3.2)	5 (5.6)	0 (0.0)
Haemodialysis patients	16 (6.6)	3 (1.6)	4 (2.4)	2 (1.6)	0 (0.0)	0 (0.0)
Haemophilia patients	16 (6.6)	3 (1.6)	4 (2.4)	2 (1.6)	0 (0.0)	0 (0.0)
Men who have sex with men	5 (2.1)	9 (4.7)	6 (3.6)	3 (2.4)	2 (2.2)	0 (0.0)
Migrants*	2 (0.8)	3 (1.6)	6 (3.6)	7 (5.6)	7 (7.9)	0 (0.0)
Patients with advanced liver disease	12 (4.9)	9 (4.7)	2 (1.2)	2 (1.6)	0 (0.0)	0 (0.0)
People living with HIV	17 (7.0)	6 (3.1)	1 (0.6)	1 (0.8)	0 (0.0)	0 (0.0)
People who inject drugs*	9 (3.7)	9 (4.7)	4 (2.4)	3 (2.4)	0 (0.0)	0 (0.0)
Prisoners*	6 (2.5)	3 (1.6)	7 (4.2)	7 (5.6)	2 (2.2)	0 (0.0)
Sex workers*	2 (0.8)	5 (2.6)	4 (2.4)	8 (6.3)	6 (6.7)	0 (0.0)
Thalassaemia patients	9 (3.7)	1 (0.5)	5 (3.0)	3 (2.4)	7 (7.9)	0 (0.0)
Transgender people	1 (0.4)	1 (0.5)	7 (4.2)	9 (7.1)	7 (7.9)	0 (0.0)
Transplantation patients	17 (7.0)	5 (2.6)	1 (0.6)	0 (0.0)	2 (2.2)	0 (0.0)
Veteran/military personnel	6 (2.5)	3 (1.6)	5 (3.0)	3 (2.4)	8 (9.0)	0 (0.0)
WHO recommendation: Service integration sub-questions, n (%)
Alcohol use services	2 (0.8)	5 (2.6)	5 (3.0)	7 (5.6)	6 (6.7)	0 (0.0)
Blood safety*	17 (7.0)	4 (2.1)	1 (0.6)	3 (2.4)	0 (0.0)	0 (0.0)
Cancer prevention and management	3 (1.2)	8 (4.2)	7 (4.2)	5 (4.0)	2 (2.2)	0 (0.0)
Haemodialysis centres	16 (6.6)	4 (2.1)	3 (1.8)	2 (1.6)	0 (0.0)	0 (0.0)
Harm reduction services*	5 (2.1)	10 (5.2)	5 (3.0)	3 (2.4)	2 (2.2)	0 (0.0)
HIV treatment clinic	15 (6.2)	7 (3.6)	2 (1.2)	1 (0.8)	0 (0.0)	0 (0.0)
Migrant health services*	3 (1.2)	3 (1.6)	4 (2.4)	7 (5.6)	8 (9.0)	0 (0.0)
NCD prevention and management	2 (0.8)	4 (2.1)	7 (4.2)	6 (4.8)	6 (6.7)	0 (0.0)
STI and reproductive health clinics	5 (2.1)	11 (5.7)	5 (3.0)	2 (1.6)	2 (2.2)	0 (0.0)
Verified questions, n (%)
Drug and alcohol restriction**	5 (2.1)	6 (3.1)	4 (2.4)	2 (1.6)	1 (1.1)	7 (5.2)
Non-hospital testing	3 (1.2)	3 (1.6)	3 (1.8)	2 (1.6)	1 (1.1)	13 (9.7)
Non-hospital treatment	0 (0.0)	5 (2.6)	0 (0.0)	0 (0.0)	0 (0.0)	20 (14.9)
Non-specialist treatment	0 (0.0)	0 (0.0)	1 (0.6)	0 (0.0)	0 (0.0)	24 (17.9)
NSP general population**	5 (2.1)	5 (2.6)	6 (3.6)	4 (3.2)	1 (1.1)	4 (3.0)
NSP prison**	0 (0.0)	0 (0.0)	2 (1.2)	1 (0.8)	0 (0.0)	22 (16.4)
OST general population**	8 (3.3)	6 (3.1)	5 (3.0)	2 (1.6)	0 (0.0)	4 (3.0)
OST prison**	4 (1.6)	5 (2.6)	4 (2.4)	2 (1.6)	1 (1.1)	9 (6.7)
Testing and screening of HCV in prisons**	2 (0.8)	5 (2.6)	4 (2.4)	3 (2.4)	2 (2.2)	9 (6.7)
Treatment of HCV in prisons**	3 (1.2)	6 (3.1)	3 (1.8)	3 (2.4)	1 (1.1)	9 (6.7)
Fibrosis treatment restrictions for HCV**	7 (2.9)	3 (1.6)	1 (0.6)	1 (0.8)	0 (0.0)	13 (9.7)

Variables denoted with * were included into the first similarity score based off WHO recommendations and variables that are marked with ** were included into the second similarity score based off verified policies. GHSS = Global Health Sector Strategy, NCD = non-communicable disease, STI = sexually transmitted infection, NSP = needle-syringe programme, OST = opioid substitution therapy, HCV = hepatitis C virus

In the MCA for WHO recommendations, the first component accounted for 75.5% of the total inertia in the subset data, whereas the second component accounted for 2.9% of inertia (S1 Fig). For the first component, all of the negative outcomes of the dichotomous variables were associated with negative scores, while all of the positive outcomes of the dichotomous variables were associated with positive scores (S1 Fig). The variables with the greatest weight in determining a positive score were a positive response towards HCV micro-elimination among migrants, prisoners and sex workers and the integration of HCV testing and treatment with migrant health services. Conversely, the responses that were associated with the most negative scores were not having HCV micro-elimination efforts among PWID, not having HCV integration with harm reduction services, and a lack of HCV blood safety testing (S1 Fig).

The extracted row profiles for the countries from WHO recommendation MCA are presented in Fig 1. The countries with the highest scores were Cyprus, Netherlands, Portugal, Slovenia, and Sweden (all having similarity scores of 10). These countries responded positively to all of the binary indicators in WHO recommendation similarity score. The lowest scoring country was Bulgaria (score of 0), which responded negatively to all but two of the binary indicators. All of the other scores ranged between 0 and 10, forming a distribution of countries along the spectrum of policy elimination (Fig 1).

Fig 1

WHO recommendation similarity scores for the studied countries.

Summary of the standardized scores for the different countries according to row profiles of the first components of the MCA.

For the verified policies similarity score, we considered for inclusion all the questions under the subheading “verified questions” in Table 2. We included the following variables: fibrosis HCV treatment restrictions; NSP in the general population; OST in the general population; NSP in prisons; OST in prisons; testing/screening for HCV in prisons; and the treatment of HCV in prisons. The MCA of these variables yielded a two-dimensional solution in which the first component accounted for 44.3% of the inertia in the data, and the second component accounted for 34.6% of the inertia in the dataset (S2 Fig). The responses that mapped the closest to the first component were whether a country had a verified policy in place or not, with positive values indicating the presence of verified policies and negative values indicating the absence of verified policies. The second dimension was interpreted as whether a policy was being implemented in practice. Negative values represent policies that are in place but not well implemented, and positive values represent policies that are in place and well implemented (S2 Fig). The coordinates for both of the dimensions of the second policy similarity score were extracted and are presented in Fig 2.

Fig 2

Verified policy similarity scores for the different countries (n = 20).

The similarity score of the countries based on their responses to the verified questions and whether a particular policy was in place.

Spain had the highest first component score (10) of the verified policies similarity score (i.e. the presence or absence of verified policies), followed by Portugal (9.48), Sweden (9.48), Austria (9.48), and the United Kingdom (9.48). Bosnia and Herzegovina, which only had an OST and NSP programme for non-incarcerated individuals, had the lowest score 3.87 (Fig 2). Cyprus had the next lowest score, which also only had an OST and NSP programme, like Ukraine, but were reported as being well implemented.

Spain had the highest score of the second component as well (the proportion of verified policies that are well implemented, according to the patient group respondent) with a maximum score of 10 (Fig 2). The lowest score was Finland, which had a score of 5.54. The patient respondent reported that of all the policies in place, NSP in the general population, OST in the general population, and HCV testing/screening in prisons were being adequately implemented. However, drug–alcohol restrictions, the lifting of fibrosis severity HCV treatment restrictions, and HCV treatment in prisons were not well implemented.

Table 3 presents the reported similarity score for WHO recommendations, the two similarity scores for the verified policies, the difference between the WHO recommendation similarity score and the first verified policy similarity score for each applicable country, and the mean confidence score of the respondent for each country. Positive values of the difference between WHO recommendation similarity score and the first similarity score for the verified policies may reflect poor engagement with patients in the discussion of the current status of HCV elimination in their country. Negative values of this difference could suggest poor implementation of policies. The country with the largest negative gap between the verified policy similarity score and WHO recommendation score was Bulgaria, with a difference of –7.86. The largest positive gap was Cyprus, with a difference of 5.59 between WHO recommendation score and the first dimension of the verified policy similarity score. The mean confidence score for Bulgaria was 2.53, and for Cyprus the mean confidence score was 3.38 (Table 3).

Table 3

The WHO recommendation similarity score of the two similarity scores from the verified policies, the difference between WHO recommendation score and first similarity score of verified policies, and the mean confidence score for all of the countries.

Country	WHO recommendation similarity score	Similarity score verified policies dimension 1	Difference of WHO score and verified policy dim 1	Similarity score verified policies dimension 2	Overall confidence mean (SD)
Bulgaria	0	7.86	-7.86	7.5	2.53 (0.77)
Spain	6.29	10	-3.71	10	2.65 (0.61)
Poland	4.32	7.59	-3.27	5.55	3.24 (0.75)
Finland	5.89	8.71	-2.82	5.54	3.11 (0.46)
Romania	5.4	7.21	-1.81	8.39	3.29 (0.69)
United Kingdom	7.77	9.48	-1.71	9.71	3.70 (0.66)
Austria	7.77	9.48	-1.71	9.71	3.06 (0.64)
Croatia	6.29	7.25	-0.96	8.71	3.56 (0.51)
Norway	5.33	6.25	-0.92	8.91	3.21 (0.89)
Denmark	8.79	8.91	-0.12	5.76	1.95 (0.52)
Belgium	8.98	8.63	0.35	9.7	2.12 (0.81)
Sweden	10	9.48	0.52	9.71	3.11 (0.83)
Portugal	10	9.48	0.52	8.74	3.89 (0.32)
Ukraine	6.57	5.83	0.74	6.74	2.71 (0.47)
Bosnia and Herzegovina	4.71	3.87	0.84	7.99	2.69 (0.48)
Serbia	6.2	4.84	1.36	8.29	3.56 (0.63)
Slovenia	10	8.63	1.37	9.7	3.76 (0.44)
Netherlands	10	8.62	1.38	9.32	2.67 (0.97)
Slovakia	8.51	6.78	1.73	9.06	3.19 (0.40)
Cyprus	10	4.41	5.59	8.65	3.38 (0.51)
Switzerland	4.71	NA	NA	NA	3.77 (0.44)
Egypt	6.29	NA	NA	NA	3.90 (0.32)
Turkey	2.22	NA	NA	NA	3.83 (0.39)
North Macedonia	4.71	NA	NA	NA	3.42 (0.52)
Israel	4.71	NA	NA	NA	4.00 (0)
ProcrastiNation	NA	9.22	NA	0	NA
ElimiNation	10	10	-	10	NA
StagNation	0	0	-	8.52	NA

Discussion

The Hep-CORE 2018 study focused on how well countries were implementing WHO recommendations from the GHSS as well as verified policies to eliminate viral hepatitis. We analyzed the similarity of different country responses for a subset of WHO recommendations and a subset of verified policy questions. Patient group respondents in 25 countries indicated incomplete implementation of WHO recommended HCV policy implementation across Europe, with concerning intercountry discrepancies evidenced.

Currently, only 12 countries are reported to be on track to meet WHO elimination targets for HCV—eight of these are in WHO European Region and seven were among our study countries [19]. Countries that are on track and included in this study are Egypt, the Netherlands, Spain, Switzerland, and the UK. France and Italy are both on track and patients’ groups were sent surveys but did not respond. For Egypt and Switzerland, we did not calculate a difference because both countries were excluded from the verified similarity analysis and therefore did not have a score. The difference for both the UK and Spain were negative, suggesting the under-implementation of policies from the perspective of the respondents. In contrast, the Netherlands had a positive difference, suggesting that policy-makers and the medical community could better engage patient advocacy groups to highlight policies that are in place.

Although Egypt and Switzerland did not have a score generated from the verified similarity score, both had low scores (6.29 and 4.71, respectively) relative to the possible maximum of 10 for WHO recommendation similarity score. These low scores indicate that vulnerable groups, such as migrants, are not targeted well. This finding highlights an issue with WHO 2030 goals and what is considered the “elimination” of HCV as a public health threat. For example, there is a good probability that both Switzerland and Egypt will meet the WHO 2030 HCV elimination targets at a population level despite not targeting all vulnerable groups. As a consequence, some vulnerable groups may be left behind. Therefore, it is important to assess if and how the most vulnerable and/or marginalized patients are included in policy and implementation of governmental HCV elimination strategies, even if a country might be on track for HCV elimination. This idea is further reinforced by the findings of the recent Lancet Commission on the acceleration of viral hepatitis elimination [14]. In the Commission, a policy score card was created for select countries, including five (Egypt, Poland, Romania, Spain, and the UK) that overlap with our study. The scores we generated indicated that Egypt could be leaving marginalized populations, like PWID, behind. Likewise, the Lancet Commission, found that Egypt does not have a harm reduction policy in place. The Lancet Commission also identified policy gaps in Poland and Romania, such as the lack of a publicly-funded screening programme and reliable national epidemiological data, which supports the low scores we recorded for the countries in this study. Conversely, the Commission reported that Spain and the UK have both of these policies in place, and we found that these countries scored highly, outranking Egypt, Poland, and Romania [14].

Limitations

The Hep-CORE 2018 study relies on only one stakeholder group for information; therefore, inferential statistics cannot be conducted at the country level as we only have a single replicate. Additionally, this means that a random sample was not possible as we could not randomly select from any groups. Although, a random sample for this kind of research is not desirable since we surveyed key stakeholders whose perspectives were most relevant to the research questions rather than those of random patient groups. We understand that our sampling method could introduce a bias since respondents likely had similar education and sociodemographic characteristics. However, this selection is desirable in our study as we tried to obtain an accurate view of HCV policy implementation from patient groups rather than determine patients’ knowledge about HCV policy. Furthermore, the survey could not be altered once it was launched, potentially leading to outcome censoring if a policy changed while the survey was being completed. For example, this survey was conducted in Q4 2018, but Egypt started a national screening programme that would include all subgroups in the study in Q2 2019, which would not be captured by this study. Furthermore, Egypt’s new approach is representative of where a macro-elimination approach is possible due to government commitment, and micro-elimination in this scenario is not necessarily needed [26]. Another limitation of the cross-sectional nature of this study is that a policy might not have been in place long enough for a patient group to accurately evaluate its implementation. In the future, it would be ideal if the data needed to build the score could be collected every 6 months and serve as a progress monitoring tool; however, a lack of funding constrains the ability to create such projects and efforts. Additionally, involving drug user groups and other organisations whose members might not be well represented by patient groups would strengthen reporting. Additionally, the survey was only disseminated in English, which may have limited the accuracy of the responses as most respondents were non-native English speakers.

For future studies, it will be important to explore new approaches to hepatitis policy monitoring, such as cross-referencing data collected from civil society with the data from other sources including publicly available DAA reimbursement records, government health officials, and clinicians. The generalizability of the MCA method used to evaluate the responding countries is another important limitation. MCA methods used to make the similarity scores tend to produce unstable results because they depend on the sample used. The inclusion of anomalous data, choices carried out by the researchers when reducing the categories of the variables, and other factors could have affected the final results and country rankings [27]. However, the use of standardized countries helped stabilize those estimates and provide meaning to the numerical values of the similarity score, a technique we have validated elsewhere [28]. Although, that study does not levy patient or civil society information like this present study. Finally, noting that the scores are derived from patient responses, these policy similarity scores should not be used in isolation but as an aid in decisionmaking [29].

Conclusions

Patient groups from all 25 studied countries identified areas of improvement in HCV policy development and implementation with substantial inter-country variation. Policy improvements are essential for the entire European Region to achieve the WHO 2030 viral hepatitis elimination goal. Civil society and the government must take more action to monitor implementation of current policies. Crucially, European countries must ensure acceptable and accessible HCV service provision for high-risk populations, who continue to be overlooked in many settings.

MCA outputs for WHO recommendation index.

The MCA determined weight for all of the categories for the WHO recommendation index.

(TIF)

Click here for additional data file.

MAC outputs for the verified index.

The MCA determined weights for all of the categories for the verified index.

(TIF)

Click here for additional data file.

Hep-CORE survey.

This is the complete survey that was used along with code fields.

(PDF)

Click here for additional data file.

Weighting expert survey.

This is the complete survey that was used to ask experts what should be included into the index.

(PDF)

Click here for additional data file.

1 Jun 2020

PONE-D-20-09886

The Hep-CORE Policy Score: A European hepatitis C national policy implementation ranking

PLOS ONE

Dear Dr. Lazarus,

Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process.

I enjoyed the study results however there are concerns from reviewers should be considered carefully before acceptance of manuscript for publication in PLOS ONE.

Please submit your revised manuscript by Jul 16 2020 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org. When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file.

Please include the following items when submitting your revised manuscript:

A rebuttal letter that responds to each point raised by the academic editor and reviewer(s). You should upload this letter as a separate file labeled 'Response to Reviewers'.

A marked-up copy of your manuscript that highlights changes made to the original version. You should upload this as a separate file labeled 'Revised Manuscript with Track Changes'.

An unmarked version of your revised paper without tracked changes. You should upload this as a separate file labeled 'Manuscript'.

If you would like to make changes to your financial disclosure, please include your updated statement in your cover letter. Guidelines for resubmitting your figure files are available below the reviewer comments at the end of this letter.

If applicable, we recommend that you deposit your laboratory protocols in protocols.io to enhance the reproducibility of your results. Protocols.io assigns your protocol its own identifier (DOI) so that it can be cited independently in the future. For instructions see: http://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols

We look forward to receiving your revised manuscript.

Kind regards,

Heidar Sharafi

Academic Editor

PLOS ONE

Additional Editor Comments:

1. I tried to access the data of the study however it needed the approval from authors and also after being approved nothing was found in the folders. Authors should follow the data policy of PLOS.

2. I could not find the supplementary Figures 1 and 2 in the submission.

Journal requirements:

When submitting your revision, we need you to address these additional requirements.

1. Please ensure that your manuscript meets PLOS ONE's style requirements, including those for file naming. The PLOS ONE style templates can be found at

https://journals.plos.org/plosone/s/file?id=wjVg/PLOSOne_formatting_sample_main_body.pdf and

https://journals.plos.org/plosone/s/file?id=ba62/PLOSOne_formatting_sample_title_authors_affiliations.pdf

2. Thank you for stating the following in the Financial Disclosure section:

'The European Liver Patients’ Association received funding from AbbVie, Gilead Sciences and MSD to carry out this study. The funders did not have any control over the study or the resulting manuscript. ICMJE forms have been provided by all authors.'

We note that you received funding from a commercial source: AbbVie, Gilead Sciences and Merck & Co.

a. Please provide an amended Competing Interests Statement that explicitly states this commercial funder, along with any other relevant declarations relating to employment, consultancy, patents, products in development, marketed products, etc.

Within this Competing Interests Statement, please confirm that this does not alter your adherence to all PLOS ONE policies on sharing data and materials by including the following statement: "This does not alter our adherence to PLOS ONE policies on sharing data and materials.” (as detailed online in our guide for authors http://journals.plos.org/plosone/s/competing-interests).  If there are restrictions on sharing of data and/or materials, please state these. Please note that we cannot proceed with consideration of your article until this information has been declared.

Pb. lease include your amended Competing Interests Statement within your cover letter. We will change the online submission form on your behalf.

Please know it is PLOS ONE policy for corresponding authors to declare, on behalf of all authors, all potential competing interests for the purposes of transparency. PLOS defines a competing interest as anything that interferes with, or could reasonably be perceived as interfering with, the full and objective presentation, peer review, editorial decision-making, or publication of research or non-research articles submitted to one of the journals. Competing interests can be financial or non-financial, professional, or personal. Competing interests can arise in relationship to an organization or another person. Please follow this link to our website for more details on competing interests: http://journals.plos.org/plosone/s/competing-interests

3. Thank you for stating the following in the Acknowledgments Section of your manuscript:

'GC is supported in part by the BRC of Imperial College NHS Trust and an NIHR Professorship. JVL is supported by a Spanish Ministry of Science, Innovation and Universities Miguel Servet grant (Instituto de Salud Carlos III/ESF, European Union (CP18/00074)). JVL further acknowledges support from the Spanish Ministry of Science, Innovation and Universities through the “Centro de Excelencia Severo Ochoa 2019-2023” Program (CEX2018-000806-S), and support from the Government of Catalonia through the CERCA Program.'

We note that you have provided funding information that is not currently declared in your Funding Statement. However, funding information should not appear in the Acknowledgments section or other areas of your manuscript. We will only publish funding information present in the Funding Statement section of the online submission form.

Please remove any funding-related text from the manuscript and let us know how you would like to update your Funding Statement. Currently, your Funding Statement reads as follows:

'The European Liver Patients’ Association received funding from AbbVie, Gilead Sciences and MSD to carry out this study. The funders did not have any control over the study or the resulting manuscript. ICMJE forms have been provided by all authors.'

4. One of the noted authors is a group; the Hep-CORE Study Group.

In addition to naming the author group, please list the individual authors and affiliations within this group in the acknowledgments section of your manuscript.

Please also indicate clearly a lead author for this group along with a contact email address.

5. Please upload a copy of Figure 5, to which you refer in your text on page 14. If the figure is no longer to be included as part of the submission please remove all reference to it within the text.

6. Please include captions for your Supporting Information files at the end of your manuscript, and update any in-text citations to match accordingly. Please see our Supporting Information guidelines for more information: http://journals.plos.org/plosone/s/supporting-information

[Note: HTML markup is below. Please do not edit.]

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: Partly

**********

2. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: I Don't Know

Reviewer #2: Yes

Reviewer #3: I Don't Know

**********

3. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: Yes

**********

4. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #1: No

Reviewer #2: Yes

Reviewer #3: Yes

**********

5. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: Dear associate editor of PLOS ONE

Many thanks for your kind invitation to review the manuscript entitled “The Hep-CORE Policy Score: A European Hepatitis C national policy implementation ranking”

In this project, 25 liver patient organizations representing 25 countries in Europe have been evaluated regarding policies for HCV elimination. Two sets of surveys have been performed (based on WHO policies and based on sources verifying existing policy). Then they determined scores for each county and finally they concluded that European region is not following WHO policies for HCV elimination goals. My comments:

1. Introduction section is well written. However, I think that authors should add a section to it regarding the aims of their project.

2. I think that the method of the abstract section is a little complicated and should be presented more simple than this so that all readers can fully understand it.

3. Regarding the methods of this project, I suggest to use an expert to review. I think it is too complicated to for a usual reader to understand it.

4. Items of questioners have been explained in detail. Sampling methods have been well discussed. I also think that this study has not ethical problems.

5. I suggest that authors summarize the results section. In this section readers encounter with huge data and it leads to confusion. I think some of them should be transferred in the supplementary section. I recommend that authors use some figures for better representing their data.

Overall comment:

The results of this study seems to be very important and it seriously needs attention. However, I think that the manuscript should be summarized and written a in better style for better understanding.

Best

reviewer

Reviewer #2: Dear Editor

Thanks for inviting me to review the manuscript PONE-D-20-09886 entitled "The Hep-CORE Policy Score: A European hepatitis C national policy implementation ranking". I have only two minor comments to the authors:

- The scoring method for each item may be unclear for the readers. It could be better if you mention which score belongs to which answer. Also, please mention if all items had similar scores for Strong positive, Weak positive, Neutral, Weak negative,

and Strong negative answers. If not, please specify which one has a different scoring.

- Please consider two decimals for each number showing a central tendency or SD in table 3 (e.g. 5.40 instead of 5.4).

Regards

Reviewer

Reviewer #3: This study assess the extent of policy implementation from the perspective of liver patient groups. However the implications of patients groups seems minimal, only answering the survey. None of these organizations are among the authors.

The study have some important limitations. Firstly would be important to have more details on the patients organizations included in the study. They represented the country or are more local associations? To translate the answers of a patient’s organization to all country could not be representative of the country. Secondly, the survey was performed in 2018 and the field is moving quickly, the authors should comment on that

Two of the countries that responded were from the Mediterranean Basin and 23 countries were from the EU/EEA or the UK. Are these two countries outside EU/EEA?

134 surveys had missed responses? The impact on the missing response and the countries with missed responses should be discuss and give more details (table2)

Please comment that two big European countries such as Italy and Germany are not included

The title of the manuscript is not accurate. The authors have to add patients organizations in the title because the manuscript reflects the point of view of these organizations

**********

6. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files.

If you choose “no”, your identity will remain anonymous but your review may still be made public.

Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy.

Reviewer #1: No

Reviewer #2: Yes: Hamidreza Karimi-Sari, MD

Reviewer #3: No

[NOTE: If reviewer comments were submitted as an attachment file, they will be attached to this email and accessible via the submission site. Please log into your account, locate the manuscript record, and check for the action link "View Attachments". If this link does not appear, there are no attachment files.]

While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool, https://pacev2.apexcovantage.com/. PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Registration is free. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email PLOS at figures@plos.org. Please note that Supporting Information files do not need this step.

19 Jun 2020

Additional Editor Comments:

1. I tried to access the data of the study however it needed the approval from authors and also after being approved nothing was found in the folders. Authors should follow the data policy of PLOS.

Response: Full access has been given for the folders and the data files and coding scripts should be fully accessible. Please contact me if you cannot access the files.

2. I could not find the supplementary Figures 1 and 2 in the submission.

Response: Supplementary figures have been provided as well as supplementary files with the naming format of PLOS ONE

Journal requirements: When submitting your revision, we need you to address these additional requirements.

1. Please ensure that your manuscript meets PLOS ONE's style requirements, including those for file naming. The PLOS ONE style templates can be found at

https://journals.plos.org/plosone/s/file?id=wjVg/PLOSOne_formatting_sample_main_body.pdf and

https://journals.plos.org/plosone/s/file?id=ba62/PLOSOne_formatting_sample_title_authors_affiliations.pdf

Response: We have formatted our manuscript and file names according to the guidelines in the link above.

2. Thank you for stating the following in the Financial Disclosure section:

'The European Liver Patients’ Association received funding from AbbVie, Gilead Sciences and MSD to carry out this study. The funders did not have any control over the study or the resulting manuscript. ICMJE forms have been provided by all authors.'We note that you received funding from a commercial source: AbbVie, Gilead Sciences and Merck & Co.

a. Please provide an amended Competing Interests Statement that explicitly states this commercial funder, along with any other relevant declarations relating to employment, consultancy, patents, products in development, marketed products, etc.

Within this Competing Interests Statement, please confirm that this does not alter your adherence to all PLOS ONE policies on sharing data and materials by including the following statement: "This does not alter our adherence to PLOS ONE policies on sharing data and materials.” (as detailed online in our guide for authors http://journals.plos.org/plosone/s/competing-interests).  If there are restrictions on sharing of data and/or materials, please state these. Please note that we cannot proceed with consideration of your article until this information has been declared.

Please include your amended Competing Interests Statement within your cover letter. We will change the online submission form on your behalf.

Please know it is PLOS ONE policy for corresponding authors to declare, on behalf of all authors, all potential competing interests for the purposes of transparency. PLOS defines a competing interest as anything that interferes with, or could reasonably be perceived as interfering with, the full and objective presentation, peer review, editorial decision-making, or publication of research or non-research articles submitted to one of the journals. Competing interests can be financial or non-financial, professional, or personal. Competing interests can arise in relationship to an organization or another person. Please follow this link to our website for more details on competing interests: http://journals.plos.org/plosone/s/competing-interests

Response: We have amended our competing interest statement in our cover letter as requested. Please let us know if you require more information.

3. Thank you for stating the following in the Acknowledgments Section of your manuscript:

'GC is supported in part by the BRC of Imperial College NHS Trust and an NIHR Professorship. JVL is supported by a Spanish Ministry of Science, Innovation and Universities Miguel Servet grant (Instituto de Salud Carlos III/ESF, European Union (CP18/00074)). JVL further acknowledges support from the Spanish Ministry of Science, Innovation and Universities through the “Centro de Excelencia Severo Ochoa 2019-2023” Program (CEX2018-000806-S), and support from the Government of Catalonia through the CERCA Program.'

We note that you have provided funding information that is not currently declared in your Funding Statement. However, funding information should not appear in the Acknowledgments section or other areas of your manuscript. We will only publish funding information present in the Funding Statement section of the online submission form.

Please remove any funding-related text from the manuscript and let us know how you would like to update your Funding Statement. Currently, your Funding Statement reads as follows:

'The European Liver Patients’ Association received funding from AbbVie, Gilead Sciences and MSD to carry out this study. The funders did not have any control over the study or the resulting manuscript. ICMJE forms have been provided by all authors.'

Response: We have fixed our acknowledgement and funding section and have added the amended funding section to the cover letter. Please let us know if you require further information.

4. One of the noted authors is a group; the Hep-CORE Study Group.

In addition to naming the author group, please list the individual authors and affiliations within this group in the acknowledgments section of your manuscript.

Response: We have added to acknowledgements that the lead of the Hep-CORE study group is JVL who is also the corresponding author for the paper and includes GSC, SJH, MJR, MM, MH, AMM, and HR among the authors and Charles Gore, Greet Hendrickx, Achim Kautz, Luis Mendao, Antons Mozalevskis, Tatjana Reic, and Eberhard Schatz who were not among the authors.

.Please also indicate clearly a lead author for this group along with a contact email address.

Response: We have not added the email but indicate that the lead of the study group is also the corresponding author in the acknowledgments of the paper and thus can be contacted.

5. Please upload a copy of Figure 5, to which you refer in your text on page 14. If the figure is no longer to be included as part of the submission please remove all reference to it within the text.

Response: Figure 5 was a typo and it meant to read figure 2. We have corrected this.

6. Please include captions for your Supporting Information files at the end of your manuscript, and update any in-text citations to match accordingly. Please see our Supporting Information guidelines for more information: http://journals.plos.org/plosone/s/supporting-information

Response: We have made a Supporting information section with the names and captions

Reviewers' comments:

Reviewer's Responses to Questions

Reviewer #1: Dear associate editor of PLOS ONE
Many thanks for your kind invitation to review the manuscript entitled “The Hep-CORE Policy Score: A European Hepatitis C national policy implementation ranking”
In this project, 25 liver patient organizations representing 25 countries in Europe have been evaluated regarding policies for HCV elimination. Two sets of surveys have been performed (based on WHO policies and based on sources verifying existing policy). Then they determined scores for each county and finally they concluded that European region is not following WHO policies for HCV elimination goals

My comments:
1. Introduction section is well written. However, I think that authors should add a section to it regarding the aims of their project.

Response: We believe that this requirement is satisfied on page 4 on lines 109 to 111 with the text, “Inspired by this call, Hep-CORE 2018 set out to assess whether known national HCV policies in Europe, the United Kingdom (UK), and the Mediterranean Basin are functioning in practice and to score the extent of implementation according to patient advocacy groups”

2. I think that the method of the abstract section is a little complicated and should be presented more simple than this so that all readers can fully understand it.

Response: We have tried to simplify the methods in the abstract to make them simpler and straight forward and avoid a lot of potentially misleading jargon.

3. Regarding the methods of this project, I suggest to use an expert to review. I think it is too complicated to for a usual reader to understand it.

Response: We agree that the methods in this paper can be a little daunting, but for what it is worth we consulted one of the world expert on the methodology who wrote the text book on the subject, Dr Michael Greenacre. Based on his input, we developed methods.

4. Items of questioners have been explained in detail. Sampling methods have been well discussed. I also think that this study has not ethical problems.

Response: Thank you.

5. I suggest that authors summarize the results section. In this section readers encounter with huge data and it leads to confusion. I think some of them should be transferred in the supplementary section. I recommend that authors use some figures for better representing their data.

Response: We have tried to simplify the result; however, there is a lot of information in this study to present and some of this is unavoidable. We believe that we have presented this large volume of information in a logical fashion.

Overall comment:
The results of this study seems to be very important and it seriously needs attention. However, I think that the manuscript should be summarized and written a in better style for better understanding.
Best
reviewer

Reviewer #2: Dear Editor
Thanks for inviting me to review the manuscript PONE-D-20-09886 entitled "The Hep-CORE Policy Score: A European hepatitis C national policy implementation ranking". I have only two minor comments to the authors:

- The scoring method for each item may be unclear for the readers. It could be better if you mention which score belongs to which answer. Also, please mention if all items had similar scores for Strong positive, Weak positive, Neutral, Weak negative,
and Strong negative answers. If not, please specify which one has a different scoring.

Response: This information is provided in the supplementary figures that shows the value of how much each level of response was worth. The reviewer; however, must be mistaken on the value we assigned as we did not assign values to each of the 5 levels but rather we grouped the variables and analyzed them as three distinct levels of negative, neutral, and positive, which have weights in the scores for each item. These weights were the ones used in the score and are part of the supplemental figures.

- Please consider two decimals for each number showing a central tendency or SD in table 3 (e.g. 5.40 instead of 5.4).

Response: This would not be appropriate as for simple count data with values less than 10 and the n being in the double digits the correct number of decimals would be one. We maintain that we should only present to one decimal and that the data provided do not allow us to present two decimals even though we could output it this would not be scientifically accurate due to the rules of significant digits.

Regards
Reviewer

Reviewer #3: This study assess the extent of policy implementation from the perspective of liver patient groups. However the implications of patients groups seems minimal, only answering the survey. None of these organizations are among the authors.

Response: We disagree as both Dr Magdalena Harris and Dr Ammal M Metwally are both patients with lived experience as well as academics and are authors of the paper.

The study have some important limitations. Firstly would be important to have more details on the patients organizations included in the study. They represented the country or are more local associations? To translate the answers of a patient’s organization to all country could not be representative of the country. Secondly, the survey was performed in 2018 and the field is moving quickly, the authors should comment on that

Response: We have provided information on the patient organizations already in the paper and do not feel like we can expand in part because there are aspects that we cannot include about the patient organization due to confidentiality reasons such as who answered the survey. The fact that the survey was only in English is now mentioned in the limitation on Page 18 lines 398 to 400. We have also already discussed the cross-sectional nature of the study in the limitations and re the need to comment on the survey being done in 2018, please page 18 lines 387 to 391 as well as lines 393 to 397

Two of the countries that responded were from the Mediterranean Basin and 23 countries were from the EU/EEA or the UK. Are these two countries outside EU/EEA?

Response: Yes they are outside the EU/EEA and neither are the UK.

134 surveys had missed responses? The impact on the missing response and the countries with missed responses should be discuss and give more details (table2)

Response: I understand why the reviewer may be confused, but we had complete data for all the responses so we did not have missing data besides the non-responses which were for 3 entire countries and is a refusal to participate not missing data per say. To address the concern of the reviewers we have removed the “/missing” from the header in Table 2 so that it only reads non-applicable which is the correct designation of everything in that column.

Please comment that two big European countries such as Italy and Germany are not included
The title of the manuscript is not accurate. The authors have to add patients organizations in the title because the manuscript reflects the point of view of these organizations

Response: We have added patient organizations in the title to make it more informative, “The Hep-CORE Policy Score: A European hepatitis C national policy implementation ranking with data from patient organizations”. We cannot elaborate further on why Italy and Germany were not included as the patient organizations from those countries declined to participate.

While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool, https://pacev2.apexcovantage.com/. PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Registration is free. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email PLOS at figures@plos.org. Please note that Supporting Information files do not need this step.

Response: All of our figures have been put through PACE and are to the standards of PlosONE

Submitted filename: Response to reviewers.docx

Click here for additional data file.

22 Jun 2020

The Hep-CORE Policy Score: A European hepatitis C national policy implementation ranking based on patient organization data

PONE-D-20-09886R1

Dear Dr. Lazarus,

We’re pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it meets all outstanding technical requirements.

Within one week, you’ll receive an e-mail detailing the required amendments. When these have been addressed, you’ll receive a formal acceptance letter and your manuscript will be scheduled for publication.

An invoice for payment will follow shortly after the formal acceptance. To ensure an efficient process, please log into Editorial Manager at http://www.editorialmanager.com/pone/, click the 'Update My Information' link at the top of the page, and double check that your user information is up-to-date. If you have any billing related questions, please contact our Author Billing department directly at authorbilling@plos.org.

If your institution or institutions have a press office, please notify them about your upcoming paper to help maximize its impact. If they’ll be preparing press materials, please inform our press team as soon as possible -- no later than 48 hours after receiving the formal acceptance. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information, please contact onepress@plos.org.

Kind regards,

Heidar Sharafi

Academic Editor

PLOS ONE

8 Jul 2020

PONE-D-20-09886R1

The Hep-CORE Policy Score: A European hepatitis C national policy implementation ranking based on patient organization data

Dear Dr. Lazarus:

I'm pleased to inform you that your manuscript has been deemed suitable for publication in PLOS ONE. Congratulations! Your manuscript is now with our production department.

If your institution or institutions have a press office, please let them know about your upcoming paper now to help maximize its impact. If they'll be preparing press materials, please inform our press team within the next 48 hours. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information please contact onepress@plos.org.

If we can help with anything else, please email us at plosone@plos.org.

Thank you for submitting your work to PLOS ONE and supporting open access.

Kind regards,

PLOS ONE Editorial Office Staff

on behalf of

Dr. Heidar Sharafi

Academic Editor

PLOS ONE