Guidance
Appendix C The evidence
This appendix lists the evidence statements from two reviews, provided by external contractors (see appendix A and appendix E) and links them to the relevant recommendations. See appendix B for the meaning of the (++), (+) and (-) quality assessments referred to in the evidence statements.
The two reviews are:
-
Review 1: 'A systematic review of qualitative research on the views, perspectives and experiences of hepatitis B and C testing among practitioners and people at greatest risk of infection'.
-
Review 2: 'A systematic review of the effectiveness and cost effectiveness of interventions aimed at raising awareness and engaging with groups who are at increased risk of hepatitis B and C infection'.
The evidence statements are short summaries of evidence, in a review, report or paper (provided by an expert in the topic area). Each statement has a short code indicating which document the evidence has come from. The letter(s) in the code refer to the type of document the statement is from, and the numbers refer to the document number, and the number of the evidence statement in the document.
Evidence statement Q1 indicates that the linked statement is numbered 1 in review 1. Evidence statement E3 indicates that the linked statement is numbered 3 in review 2.
See the full reviews and economic analysis. Where a recommendation is not directly taken from the evidence statements, but is inferred from the evidence, this is indicated by IDE (inference derived from the evidence).
Where the Programme Development Group (PDG) has considered other evidence, it is linked to the appropriate recommendation below. It is also listed in the additional evidence section of this appendix.
Recommendation 1: evidence statements: Q1, Q2, Q3, Q4, Q5, Q8, Q9, Q10, E1; IDE
Recommendation 2: evidence statements: Q1, Q2, Q3, Q4, Q5, Q8, Q9, Q10, Q14, Q15, Q16, Q23, Q28, Q29, E1; IDE
Recommendation 3: evidence statements: Q2, Q18, Q20, Q21, Q28, Q29, Q30, E2, E5, E8; IDE
Recommendation 4: evidence statements: Q28, E5, E6, E11
Recommendation 5: evidence statements: Q16, Q27, Q28, E1, E6; IDE
Recommendation 6: evidence statements: Q18, Q20, Q21, Q24, Q25, Q28, Q29, Q30, E1, E4, E5, E6, E7, E8, E9; IDE
Recommendation 7: IDE
Recommendation 8: IDE
Recommendation 9: IDE
Recommendation 10: Q7, E5; IDE
Recommendation 11: evidence statements: IDE
Evidence statements
Please note that the wording of some evidence statements has been altered slightly from those in the evidence review(s) to make them more consistent with each other and NICE's standard house style. The superscript numbers refer to the studies cited beneath each statement. The full references for those studies can be found in the reviews.
Evidence statement Q1
Understanding and awareness of hepatitis B among people born in countries with intermediate and high endemicity may be strongly influenced by their personal experiences and cultural beliefs (two [++], one [+]).
Evidence statement Q2
People born in countries with intermediate and high endemicity for hepatitis B may confuse the various forms of hepatitis and the relationship between hepatitis and HIV, and they may commonly hold inaccurate beliefs about transmission risks (two [++], one [+]). The lack of, or gaps in, knowledge about hepatitis B identified among some healthcare professionals (two [++]) may contribute to or compound inadequate knowledge about hepatitis B among groups at a high risk of infection.
Evidence statement Q3
People born in countries with intermediate and high endemicity for hepatitis B may commonly cite access to or contamination of food, or cultural practices associated with sharing food and communal eating, as the main cause of hepatitis B transmission (three [++] and one [+]). Although vertical transmission of hepatitis B was acknowledged in some studies, sexual transmission of hepatitis B was infrequently mentioned; overall, the evidence suggests that groups at a high risk of infection do not perceive hepatitis B as a sexually transmitted infection (three [++]).
Evidence statement Q4
As with their beliefs about the causes and prevention of hepatitis B, people born in countries with intermediate and high endemicity may express beliefs about prevention that are influenced by their personal experiences and cultural background (four [++]). Among people originating from East and South East Asia, prevention strategies may commonly reflect the practice of traditional medicine and vaccination may not generally be considered as a primary means of prevention(five [++] and one [+]). Religious influences on preventive health strategies may also be apparent, for example among Muslim men (one [++]).
Evidence statement Q5
Despite some participants expressing generally positive attitudes towards hepatitis B vaccination and people at high risk being receptive to vaccination (one [++] and one [+]) some studies (two [++] and one [+]) indicated that there is significant confusion and uncertainty surrounding vaccination among groups at a high risk of infection.
Evidence statement Q7
Barriers to testing for hepatitis B include an absence of clear symptoms of infection, practical obstacles such as inconvenience and time constraints, and language and cultural barriers, all of which may discourage some people from seeking care and may limit the role that healthcare providers play in providing education and outreach to immigrant communities (one [++]).
Evidence statement Q8
The perception of hepatitis B as a 'liver' or 'blood' illness rather than a sexually transmitted infection (STI) appears to play an important role in tempering stigma associated with hepatitis B. Increasing awareness of hepatitis B as a sexually transmitted infection was viewed by one study ([++]) as potentially contributing to increased stigma.
Evidence statement Q9
One study ([++]) reported that people with a diagnosis of chronic hepatitis B, including first- and second-generation immigrants, had little recollection of providing consent to test and did not receive adequate information at diagnosis. This lack of information and knowledge was perceived as impacting negatively on their health and preventing opportunities for behaviour change. Both patients and community workers expressed concerns about a lack of provider knowledge with regards to hepatitis B.
Evidence statement Q10
There was evidence that safe and responsible injecting practices are employed by injecting drug users (IDUs) to avoid the transmission of hepatitis C from 6 studies (5 [++] and 1 [+]. There was a lack of consensus as to whether safe practices are strictly adhered to in relation to the sharing of drug related paraphernalia.
Evidence statement Q14
There is strong evidence from 18 studies (eleven [++], five [+], one [-] and one not rated [NR]) that IDUs have an uncertain and incomplete knowledge of hepatitis C. Studies showed that IDUs are confused over what the disease is, how it differs from other forms of hepatitis, how the infection is transmitted and what symptoms are involved. This confusion was reinforced by the perception that expert and scientific knowledge on hepatitis C is shifting and uncertain (three [++] and one [NR]). There is evidence that some IDUs are aware of their limited knowledge of hepatitis C (three [++]).
Evidence statement Q15
Hepatitis C is often understood in relation to HIV in a way that trivialises the seriousness of contracting hepatitis C and may have implications for the use of safe injecting practices and the uptake of hepatitis C services (eleven [++], two [+] and two [NR]).
Evidence statement Q16
A number of barriers to hepatitis C testing among IDUs were identified. People perceiving themselves to be at low risk of hepatitis C infection, a lack of visible symptoms of hepatitis C infection, fear of a positive test result, the use of needles and fear of disclosure were found to prevent the uptake of hepatitis C testing among IDUs (seven [++], eight [+], one [-] and one [NR]). Three studies (two [+] and one [-]) reported barriers to testing specific to the prison setting including long waiting times, lack of information provision, prioritisation of detoxification and withdrawal, and movement between prisons.
Evidence statement Q18
Convenient and opportunistic testing and a 'one-stop shop' approach for all hepatitis C services was regarded as a convenient approach among IDUs (three [++] and five [+]). There is evidence (two [++] and two [+]) that some IDUs were unaware that they had been tested for hepatitis C and concern over informed consent to testing was noted by a number of authors. Although an opportunistic approach can increase testing compliance, a lack of informed consent may also contribute towards uncertain knowledge of hepatitis C among IDUs and limit the impact of testing on behaviour.
Evidence statement Q20
Trust and rapport with healthcare professionals and drug treatment staff motivated people to get tested. Support and encouragement from healthcare professionals also facilitated testing among IDUs (four [+]).
Evidence statement Q21
Studies showed that the experience of being informed about the outcome of hepatitis C testing can be highly confusing (nine [++], two [+], one [-] and one [NR]). Limited and inadequate information provision by healthcare professionals can lead to confusion over the meaning of a positive diagnosis and substantial gaps in knowledge.
Evidence statement Q23
Fear of the adverse effects associated with hepatitis C treatment and the circulation of 'horror stories' and unsuccessful treatment cases among peers discouraged IDUs from engaging with treatment (three [++], one [+] and two [-]). A fear of needles was also common and using needles during the treatment process was a challenge to overcome when considering treatment (two [++] and one [+]). In contrast, anxiety over hepatitis C, witnessing peers suffer from symptoms of hepatitis C infection and hearing stories of successful treatment cases among peers encouraged treatment uptake (two [++] and one [+]).
Evidence statement Q24
Socioeconomic and family circumstances can lead to treatment being de-prioritised among IDUs (three[++] and one [-]). Studies have shown that a preoccupation with drug use, chaotic lifestyles, long waiting times between appointments and employment contributed towards IDUs missing and forgetting treatment appointments, thus increasing the possibility of treatment dropout (three [++]). The assumption of abstinence as a requirement for hepatitis C treatment and continued substance use among IDUs acted as a barrier to treatment (six [++] and one [-]).
Evidence statement Q25
Receiving support from family, partners and peers, starting family life and concerns over the impact of hepatitis C on significant others (for example partners and children) motivated IDUs to engage with hepatitis C treatment (three [++]).
Evidence statement Q27
One study ([-]) found that being in prison was viewed by healthcare professionals as both a barrier and a facilitator for hepatitis C treatment. Transportation of prisoners between prisons and short sentences were viewed as interfering with the treatment process whereas the structured environment of prison and availability of peer support during treatment were regarded as beneficial.
Evidence statement Q28
Two studies found that a lack of access to treatment and a lack of information on treatment options act as barriers to hepatitis C treatment (two [++]). Increasing knowledge of hepatitis C through the provision of information by healthcare professionals encouraged IDUs to consider their treatment options (one [++], two [+] and one [-]).
Evidence statement Q29
The experience of stigma prevented IDUs from seeking hepatitis C testing because of fear of disclosure, and prevented IDUs from disclosing a positive hepatitis C status because of fear of a negative reaction, isolation and social exclusion (eight [++], three [+], one [-] and one [NR]). Stigma also prevented engagement with further prevention education, investigations and treatment and resulted in IDUs receiving inadequate and judgemental care by healthcare professionals (seven [++], six [+], one [-] and two [NR]).
Evidence statement Q30
Perceiving health care professionals to be supportive, concerned and caring, and being encouraged to undertake treatment by healthcare professionals was found to motivate IDUs to engage in hepatitis C treatment (four [++], one [+] and one [-]). There was evidence across a number of studies that IDUs preferred hepatitis C services, including treatment, to be situated in one setting such as drug treatment programmes and methadone substitution settings (two [++] and one [+]). These services were also seen as useful in providing information on hepatitis C treatment (one [++] and three [+]).
Evidence statement E1
There is moderate evidence from three randomised controlled trials (RCTs) (one [++] and two [+]) and one uncontrolled before and after (UBA) study (-) to suggest that providing information and education on hepatitis B to migrant populations may improve their knowledge about risk, screening and prevention; moderate evidence from three RCTs (one [++] and two [+]) to suggest that providing information and education on hepatitis B to migrant populations does not improve testing uptake; and weak evidence from one case series (-) to suggest that testing supplemented with culturally appropriate education may encourage the uptake of follow-up care among migrant populations.
Evidence statement E2
There is moderate evidence from one RCT (+) to suggest that a strategy to promote cancer prevention activities among doctors serving migrant populations does not improve their practices in relation to hepatitis B testing. There is weak evidence from one UBA study (-) to suggest that providing information and education on hepatitis B to complementary and alternative medicine practitioners (including those practising traditional Chinese medicine and acupuncture) may improve their knowledge about risk, screening and prevention. However, the wider impact of this change in knowledge on their practices regarding referral for testing is not clear.
Evidence statement E4
There is moderate evidence from one RCT (+) and one controlled before and after (CBA) study (-) to suggest that offering dried blood spot testing to IDUs attending substance misuse services may increase uptake of hepatitis C testing compared to venepuncture alone being offered. The increase in uptake may reflect an increase in testing availability, as more staff can be trained to deliver dried blood spot testing than venepuncture, as well as higher acceptability to IDUs. There is weak evidence from one case series (CS) study (-) to suggest that providing high-risk groups with access to dried blood spot testing kits via a telephone hotline is not an effective use of resources compared to testing via state laboratories.
Evidence statement E5
There is moderate evidence from one RCT (+) to suggest that although providing GPs with both training and assistance with screening (through the use of patient-targeted materials) may increase patient requests for testing, it does not impact upon the number of patients tested for hepatitis C overall. There is moderate evidence from two non-randomised controlled trials (two [+]) to suggest that targeted case finding in primary care for patients with a history of injecting drug use may have a positive impact on the number of patients who are offered and accept a hepatitis C test. Although the level of referral of patients identified with infection was relatively high, the number of subsequent dropouts prior to treatment indicates that there is a need for further support beyond the intervention offered in these studies.
Evidence statement E6
There is moderate evidence from one RCT (+) and two case series (two [-]) to suggest that providing hepatitis C services in community settings may have a positive impact on testing acceptance and uptake. In particular, there is weak evidence from two case series (two [-]) to suggest that a multidisciplinary or shared care approach to hepatitis C testing and treatment for IDUs is associated with high uptake of follow-up services and treatment outcomes comparable with non-drug-using populations. In two studies conducted in the USA (two [-]), hepatitis testing was added to routine blood work undertaken on entry to drugs services and therefore a high testing rate was inevitable. There is moderate evidence from one RCT (+) to suggest that the provision of testing services via outreach may have a positive impact on testing acceptance and uptake. The impact may be greatest when testing is offered on-site rather than by referral. There is weak evidence from one UBA study (-) to suggest that the provision of hepatitis C outreach services for new prisoners may lead to relatively low uptake of testing.
Evidence statement E7
There is weak evidence from one case series (-) to suggest that offering a non-invasive liver evaluation technique in outreach settings provides an opportunity to subsequently test IDUs for hepatitis C. There is weak evidence from one case series (-) that education by a peer outreach worker may improve short-term knowledge about hepatitis C transmission among IDUs.
Evidence statement E8
There is moderate evidence from one RCT (++), one non-randomised controlled trial (+) and one UBA study (-) to suggest that complex interventions that provide support to primary care professionals when offering hepatitis C testing may have a positive impact on testing acceptance and uptake. One repeated cross-sectional study (+) demonstrated that without support, offers of testing may increase, but not within the desired high-risk groups. There is weak evidence from three UBA studies (three [-]) to suggest that educational interventions aimed at healthcare professionals may have short-term benefits on knowledge about hepatitis C. However, there is no clear evidence that an increase in knowledge leads to an increase in testing. Weak evidence from one UBA study (-) suggested that a continuing medical education programme had a limited impact on testing uptake. There is mixed evidence from two studies (one [++] and one[+]) that examined the effectiveness of interventions aimed at professionals on treatment initiation. There is moderate evidence from a repeated cross-sectional study (+) that a national campaign had no impact on the management of drug users following a positive hepatitis C test. However, there is strong evidence from one RCT (++) that a complex intervention providing support in primary care had a positive impact on number of referrals and attendance at follow-up appointments after testing.
Evidence statement E9
There is weak evidence from one controlled before and after (CBA) study (-) and one case series (-) to suggest that the provision of hepatitis C treatment in community settings for IDUs had a positive effect on treatment initiation and outcomes. There is weak evidence from two case series (both [-]) that attendance at a support group for hepatitis C may have a positive effect on treatment initiation. However, it was unclear due to the study design used whether attendance at the support group was higher among more highly motivated individuals who may have been more likely to initiate treatment regardless of their attendance at the group. There is weak evidence from one cohort study (-) to suggest that allowing patients, such as those who have not been referred by their doctor, to self-refer to speciality liver clinics for assessment was associated with treatment uptake and completion at rates similar to those referred by healthcare professionals. There is weak evidence from a CBA study (-) to suggest that ensuring patients receive education about hepatitis C prior to referral appointments may have a positive effect on attendance at follow-up appointments, and on short to medium-term knowledge.
Evidence statement E11
There is moderate evidence from one cost utility analysis (+) to suggest that community-based screening and treatment for hepatitis B among migrant populations is cost effective.
Additional evidence
A mapping review was also carried out. This was a practice survey of activities and interventions that aim to raise awareness among, and/or engage with, groups who are at an increased risk of hepatitis B and C infection.
Economic modelling
There were three models. One model looked at three scenarios for increasing testing for hepatitis C among people who inject drugs and people who used to inject drugs, with the emphasis on training and education:
-
Training specialist addiction services in the community to undertake dried blood-spot testing for hepatitis C infection.
-
Educating and supporting GPs to identify patients at risk of the infection.
-
Training prison nurses to undertake dried blood-spot testing for hepatitis C infection.
Training for dried blood-spot testing in the community resulted in a substantially greater proportion of cases of hepatitis C infection being identified, compared with not offering this blood sampling method. This led to an estimated cost per quality-adjusted life year (QALY) gained of £15,000, which is below the threshold of £20,000 generally accepted by NICE as cost effective.
Educating GPs about hepatitis C infection and targeted paid testing also resulted in an increase in testing and was also cost effective, yielding an estimated cost per QALY of £14,000. (Clinical administration systems were reviewed to identify registered patients aged 30-54 who had indicators of past injecting drug use. These individuals were offered testing for hepatitis C when they attended the practice for a non-urgent consultation. Practices received £100 remuneration for each test offered). Training prison nurses to undertake dried blood spot testing also increased the proportion of hepatitis C cases found, compared with not offering this sampling method. However, the cost effectiveness of this training depended on whether the resulting treatment was completed. The baseline scenario considered no continuity of care between prison and the community – in which case the cost per QALY of finding a new case was estimated to be £59,000 per QALY and therefore was not cost effective. The estimated cost per QALY of case-finding in prison will be less than £20,000 per QALY gained if there is continuity of care between prison and the community and the treatment rate of people diagnosed in prison is at least 40% of the treatment rate of people diagnosed in the community. Higher treatment rates in the community make prison case-finding more cost effective as long as there is continuity of care.
A second model looked at finding and testing UK migrants for hepatitis C infection. This was found to be cost effective if 2% of the migrant group were infected and it cost no more than £20 to find and test each person. In such a case, the cost per QALY gained was estimated to be £10,000. If the cost of finding and testing someone was £50, the estimated cost per QALY was £18,000. For a given cost of testing, it became more cost effective to find and test people if more than 2% of the population group were infected.
A third model looked at finding and testing UK migrants for chronic hepatitis B. If there was a 2% prevalence within the population group and it cost £20 to find and test each infected person, the estimated cost per QALY gained would be £21,000, marginally above the NICE £20,000 threshold for cost effectiveness. However, it would be cost effective if the prevalence of infection was 3% or higher. At 20% prevalence, as is believed to be the case among some migrant groups, the estimated cost per QALY of finding and testing people falls to £12,000 and was, therefore, deemed cost effective.
Based on the modelling, the PDG considered that it would be cost effective to simultaneously find and test people at risk for both hepatitis B and C, provided there was a 2% prevalence of both infections and it cost up to £75 to find and test each person.