Project Team. David Lewis Leela Barham

Transcription

1 6 th September 2006 Economic of s to Reduce the Transmission of Chlamydia and other Sexually Transmitted and to Reduce the Rate of Under Eighteen Conceptions A Final Report for the National Institute for Health and Clinical Excellence

2 Project Team David Lewis Leela Barham NERA Economic Consulting 15 Stratford Place London W1C 1BE United Kingdom Tel: Fax:

3 Contents Contents 1. Introduction Background Scope Framework Costs Effectiveness Cost Effectiveness Results Accelerated Partner Therapy Patient Referral at GP Clinics Counselling s to Reduce STIs Emergency Contraception Counselling to Prevent Under 18 Conceptions Conceptions Averted Counselling to Prevent Under 18 Conceptions Abortions Summary and Discussion 49 Appendix A. References for Economic 55 Appendix B. Further Incremental Analysis 56 NERA Economic Consulting

4 Contents List of Tables Table 2.1 Good Quality RCTs Identified by Parallel Effectiveness Review on Accelerated Partner Therapy...9 Table 2.2 Incremental Costs for Accelerated Partner Therapy...10 Table 2.3 Incremental Cost Effectiveness Results Accelerated Partner Therapy...11 Table 2.4 Incremental Cost per QALY Results Accelerated Partner Therapy...12 Table 2.5 Threshold Analysis for Proportion in Group to Achieve 20,000 and 30,000 per QALY - Accelerated Partner Therapy...13 Table 2.6 Threshold Analysis for Unit Cost to Achieve 20,000 and 30,000 per QALY- Accelerated Partner Therapy...13 Table 2.7 Good Quality RCT Identified by Parallel Effectiveness Review on Patient Referral at GP Clinics..18 Table 2.8 Costs of Partner Notification Strategies in Primary Care...19 Table 2.9 Good Quality RCTs Identified by Parallel Effectiveness Review on Counselling to Reduce STIs...20 Table 2.10: Incremental Costs for Counselling to Reduce STIs...23 Table 2.11 Incremental Cost Effectiveness Results Counselling to Reduce STIs...25 Table 2.12 Incremental Cost per QALY Results Counselling to Reduce STIs...27 Table 2.13 Threshold Analysis for Time Spent to Achieve 20,000 and 30,000 per QALY Counselling to Reduce STIs...29 Table 2.14 Threshold Analysis for Unit Cost to Achieve 20,000 and 30,000 per QALY Counselling to Reduce STIs...30 Table 2.15 Threshold Analysis for Proportion in With STIs to Achieve 20,000 and 30,000 per QALY Counselling to Reduce STIs...31 Table 2.16 Comparison of Study Rates and Rates in England, Gonorrhoea for General English Population and for Year Old English Population...36 Table 2.17 Comparison of Study Rates and Rates in England, Chlamydia for General English Population and for Year Old English Population...38 Table 2.18 Good Quality RCTs Identified by Parallel Effectiveness Review on Emergency Contraception...41 Table 2.19 Incremental Costs for Emergency Contraception...42 Table 2.20 Incremental Cost Effectiveness Results Emergency Contraception...42 Table 2.21 Good Quality RCT Identified by Parallel Effectiveness Review on Counselling to Reduce Under 18 Conceptions...44 Table 2.22 Incremental Costs for Counselling to Reduce Under 18 Conceptions...45 Table 2.23 Incremental Cost Effectiveness Results Counselling to Reduce Under 18 Conceptions...45 Table 2.24 RCT Identified by Parallel Effectiveness Review on Counselling to Reduce Under 18 Conceptions Abortions...47 Table 2.25 Incremental Costs for Counselling to Reduce Under 18 Conceptions...48 Table 2.26 Incremental Cost Effectiveness Results Counselling to Reduce Under 18 Conceptions - Abortions...48 Table 3.1 Incremental Costs, Outcomes and Incremental Cost Effectiveness Ratios of s to Tackle STIs...51 Table 3.2 Incremental Costs and Cost Effectiveness Ratios for s to Reduce Under 18 Conceptions per 1,000 People...53 NERA Economic Consulting

5 Contents List of Figures Figure 1.1 Rates of Diagnosis of Uncomplicated Genital Chlamydial Infection by Sex and Age Group, GUM Clinics, United Kingdom, 1995 to Figure 1.2 Under 18 Conception Rate, England, 1998 to Figure 2.1 Static Decision Tree...5 Figure 2.2 Sensitivity to QALY Decrement, Cost per QALY, QALY Decrement 0.01 to 1 Accelerated Partner Therapy...14 Figure 2.3 Sensitivity to QALY Decrement, Up to 30,000 per QALY, QALY Decrement 0.01 to Accelerated Partner Therapy...15 Figure 2.4 Sensitivity to QALY Decrement, Up to 20,000 per QALY, QALY Decrement 0.01 to Accelerated Partner Therapy...16 Figure 2.5 Sensitivity to QALY Decrement, Cost per QALY, QALY Decrement 0.01 to 1 Counselling to Reduce STIs...33 Figure 2.6 Sensitivity to QALY Decrement, Up to 30,000 per QALY, QALY Decrement 0.01 to 1 Counselling to Reduce STIs...34 Figure 2.7 Sensitivity to QALY Decrement, Up to 20,000 per QALY, QALY Decrement 0.01 to 1 Counselling to Reduce STIs...35 Figure 3.1 Costs and Averted for s to Reduce STIs per 1,000 People...53 Figure 3.2 Costs and Averted for s to Reduce s...54 NERA Economic Consulting

6 Introduction 1. Introduction 1.1. Background NERA Economic Consulting was commissioned by the National Institute for Health and Clinical Excellence (NICE) to undertake primary cost effective analysis of selected one to one interventions to tackle STIs and teenage conceptions. This modelling is required as one input into the development of recommendations by the Public Health s Advisory Committee (PHIAC) on interventions to tackle STIs and teenage conceptions. This modelling is conducted against a background of rising incidence of STIs, in particular a sharp increase in Chlamydia (Figure 1.1). Figure 1.1 Rates of Diagnosis of Uncomplicated Genital Chlamydial Infection by Sex and Age Group, GUM Clinics, United Kingdom, 1995 to 2004 Rate per 100,000 population Males < > Females HPA Using: KC60 statutory returns and ISD(D)5 data. The rise in incidence in STIs is also likely to lead to increased numbers incidence of complications. Complications include pelvic inflammatory disease (PID), ectopic pregnancy and infertility (although it should be noted that these conditions can occur independently from STIs). We did not locate information on the incidence of complications in the UK. Recent evidence from Sweden (Low et al 2006) suggests that in the case of Chlamydia: Given a positive test for Chlamydia 5.6 per cent of women suffer from PID, with a negative test the corresponding figure is 2.6 per cent, and 2.9 per cent in those never screened; Given a positive test for Chlamydia 2.7 per cent of women suffer from PID, with a negative test the corresponding figure is 2.0 per cent, and 1.9 per cent in those never screened; and NERA Economic Consulting 1

7 Introduction Given a positive test for Chlamydia 6.7 per cent of women suffer from PID, with a negative test the corresponding figure is 4.7 per cent, and 3.1 per cent in those never screened. These rates are lower than have been seen in other studies and than assumptions used in some economic studies. For example, Low et al (2006) note that their study estimates that the incidence of hospital diagnosed PID is 1.9 per 1,000 woman years compared to rates as high as 5 to 7 per 1,000 woman years and per 1,000 woman years in primary care. Some experts have also suggested that improvements in testing mean that tests may be detecting less serious cases of Chlamydia. 1 We did not locate information on the cost of treating complications but the impact appears likely to be of significant both on patients, and also the NHS as a whole. There is a need to focus on those interventions which offer the best outcomes at an acceptable cost. The analysis is also conducted against the background of the Teenage Pregnancy Strategy targets to: Reduce by 50 per cent the 1998 England under 18 conception rate by 2010, with an interim target of a 15 per cent reduction by 2004; Achieve a well established downward trend in the under 16 conception rate by 2010; Reduce the inequality in rates between the fifth of wards with the highest under 18 conception rate and the average ward rate by at least 25 per cent by 2010; and Increase to 60 per cent the participation of teenage parents in education, training or employment to reduce their risk of long-term social exclusion by The rate of under 18 conceptions has been falling over time (Figure 1.2) Personal Communication to NERA from Helen Ward NERA Economic Consulting 2

8 Introduction Figure 1.2 Under 18 Conception Rate, England, 1998 to Under 18 conception rate per Year Source: Office for National Statistics and Teenage Pregnancy Unit, 2006 Rate per thousand females aged As with STIs there is a need to consider which interventions work at an acceptable cost to contribute to the achievement of these targets and to sustain the reductions in teenage pregnancies seen in recent years. This report does not consider the budget implications of implementing PHIAC recommendations but we note that clinical experts have raised concerns about the available resources for tackling STIs. 2 In particular it has been noted that current practice is variable and that there is a focus on brief interventions in GUM clinics. For this reason we consider the costs of counselling interventions studied in the literature as being incremental to current practice. We note that the view that there are constraints in tackling STIs on the ground is reinforced by survey work by British HIV Association, Providers of AIDS Care & Treatment and Terrence Higgins Trust which suggests that money intended for the improvement of sexual health services is not reaching the intended target (British HIV Association, Providers of AIDS Care & Treatment and Terrance Higgins Trust 2006). These issues increase the importance of identifying the most cost-effective use of resources Scope As requested by NICE we have focused on developing a simple cost-effectiveness model drawing upon the data from the parallel effectiveness reviews. These reviews focus on one to one interventions such as counselling and advice (excluding screening) and partner notification. We note that the majority of studies in the effectiveness reviews highlight intermediate outcomes (e.g. uptake of emergency contraception, knowledge of STIs), a limited number look at final outcomes (such as conceptions, re-infections) and none include 63 2 Personal Communication to NERA from Helen Ward NERA Economic Consulting 3

9 Introduction outcome measures such as QALYs or life years. This places some limits on the scope of modelling that can be undertaken. We have not included further modelling for Chlamydia screening as requested by NICE. We also note that the effectiveness reviews have not included screening for any other STIs and so we have not included further modelling on screening for other diseases. Rather, as discussed with NICE we have focused on economic considerations associated with the interventions where the clinical evidence reviews have found the strongest evidence of effectiveness. We look in more detail at the following interventions: Accelerated partner therapy; Patient referral; Counselling interventions to reduce STIs; Emergency contraception; and Counselling interventions to reduce teenage conceptions. These interventions have been selected for further economic modelling on the basis that: There are effectiveness studies rated at least + or ++ which means that the economic modelling can be based on better quality effect data; and There are effectiveness studies that provide final outcomes (which are also rated + or ++) rather than intermediate outcomes (a number of assumptions would be required to link intermediate outcomes to final outcomes and there is little data available to support such assumptions). NERA Economic Consulting 4

10 Framework We have undertaken simple modelling to illustrate the costs and outcomes of interventions to tackle STIs and teenage conceptions. Our model can be explained as the initial stages of a static decision tree, as shown in Figure 2.1. Figure 2.1 Static Decision Tree Infection/Pregnant P i (o) Given intervention Ideally outcomes would also incorporate: Population C i No infection/pregnancy P i (no) -Further health care interventions (e.g. hospitalisation and treatments of complications) Infection/Pregnant -Impact on quality of life (e.g. QALY) P c (o) - Dynamic impacts Not given intervention C c No infection/pregnant Source: NERA P c (no) Where: Ci Cc is the incremental cost of delivering the intervention; Pi (o) is the probability of the intervention group having an outcome such as an STI or being pregnant (or partner being pregnant), Pi (no) is the probability of the intervention group not having the outcome. Estimates of the probability are generally derived from the proportion in the group having the outcome of interest in effectiveness studies as reported in Bunn et al (2006), Low et al (2006) and Trelle et al (2006) provided to us by NICE; and Pc (o) is the probability of the control group having an outcome such as an STI or being pregnant (or partner being pregnant), Pc (no) is the probability of the control group not having the outcome. These are derived from the proportions in the group having the outcome of interest in effectiveness studies as reported in Bunn et al (2006), Low et al (2006) and Trelle et al (2006) provided to us by NICE.. This simple model can be extended by assigning cost and health impact outcomes to the intermediate outcomes noted. Wider outcomes could include factors such as complications NERA Economic Consulting 5

11 of having the infection, and the impact on quality of life. However given, limited time and resources for modelling and a lack of data significant progress is difficult. One particularly useful approach is to assign QALY states to the outcomes studied. We note that in the Harvard Cost Effectiveness Analysis Register there are QALY states for HIV (ranging from values of 0.2 for poor health status with HIV/AIDS to 1 for HIV infection for the first 6 years). However, there are no QALY estimates for other STIs. We also note that our own rapid economic review found only 1 study (Hu 2004) which used cost per QALY that was not focused on HIV/AIDS. Hu (2004) used a QALY weight of 0.90 for symptomatic acute urogenital chlamydial infection, 0.65 for symptomatic acute pelvic inflammatory disease, 0.60 for chronic pelvic pain, 0.58 for ectopic pregnancy, and 0.82 for tubal infertility in a cost effectiveness analysis of Chlamydia screening in women aged 15 to 29 years old. No studies provided QALYs for other STIs or for having a generic STI. This is particularly problematic given that an outcome commonly used in studies considered in the parallel effectiveness review is based around generic STIs. Where possible we have indicated the cost of health care interventions that can be avoided, (the cost of normal delivery for pregnancies avoided). We do not include wider benefits, such as societal costs avoided from the reduction in unintended pregnancies. We note that other guidance has also not included these benefits (see National Collaborating Centre for Women s and Children s Health (2005)). We also do not consider the long-term costs and consequences avoided arising from raising a child born as a result of an unintended pregnancy. As the National Collaborating Centre for Women s and Children s Health (2005) notes, it would be necessary to consider both the future costs and benefits for the evaluation to be meaningful, and no straightforward and satisfactory way of identifying and measuring the future costs and benefits to society is currently available. Throughout we have assumed that costs and benefits occur in the same single year. We note that most effectiveness studies follow up for a year or less. Given the infectious nature of STIs it is difficult to know whether the benefits will be sustained for longer periods. Given our assumption of costs and benefits occurring in the same single year we do not need to include discounting in our analysis. The analysis is conducted on a static basis. Dynamic effects - such as additional benefit deriving from reduced onward transmission once an infection is identified are not considered Costs We built up cost estimates of delivering interventions based upon the resource use identified in the effectiveness studies as reported in Bunn et al (2006), Low et al (2006) and Trelle et al (2006) provided to us by NICE. This typically consisted of: Health care professional time. This reflects the additional time spent delivering the intervention compared to standard practice as identified in the study. We include delivery by different types of health care professional including GPs and practice nurses. Unit costs were taken from PSSRU (2005) Unit Costs of Health and Social Care and are for financial year 2004/5. NERA Economic Consulting 6

12 Treatment. This reflects the additional treatment provided as a result of the intervention compared to standard practice as identified in the study. Unit costs were taken from Drug Tariff, March Information. This reflects additional sources of information, such as leaflets, provided in the intervention compared to standard practice as identified in the study. We use the unit cost of 4 per person in the intervention group taken from Matrix (2005). We include the English Department of Health s National Tariff 2005/6 value for normal delivery for the health care costs avoided from reduced conceptions as an indicator of costs avoided in the NHS. We do not adjust any costs as they are from close years and inflating costs would have little overall impact on values used in our analysis. Our analysis focuses on the direct costs of providing the relevant intervention. It does not include costs as training or overheads, which might in principle be relevant. However, if interventions were rolled out training costs would be a smaller part of average costs of delivering the interventions. The incremental cost would reflect additional staff time and this is our focus in our modelling. Overhead costs become more important where capacity constraints require increasing open times at clinics etc. The situation regarding this is unclear although suggestions of existing pressure on services means it could be an issue. However, in our simple modelling we have not included them Effectiveness The measure of effect was taken as the difference between outcomes seen in the intervention group and the control group as reported in Bunn et al (2006), Low et al (2006) and Trelle et al (2006) provided to us by NICE.. As agreed with NICE we drew only on studies receiving a + or ++ rating in the parallel effectiveness review. Whilst ideally we would apply the difference between intervention and control group outcomes to population outcomes in England and Wales we have been limited by the availability of data. For example, currently data is collected on individual infections (e.g. Chlamydia) and not on individuals with infections or who are reinfected. We have therefore used the proportions in the outcome and control group with no adjustments in our calculations of cost effectiveness. This assumes that the underlying characteristics of study participants in effectiveness studies are similar to the English and Welsh population Cost Effectiveness Results Accelerated Partner Therapy Effect Two RCTs were identified by the effectiveness review of partner notification which assessed the impact of accelerated partner therapy which received a + rating. This intervention is defined as treatment of partner(s) of index patients without an intervening personal assessment by a health care provider. Accelerated partner therapy can be implemented in NERA Economic Consulting 7

13 several ways. Usually, physicians provide index patients with drugs or prescriptions intended to be delivered to the partner(s). (Trelle et al 2006) Information on the intervention, outcomes used and effects is outlined in Table 2.1. NERA Economic Consulting 8

14 Table 2.1 Good Quality RCTs Identified by Parallel Effectiveness Review on Accelerated Partner Therapy Study Infection type Control Outcome Control Effect estimate Quality rating Golden et al (2005) Gonorrhoea or Chlamydia Accelerated partner therapy Patient referral Proportion of index patients free of persistent or recurrent infection Proportion with all partners treated Partners elicited Schillinger et al (2003) Chlamydia Accelerated partner therapy Patient referral Patients free of persistent or recurrent infection Source: Abstracted from Trelle et al (2006). ITT results for Schillinger et al (2003). Numbers for control, intervention and effect are probabilities. These are derived from the proportions of the control and intervention groups who report each outcome. NERA Economic Consulting 9

15 Incremental Costs The cost of delivering accelerated partner therapy reflects the provision of prescriptions and patient information (such as leaflets). We have not included the cost of diagnosis and health care professional time because these costs would be incurred in the absence of the intervention. The costs for accelerated partner therapy for Golden et al (2005) and Schillinger et al (2003) are set out in Table 2.2. We use two costs for prescriptions, azithromycin as used in the study and also doxyclycline which is listed in the British National Formulary as an option for treating STIs. Table 2.2 Incremental Costs for Accelerated Partner Therapy Study Medicines Information Incremental Cost Per Person Golden et al (2005) vs. patient referral Max 3 * azithromycin@ 8.95 = Max 3 * leaflet@ 4 = 12 Max Max 3 * doxycycline@ 5.35 = Max 3 * leaflet@ 4 = 12 Max Schillinger et al (2003) vs. patient referral Max 4 * azithromycin@ 8.95 = Max 4 * leaflet@ 4 = 16 Max Max 4* doxycycline@ 5.35 = Max 4 * leaflet@ 4 = 16 Max Source: NERA. Notes: Unit cost of azithromycin based on four 250mg capsules at 8.95 from the Drug Tariff March Note we have focused on treatment for Chlamydia in Golden et al (2005). Unit cost of doxycycline based on calendar pack at 5.35 from the Drug Tariff March Incremental Cost Effectiveness Ratios A comparison of the incremental costs and incremental benefits based on a cohort of 1,000 patients receiving the intervention and 1,000 patients not receiving accelerated partner therapy is provided in Table 2.3. NERA Economic Consulting 10

16 Table 2.3 Incremental Cost Effectiveness Results Accelerated Partner Therapy Study Incremental Cost for 1,000 People Receiving the Incremental Reinfections Averted for 1,000 People Receiving the Incremental Cost per Reinfection Averted Golden et al (2005) azithromycin vs. patient referral Golden et al (2005) doxyclycline vs. patient referral Schillinger et al (2003) azithromycin vs. patient referral Schillinger et al (2003) doxyclycline vs. patient referral 38, ,295 28, , ,590 37, ,870 Source: NERA Incremental Cost per QALY We have undertaken some extensions to the simple cost effectiveness model to look at the potential cost per QALYs obtained through the interventions. Although cost per QALY is an outcomes that facilitates comparison between disparate interventions, if is important to note that it is subject to various difficulties in this context, especially due to highly limited data on QALY outcomes. In particular several potentially controversial assumptions are required: We are assuming that the reinfection has the same impact on quality of life as Chlamydia (the only STI excluding HIV/AIDS where there are published estimates of QALY states identified in our rapid economic review); We are assuming that all those who are reinfected have symptoms; We are assuming that all those who are reinfected do not go on to have complications from Chlamydia; and We are assuming that all those who are reinfected have reduced quality of life for a year. We also note that the vast majority of studies identified by either the rapid economic review or the effectiveness review do not use QALYs as an outcome measure. We use the QALY weight of 0.90 for symptomatic acute urogenital chlamydial infection used in Hu (2004). However the study does not provide detail on how this estimate is derived of precisely what is covered. This is equivalent to assuming that the health impact on an individual sustained through an STI infection is on average equivalent to the loss around one NERA Economic Consulting 11

17 month s life in perfect health. We tested these assumptions with professionals and while they could not be endorsed as robust, there was no reasons to change the estimates in a particular direction. Table 2.4 Incremental Cost per QALY Results Accelerated Partner Therapy Study Incremental Cost for 1,000 People Receiving the Incremental QALYs Gained for 1,000 People Receiving the Incremental Cost per QALY Golden et al (2005) azithromycin vs. patient referral Golden et al (2005) doxyclycline vs, patient referral Schillinger et al (2003) azithromycin vs. patient referral Schillinger et al (2003) doxyclycline vs. patient referral 38, ,950 28, ,350 51, ,900 37, ,700 Source: NERA. Hence, on the basis of the assumptions above, accelerated partner therapy results in a cost per QALY range from 9,350 to 25,900, depending largely on the source clinical data used Sensitivity Analysis We undertook a range of sensitivity analysis, focusing upon the threshold values that needed to be used in order to achieve particular cost per QALY values. NICE asked us to focus on a 20,000 per QALY value, and we also looked at a 30,000 per QALY value. We calculate the level of costs and the proportion with STIs in the intervention group that is required (in each case holding other parameters constant) for the cost per QALY to be at each specific level. The following tables illustrate our results. We also undertake sensitivity analysis which examines how the incremental cost per QALY ratio alters as the level of QALY decrement assumed to relate to infection alters, and we present this in that form. NERA Economic Consulting 12

18 Table 2.5 Threshold Analysis for Proportion in Group to Achieve 20,000 and 30,000 per QALY - Accelerated Partner Therapy Study Cost per QALY Proportion in Group to Achieve 20,000 per QALY Proportion in Group to Achieve 30,000 per QALY Golden et al (2005) azithromycin Golden et al (2005) - doxyclycline Schillinger et al (2003) azithromycin Schillinger et al (2003) doxyclycline 12, , , , Source: NERA. Table 2.6 Threshold Analysis for Unit Cost to Achieve 20,000 and 30,000 per QALY- Accelerated Partner Therapy Study Cost per QALY Unit Cost Unit Cost to Achieve 20,000 per QALY Unit Cost to Achieve 30,000 per QALY Golden et al (2005) azithromycin Golden et al (2005) - doxyclycline Schillinger et al (2003) azithromycin Schillinger et al (2003) doxyclycline 12, , , , Source: NERA. NERA Economic Consulting 13

19 Figure 2.2 Sensitivity to QALY Decrement, Cost per QALY, QALY Decrement 0.01 to 1 Accelerated Partner Therapy 300, ,000 Cost per QALY 200, , ,000 50, Golden APT A Golden APT D Schillinger APT A Schillinger APT D QALY Decrement Source: NERA. NERA Economic Consulting 14

20 Figure 2.3 Sensitivity to QALY Decrement, Up to 30,000 per QALY, QALY Decrement 0.01 to Accelerated Partner Therapy 30,000 25,000 Cost per QALY 20,000 15,000 10,000 5, Golden APT A Golden APT D Schillinger APT A Schillinger APT D QALY Decrement Source: NERA. NERA Economic Consulting 15

21 Figure 2.4 Sensitivity to QALY Decrement, Up to 20,000 per QALY, QALY Decrement 0.01 to Accelerated Partner Therapy 20,000 18,000 16,000 Cost per QALY 14,000 12,000 10,000 8,000 6,000 4,000 2,000 - Golden APT A Golden APT D Schillinger APT A Schillinger APT D QALY Decrement Source: NERA. We find that accelerated partner therapy, based on our assumptions, can achieve a cost per QALY within 30,000 in the base case. Based on most clinical assumptions a cost per QALY within 20,000 is achieved. Azithromycin in the Schillinger (2003) study would need only a very small increase in effectiveness (a further 1 per cent reduction in infections in the intervention group) to reach a 20,000 per QALY threshold. The value of the QALY decrement is particularly important in this analysis. At low levels of decrement the cost per QALY increases, but at around 0.1 decrement accelerated partner therapy is within cost per QALY thresholds as described above Patient Referral at GP Clinics Effect One good quality RCT was identified by the effectiveness review of partner notification which assessed the impact of patient referral at GP clinics versus patient referral at GUM clinics. Patient referral at GP clinics is described by Trelle et al (2006) as patient notification by a trained practice nurse including sexual history for last 6 months, patient referral using contact slips (contact details of GUM plus request for GUM to return the slip to study centre), advice regarding NERA Economic Consulting 16

22 abstinence until partner completed therapy, information about being screened for other STIs and telephone follow-up by a health advisor. This was compared to partner notification at GUM clinic. This is described as provision of contact details of health adviser at GUM clinic. If there was no contact at the GUM within 1 week this led to 2 attempts to contact the partner by the health advisor. The advisor carried out partner notification according to standard protocols either as patient referral, provider referral, or conditional referral plus contact slips and offered screening for other STIs and telephone follow up by a health advisor. NERA Economic Consulting 17

23 s to Reduce STIs and Table 2.7 Good Quality RCT Identified by Parallel Effectiveness Review on Patient Referral at GP Clinics Study Infection type Outcome Control Effect estimate Quality rating Low et al (2005) Chlamydia Patient referral at GP Partners treated Proportion with all partners treated Proportion with at least one partner treated Partners elicited Source: Abstracted from Trelle et al (2006) NERA Economic Consulting 18

24 Cost Low et al (2005) includes the cost of providing patient referral in both GP practices and GUM clinics. Table 2.8 provides details on the costs. Table 2.8 Costs of Partner Notification Strategies in Primary Care Practice nurse strategy Genitourinary medicine clinic Index case treatment Mean (95% CI) partner notification advice: No of participants Unit cost Total No of participants Unit cost Total At GP practice (10.37 to 13.08) (9.74 to 11.98) At clinic Partner treatment Mean (95% CI) cost per index case (31.20 to 33.91) (31.49 to 33.73) Source: Low et al (2005). Notes: costs in United Kingdom sterling in 2003 prices. Cost of nurse per hour, health adviser per hour, azithromycin assumed to have been used for all index cases and sexual partners. Costs include time for giving treatment, explaining study, gaining consent, and explaining referral process to genitourinary medicine clinic for all 68 index cases. Costs also include time for health advisor consultation for 47 index cases who attended the genitourinary medicine clinic. Low et al s own analysis suggests that partner notification by a practice nurse at a general practice was the dominant option as it cost the same as the GUM setting but achieved a higher number of treated patients Counselling s to Reduce STIs Effect We draw on the RCTs that were identified by the effectiveness review which assessed the impact of different types of counselling interventions to reduce STIs which received a + and a ++ rating. Two of these found no difference in infections and so we do not use these studies for further modelling. Information on the intervention, outcomes used and effect are outlined in Table 2.9. NERA Economic Consulting 19

25 s to Reduce STIs and Table 2.9 Good Quality RCTs Identified by Parallel Effectiveness Review on Counselling to Reduce STIs Study Infection type Control Outcome Control Effect estimat e Kamb (1998) Any STIs Brief counselling Didactic messages - information al intervention designed to approximate treatment as usual Kamb (1998) Any STIs Enhanced counselling Didactic messages - information al intervention designed to approximate treatment as usual Quality rating New STI New STI Maher (2003) Any STIs Intensive counselling Treatment as usual Definite STI Metcalf (2005) Any STIs Counselling Not stated Any STI Boyer (1997) Any STIs Behavioural skills counselling Standard 15 minute risk-reduction counselling STI Downs (2004) Any STIs Counselling Not stated Any STI Kalichman (2005) Any STIs Information and motivation (men) Information only delivered by counsellors in didactic style Kalichman (2005) Any STIs Information and motivation (women) Information only delivered by counsellors in didactic style Kalichman (2005) Any STIs Information and behaviour skills (men) Information only delivered by counsellors in didactic style Kalichman (2005) Any STIs Information and behaviour skills (women) Kalichman (2005) Any STIs Information, motivation and behaviour skills (men) Kalichman (2005) Any STIs Information, motivation and behaviour skills (women) Information only delivered by counsellors in didactic style Information only delivered by counsellors in didactic style Information only delivered by counsellors in didactic style New STI New STI New STI New STI New STI New STI Scholes (2003) Any STIs Counselling Not stated STI Bolu (2004) Any STIs Enhanced counselling Didactic messages - information al intervention designed to approximate treatment as usual STI * ++ Bolu (2004) Any STIs Brief counselling Didactic messages - information al intervention designed to approximate treatment as usual STI NERA Economic Consulting 20

26 s to Reduce STIs and Study Infection type Control Outcome Control Effect estimat e James (1998) Any STIs Tailored skill session Standard clinic session with health advisor Reattendance at clinic with new STI James (1998) Any STIs Tailored skill session Standard clinic session with health advisor + leaflet and condom pack Reattendance at clinic with new STI Quality rating Source: Abstracted from Bunn et al (2006). denotes intervention better than control. Rounding affects numbers presented. Numbers for control, intervention and effect are probabilities. These are derived from the proportions of the control and intervention groups who report each outcome. NERA Economic Consulting 21

27 Incremental Costs The cost of counselling sessions reflects the time and staff delivering the intervention. We have used a practice nurse as a proxy for the cost of staff used in the studies described in the effectiveness reviews. We leave out those studies where we did not have cost information. The issue arises of whether these counselling costs are wholly, partly, or not at all incremental in current practice. Current practice is not well documented (whether in the English and Welsh context, or what it means in practice as a comparator in the studies). Discussions with experts suggested that it is in practice quite variable. However, increasing pressures on resources make it likely that time available for counselling is being squeezed in order to increase user throughput. On this basis we assume that costs of delivering counselling are all incremental costs. We note that this does, however, risk underestimating the cost-effectiveness of counselling interventions. NERA Economic Consulting 22

28 s to Reduce STIs and Table 2.10: Incremental Costs for Counselling to Reduce STIs Study Control Type of Staff Delivering Kamb (1998) Enhanced counselling Didactic messages - informational intervention designed to approximate treatment as usual Kamb (1998) Brief counselling Didactic messages - informational intervention designed to approximate treatment as usual Time (hrs) Unit Cost Incremental Cost Per Person Practice nurse Practice nurse Maher (2003) Intensive counselling Treatment as usual Practice nurse Boyer (1997) Behavioural skills counselling Standard 15 minute risk-reduction counselling Practice nurse Kalichman (2005) Information and motivation (men) Information only delivered by counsellors in didactic style Practice nurse * Kalichman (2005) Kalichman (2005) Kalichman (2005) Kalichman (2005) Kalichman (2005) Information and motivation (women) Information and behaviour skills (men) Information and behaviour skills (women) Information, motivation and behaviour skills (men) Information, motivation and behaviour skills (women) Information only delivered by counsellors in didactic style Information only delivered by counsellors in didactic style Information only delivered by counsellors in didactic style Information only delivered by counsellors in didactic style Information only delivered by counsellors in didactic style Practice nurse * Practice nurse * Practice nurse * Practice nurse * Practice nurse * James (1998) Tailored skill session Didactic messages - informational intervention Practice nurse designed to approximate treatment as usual Bolu (2004) Enhanced counselling Didactic messages - informational intervention Practice nurse designed to approximate treatment as usual Bolu (2004) Brief counselling Standard clinic session with health advisor Practice nurse James (1998) Tailored skill session Didactic messages - informational intervention designed to approximate treatment as usual Practice nurse Source: NERA. Notes: Unit costs based on PSSRU (2005) Unit Costs of Health and Social Care. * In this study the time to deliver any combination of the intervention was the same. We have included the cost for completeness. Cost presented to nearest whole 1. NERA Economic Consulting 23

29 Incremental Cost Effectiveness Ratios A comparison of the incremental costs and incremental benefits based on a cohort of 1,000 patients receiving the intervention and 1,000 patients not receiving counselling is provided in Table NERA Economic Consulting 24

30 s to Reduce STIs and Table 2.11 Incremental Cost Effectiveness Results Counselling to Reduce STIs Study Control Incremental Cost for 1,000 People Receiving the Incremental STI Averted for 1,000 People Receiving the Incremental Cost per STI Infection Averted Kamb (1998) Enhanced counselling Didactic messages - informational 160, ,161 intervention designed to approximate treatment as usual Kamb (1998) Brief counselling Didactic messages - informational 32, ,231 intervention designed to approximate treatment as usual Maher (2003) Intensive counselling Treatment as usual 96, ,400 Boyer (1997) Kalichman (2005) Kalichman (2005) Kalichman (2005) Behavioural skills counselling Information and behaviour skills (women) Information, motivation and behaviour skills (men) Information, motivation and behaviour skills (women) Standard 15 minute risk-reduction counselling Information only delivered by counsellors in didactic style Information only delivered by counsellors in didactic style Information only delivered by counsellors in didactic style 192, ,600 72, ,029 72, ,800 72, ,029 Bolu (2004) Enhanced counselling Didactic messages - informational 158, ,960 intervention designed to approximate treatment as usual Bolu (2004) Brief counselling Didactic messages - informational 32, ,208 intervention designed to approximate treatment as usual James (1998) Tailored skill session Standard clinic session with health advisor 16, Source: NERA. In Kalichman (2005) in 3 subgroups the had more STIs than the control, these include: information and motivation (men), information and motivation (women), information and behaviour skills (men). We do not include these in our estimates of cost effectiveness to reduce STIs. Numbers may not sum due to rounding. Costs presented to nearest whole 1. NERA Economic Consulting 25

31 Incremental Cost per QALY As before, we have undertaken some extensions to the simple cost effectiveness model to look at the potential impact on QALYs. It is important to note several assumptions in doing this including the reinfection having the same impact on quality of life as Chlamydia, those who are reinfected have symptoms but no further complications, and reduced quality of life for a year. As before, we use the QALY weight of 0.90 for symptomatic acute urogenital chlamydial infection used in Hu (2004). Results are shown in Table Further incremental analyses undertaken by NICE are shown in Appendix B. NERA Economic Consulting 26

32 s to Reduce STIs and Table 2.12 Incremental Cost per QALY Results Counselling to Reduce STIs Study Control Incremental Cost for 1,000 People Receiving the Kamb (1998) Enhanced counselling Didactic messages - informational intervention designed to approximate treatment as usual Kamb (1998) Brief counselling Didactic messages - informational intervention designed to approximate treatment as usual Incremental STI Averted for 1,000 People Receiving the Incremental QALYs gained for 1,000 People Receiving the Incremental cost per QALY gained 160, ,613 32, ,308 Maher (2003) Intensive counselling Treatment as usual 96, ,000 Boyer (1997) Behavioural skills counselling Standard 15 minute riskreduction counselling Kalichman (2005) Kalichman (2005) Kalichman (2005) Information and behaviour skills (women) Information, motivation and behaviour skills (men) Information, motivation and behaviour skills (women) Information only delivered by counsellors in didactic style Information only delivered by counsellors in didactic style Information only delivered by counsellors in didactic style Bolu (2004) Enhanced counselling Didactic messages - informational intervention designed to approximate treatment as usual Bolu (2004) Brief counselling Didactic messages - informational intervention designed to approximate treatment as usual James (1998) Tailored skill session Standard clinic session with health advisor Source: NERA. Numbers may not sum due to rounding. Costs presented to nearest whole , ,000 72, ,286 72, ,000 72, , , ,600 32, ,080 16, ,200 NERA Economic Consulting 27

33 Sensitivity Analysis We undertook a range of sensitivity analysis, focusing upon the threshold values that needed to be used in order to achieve particular cost per QALY values. NICE asked us to focus on a 20,000 per QALY value, and we also looked at a 30,000 per QALY value. We calculate the value of time input, unit cost, and proportion with STIs in the intervention group that is required (in each case holding other parameters constant) for the cost per QALY to be at each specific level. The following tables illustrate our results. NERA Economic Consulting 28

34 Table 2.13 Threshold Analysis for Time Spent to Achieve 20,000 and 30,000 per QALY Counselling to Reduce STIs Study Control Cost per QALY Base case Time (hrs) Base case Time Spent to Achieve 20,000 per QALY Time Spent to Achieve 30,000 per QALY Kamb (1998) Enhanced counselling Not stated 51, Kamb (1998) Brief counselling Didactic messages - informational intervention designed to approximate treatment as usual Maher (2003) Intensive counselling Didactic messages - informational intervention designed to approximate treatment as usual 12, , Boyer (1997) Behavioural skills counselling Not stated 96, Kalichman (2005) Information and behaviour skills (women) Kalichman (2005) Information, motivation and behaviour skills (men) Kalichman (2005) Information, motivation and behaviour skills (women) Not stated 10, Information only delivered by counsellors in didactic style Information only delivered by counsellors in didactic style Bolu (2004) Enhanced counselling Didactic messages - informational intervention designed to approximate treatment as usual Bolu (2004) Brief counselling Didactic messages - informational intervention designed to approximate treatment as usual James (1998) Tailored skill session Standard clinic session with health advisor Source: NERA Analysis 18, , , , , NERA Economic Consulting 29

35 Table 2.14 Threshold Analysis for Unit Cost to Achieve 20,000 and 30,000 per QALY Counselling to Reduce STIs Study Control Cost per QALY Base case Unit Cost Base case Unit Cost to Achieve 20,000 per QALY Unit Cost to Achieve 30,000 per QALY Kamb (1998) Enhanced counselling Not stated 51, Kamb (1998) Brief counselling Didactic messages - informational intervention designed to approximate treatment as usual Maher (2003) Intensive counselling Didactic messages - informational intervention designed to approximate treatment as usual 12, , Boyer (1997) Behavioural skills counselling Not stated 96, Kalichman (2005) Information and behaviour skills (women) Kalichman (2005) Information, motivation and behaviour skills (men) Kalichman (2005) Information, motivation and behaviour skills (women) Not stated 10, Information only delivered by counsellors in didactic style Information only delivered by counsellors in didactic style Bolu (2004) Enhanced counselling Didactic messages - informational intervention designed to approximate treatment as usual Bolu (2004) Brief counselling Didactic messages - informational intervention designed to approximate treatment as usual Source: NERA Analysis 18, , , , NERA Economic Consulting 30

36 Table 2.15 Threshold Analysis for Proportion in With STIs to Achieve 20,000 and 30,000 per QALY Counselling to Reduce STIs Study Control Cost per QALY Base case Control Base Case Base case Proportion in Group to Achieve 20,000 per QALY Proportion in Group to Achieve 30,000 per QALY Kamb (1998) Enhanced counselling Kamb (1998) Brief counselling Didactic messages - informational intervention designed to approximate treatment as usual Maher (2003) Intensive counselling Didactic messages - informational intervention designed to approximate treatment as usual Boyer (1997) Kalichman (2005) Kalichman (2005) Kalichman (2005) Behavioural skills counselling Information and behaviour skills (women) Information, motivation and behaviour skills (men) Information, motivation and Not stated 51, , , Not stated 96, Not stated 10, Information only delivered by counsellors in didactic style Information only delivered by counsellors in didactic 18, , NERA Economic Consulting 31

37 Study Control Cost per QALY Bolu (2004) behaviour skills (women) Enhanced counselling style Didactic messages - informational intervention designed to approximate treatment as usual Bolu (2004) Brief counselling Didactic messages - informational intervention designed to approximate treatment as usual Source: NERA Analysis Base case Control Base Case Base case Proportion in Group to Achieve 20,000 per QALY Proportion in Group to Achieve 30,000 per QALY 39, , NERA Economic Consulting 32

38 We also tested the sensitivity of results to the value of the QALY decrement as with accelerated partner therapy. The following figures illustrate our results. Figure 2.5 Sensitivity to QALY Decrement, Cost per QALY, QALY Decrement 0.01 to 1 Counselling to Reduce STIs 1,200,000 1,000, , , , , QALY Decrement Kamb (1998) EC Kamb (1998) BC Maher (2003) IC Boyer (1997) BSC Kalichman (2005) IBS W Kalichman (2005) IMB M Kalichman (2005) IMBS W Bolu (2004) EC Bolu (2004) BC James (1998) TSS Cost per QALY Source: NERA. NERA Economic Consulting 33

39 Figure 2.6 Sensitivity to QALY Decrement, Up to 30,000 per QALY, QALY Decrement 0.01 to 1 Counselling to Reduce STIs 30,000 25,000 20,000 15,000 10,000 5, QALY Decrement Kamb (1998) EC Kamb (1998) BC Maher (2003) IC Boyer (1997) BSC Kalichman (2005) IBS W Kalichman (2005) IMB M Kalichman (2005) IMBS W Bolu (2004) EC Bolu (2004) BC James (1998) TSS Cost per QALY Source: NERA. NERA Economic Consulting 34

40 Figure 2.7 Sensitivity to QALY Decrement, Up to 20,000 per QALY, QALY Decrement 0.01 to 1 Counselling to Reduce STIs 20,000 18,000 QALY Decrement 16,000 14,000 12,000 10,000 8,000 6,000 4,000 2,000 - Kamb (1998) EC Kamb (1998) BC Maher (2003) IC Boyer (1997) BSC Kalichman (2005) IBS W Kalichman (2005) IMB M Kalichman (2005) IMBS W Bolu (2004) EC Bolu (2004) BC James (1998) TSS Cost per QALY Source: NERA. We also considered how well rates seen in the studies matched rates seen in the English population and for selected groups of the population. This is essentially to test whether results would change if we apply the effect sizes to different groups who may be at particular high risk for STIs. Whilst the proportion effect of the intervention applied is the same, the baseline (i.e. the absolute numbers) change and thus impact on the cost per QALY. We use HPA data to provide rates per 1,000 for new diagnoses of Chlamydia and Gonorrhoea for the general English population and for year olds in the English population (the age group with the highest incidence). We note that the HPA does not calculate population rates for men who have sex with men or for Black and Minority Ethnic Groups. NERA Economic Consulting 35