EVerT: cryotherapy versus salicylic acid for the treatment of verrucae - a randomised controlled trial

Inclusion criteria

Potential participants were eligible for inclusion in the trial if they met the following criteria:

• They had a verruca which, in the opinion of the health-care professional, was suitable for treatment with both salicylic acid and cryotherapy.

• They were aged 12 years and over.

The study was funded via the NIHR HTA’s medicines for children call. Consequently, the initial inclusion criteria focused on children and young people between the ages of 12 and 24 years, inclusive. However, because of poor recruitment the upper age restriction was lifted.

Exclusion criteria

Potential participants were excluded if they met one or more of the following criteria:

• They were currently in a trial evaluating other treatments for their verruca.

• They had impaired healing, for example owing to diabetes, peripheral vascular disease or any other condition.

• They were immunosuppressed, for example had agammaglobulinaemia or were taking immunosuppressant drugs such as oral corticosteroids.

• They had neuropathy.

• They were currently on renal dialysis.

• They had cold intolerance, for example Raynaud syndrome or cold urticaria.

• They had any of the following conditions: blood dyscrasias of unknown origin, cryoglobulinaemia, cryofibrinogenaemia or collagen or autoimmune disease.

• They were unable to give informed consent.

Type and number of verruca(e)

The number and type of verruca(e) (mosaic or non-mosaic) were collected on the podiatrist treatment assessment form in order to examine whether or not mosaic verrucae respond less well to treatment than simple verrucae.

Duration and previous treatment of current verruca(e)

The duration of the current verruca(e) and type of any previous treatment received were recorded on the participant baseline questionnaire.

Reason for seeking treatment

The reasons for seeking treatment for the verrucae were recorded on the participant baseline questionnaire.

Level of pain

Participants were asked to rate how painful their current verruca was at baseline on a five-point Likert scale of 0–4, where 0 was not at all painful and 4 was extremely painful.

Number of previous verrucae and age at which they occurred

The number of previous verrucae and age at which they occurred were recorded on the participant baseline questionnaire.

Patient’s treatment preference

The patient’s treatment preference was recorded on the podiatrist treatment assessment form to allow us to explore the influence of the patient’s treatment preference on treatment outcomes.

Date of birth

Date of birth was recorded on the participant baseline questionnaire, allowing age at recruitment to be calculated and to allow us to explore the influence of the participant’s age on treatment outcomes.

Gender

The gender of participants was recorded on the participant baseline questionnaire.

Cryotherapy using liquid nitrogen delivered by the health-care professional

Patients randomised to cryotherapy using liquid nitrogen received up to a maximum of four treatments 14–21 days apart. Treatment was delivered by the health-care professional according to the usual practice of each trial site. Most of the health-care professionals delivering the cryotherapy had several years’ experience in delivering cryotherapy using liquid nitrogen. If a patient presented with more than one verruca, the health-care professional was instructed to treat the verrucae as they would in normal practice.

Prior to treatment, if it was the site’s normal practice, the callus surrounding the verruca(e) was debrided (e.g. with a scalpel or file) with any haemorrhages stopped by digital pressure only. The tissue surrounding the verruca was either masked (e.g. with petroleum jelly) or left unmasked, as per usual practice. Liquid nitrogen was applied using a spray (method of choice if available) or probe until the health-care professional was satisfied that the tissue had been frozen adequately. On the advice from the Trial Steering Committee (TSC), clinicians were advised that the first treatment should be a gentle freeze (approximately 10 seconds’ duration) in order to ensure that the patient could tolerate the treatment. Silver nitrate was not applied to the verruca. If necessary, the health-care professional could pad the area surrounding the verruca after treatment, for example with 7 mm of felt-cavity padding. Patients were given a cryotherapy patient’s advice sheet (see Appendix 3). Patients were also advised to keep the area dry for 24 hours and that the area may blister and be uncomfortable. If required, patients were recommended to use painkillers, as they would for a headache, if the area was very painful.

Daily self-treatment by the patient with 50% salicylic acid

Patients randomised to self-treatment with 50% salicylic acid were instructed how to use the salicylic acid by the health-care professional and were provided with a salicylic acid patient’s advice sheet (see Appendix 3) at the first trial appointment. Thereafter, the salicylic acid was applied once daily by the patient (or parent/guardian if appropriate) for a maximum of 8 weeks as per the manufacturer’s instructions as follows:

• The self-adhesive ring should be fixed with the hole over the verruca.

• Squeeze a little Verrugon ointment into the hole and directly onto the verruca.

• Remove backing paper from plaster.

• Cover ring completely with plaster. Seal into position.

• Repeat treatment daily after gently pumicing or filing off the dead part of the verruca.

All patients were given a follow-up appointment at 2 weeks as a safety check. Further supplies of felt pads, plasters and salicylic acid were provided to the patient when required. Patients were asked to return all of the tubes of salicylic acid they had received during the trial to the treating health-care professional at their 12-week appointment. The health-care professional weighed the tube(s) to determine how much salicylic acid had been used over the 8-week period.

Self-reported time to clearance of verrucae

Participants were asked to report if their verruca(e) had cleared on their week-3, week-12 and 6-month questionnaires (see Appendix 4) and, if it had cleared, on what date it cleared. In addition to this, participants were asked to return their ‘verruca gone form’ if their verrucae cleared at any other time points. If there was any discrepancy between the dates reported by the participant then the longest date to clearance was used.

Clearance of verrucae at 6 months

Clearance of verrucae at 6 months was recorded on the participant’s 6-month questionnaire. If the participant had verrucae at 6 months then the position of the verrucae (either in the original or in a new position) was recorded.

Number of verrucae remaining at the 12-week appointment

The number of verrucae remaining at 12 weeks was recorded on the podiatrist outcome assessment form to summarise the effects of the two regimens.

Recurrence of verrucae at 6 months

Participants were asked whether or not they had a verruca at 6 months on the participant’s 6-month questionnaire. If a verruca was present they were asked to record whether or not it was in the original or in a different place.

Patient satisfaction with treatment

Patient satisfaction with treatment (on a five-point scale, from ‘very unhappy’ to ‘very happy’) was reported on the participant week-1, week-3 and week-12 questionnaires.

Pain associated with first treatment

Pain associated with the first treatment (on a scale of 0–10, where 0 is no pain and 10 is the worst pain imaginable) was recorded on the patient pain questionnaire (see Appendix 4). This questionnaire was designed for participants to complete after their first treatment and return to the YTU using a reply-paid envelope.

Pain associated with verrucae and use of painkillers

Participants were asked to rate how painful their verrucae were on a five-point Likert scale of 0–4, where 0 was not at all painful and 4 was extremely painful. They were also asked to record if they needed to take a painkiller because of their verruca treatment during the first 3 weeks following entry into the study and, if yes, the number of days they took painkillers. Data were collected on the week-1 and week-3 questionnaires.

Treatment details

The number of appointments attended by each participant, excluding the week-12 outcome assessment appointment, were recorded by the health-care professional on the podiatrist treatment assessment form. Details of the cryotherapy delivered at each appointment were recorded by the health-care professional on the same form, including the number of freezes performed, the duration of the first freeze on that visit, whether or not the health-care professional considered that sufficient freezing took place and whether or not the patient asked for the freeze(s) to be stopped, and, if so, why. As a means of assessing adherence, the weight of salicylic acid ointment used over the treatment period was recorded by the health-care professional on the podiatrist treatment assessment form by weighing the tubes of salicylic acid at the start and end of treatment. In addition, the number of times salicylic acid was applied within the past 7 days was reported on the participants’ week-1 and week-3 questionnaires.

Adverse events

An adverse event was defined as ‘any untoward medical occurrence in a subject to whom a medicinal product has been administered, including occurrences which are not necessarily caused by or related to that product’.

Health-care professionals were asked to report any adverse events occurring in participants in both groups to the trial office using either the ‘serious adverse event form’ or the ‘non-serious adverse event form’ (see Appendix 4). The reporting health-care professional was asked to indicate whether or not, in his or her opinion, the event was related to the treatment. Serious adverse events were defined as an event that resulted in death, was life-threatening, required hospitalisation or prolongation of existing hospitalisation, resulted in a persistent or significant disability or incapacity, or resulted in a congenital anomaly or birth defect. When appropriate an assessment of intensity and expectedness was also undertaken.

A list of possible treatment-related adverse events was established, a priori, based on reports in the literature. These were pain, blistering, irritation to the skin, infection, burning sensation, bleeding, scarring and allergic contact reaction.

Health-care professionals were asked to report any serious adverse events within 24 hours of becoming aware of the event and provide a follow-up report if necessary.

Reasons for stopping treatment and any new treatments

Whether or not the participant found it necessary to stop the treatment to which they had been allocated and, if so, the reasons for this were recorded on the participant’s week-12 questionnaires. Whether or not they started another treatment, and, if so, what was the new treatment, was also recorded on the week-12 questionnaire.

Trial completion

The flow of participants through the trial is presented in a CONSORT diagram. The numbers of participants withdrawing from treatment and/or the trial were summarised together with the reasons where available.

Baseline data

All baseline data were summarised by treatment group and described descriptively. No formal statistical comparisons were undertaken. Continuous measures were reported as means and standard deviations (SDs), whereas categorical data were reported as counts and percentages.

Primary analysis

The primary outcome was complete clearance of all verrucae at 12 weeks. This was a dichotomous outcome (presence or absence of verruca). We compared the proportions of participants with complete clearance of all verrucae using a chi-squared test.

The Cohen’s kappa measure of inter-rater agreement was used to assess the agreement between the two assessors of the blinded photographs whether or not the verrucae had cleared.

Secondary analysis

Aim of the economic analysis

Economic evaluation of health interventions is a tool used to assist decision-makers in prioritising and allocating resources in the health-care sector, by assessing the value for money (cost-effectiveness) of alternative interventions.

The aim of the economic analysis was to assess the relative costs and effectiveness of cryotherapy and salicylic acid for the treatment of verrucae. Data on both costs and effectiveness of the two comparators were synthesised to assess the additional cost required for an additional unit of outcome. For this analysis, a cost-effectiveness approach was taken, where the outcome was defined as complete clearance of verrucae at 12 weeks.

The analysis was conducted on an ‘intention-to-treat’ basis. Hence, the analysis compared the treatment groups based on their original random allocation, regardless of protocol deviations and participants’ compliance or withdrawal. The NHS perspective was taken for the analysis where only costs directly linked to the NHS budget (GP or nurse visits, podiatrist time and cost of equipment and medications) were included.

Data

Methods for calculation of costs

Data analysis

The analysis of data was mainly dictated by the level of missing data for the primary outcome. The base-case analysis was conducted as a ‘complete case analysis’, where only patients with available primary outcome data were included. Where resource use data were missing, mean values were imputed based on the response group of the patients.

An additional analysis was conducted by including all the patients and performing multiple imputations on both the primary outcome and the missing total costs.

For both analyses, the mean differences in costs and effects and the 95% CIs around those were calculated by using bias-corrected and -accelerated (BCA) bootstrap methods. For the mean difference in costs, a linear regression was used, whereas logistic regression was used for the difference in primary outcome, given the binary nature of the data.

All the analyses were conducted using Stata statistic and data analysis software, version 10.1.

Determination of primary outcome

Table 9 shows the data comparing the outcomes from two independent assessors for photographs from 190 patients. Of these, 106 patients were deemed by both assessors to have verrucae, although both agreed that five patients’ verrucae had all cleared. The assessors disagreed in 51 cases: Assessor 1 classified that two patients had no verrucae, whereas Assessor 2 classified these patients as having verrucae. Similarly, Assessor 2 classified that one patient had no verrucae, whereas Assessor 1 classified them as still present. There were five cases in which Assessor 1 classified the verrucae as cleared, but Assessor 2 was unable to assess whether or not the verrucae had cleared. In the remaining 43 cases, the disagreement was between ‘not cleared’ and ‘unable to assess’ classifications. To quantify the strength of this association the kappa measure of agreement was estimated as 0.45 [standard error (SE) 0.05, 95% CI 0.35 to 0.55]. This indicates a moderate level of agreement.

Complete clearance of verrucae at 12 weeks adjusted analysis

The primary analysis was repeated but controlled for age, whether or not the verrucae had been previously treated (yes/no) and the type of verrucae (mosaic/non-mosaic). The results from the logistic regression highlighted that there was no evidence of a difference between the salicylic acid and the cryotherapy groups (OR 0.96, 95% CI 0.44 to 2.11; p = 0.92).

Age was categorised into three groups (< 18 years, > 18 but < 25 years, and over 25 years). There was a non-significant effect of age (< 18 years vs > 25 years, OR 0.66, 95% CI 0.22 to 1.98; and > 18 years but < 25 years vs > 25 years, OR 0.80, 95% CI 0.35 to 1.82).

After adjusting for clustering of healing rates within a centre there was still no evidence of a difference between the salicylic acid and the cryotherapy groups (OR 1.04, 95% CI 0.43 to 2.50; p = 0.92). The resultant intraclass correlation was almost zero (2.74 × 10^–10; p = 1.00).

Self-reported time to clearance of verrucae

We compared the time to clearance of the verrucae between the two groups, adjusting for the same covariates as above (age, previous treatment and type of verrucae). There was no evidence of a difference in the time to clearance between the two groups when compared in the Cox proportional hazards model [hazard ratio (HR) 0.80, 95% CI 0.51 to 1.25; p = 0.33].

Clearance of verrucae at 6 months

We received data on presence/absence of verrucae at 6 months from 193 participants. Overall, 62 of the 193 (32.1%) had complete clearance of all verrucae at 6 months: 29 of the 95 (30.5%) patients in the salicylic acid group and 33 out of the 98 (33.7%) patients in the cryotherapy group. There was no evidence of a difference between the salicylic acid and the cryotherapy groups (30.5% vs 33.7%, difference = –3.1%, 95% CI –10.0% to 16.3%; p = 0.64). The findings from the adjusted analysis were similar to the unadjusted analysis (OR 1.17, 95% CI 0.62 to 2.21; p = 0.62).

Number of verrucae remaining at 12 weeks

The median number of verrucae at 12 weeks in the salicylic acid group was 2 (minimum to maximum = 0–20) and in the cryotherapy group was 1 (minimum to maximum = 0–40). There was no evidence of a difference in the number of verrucae at 12 weeks between the two groups [incidence rate ratio (IRR) 1.08, 95% CI 0.8 to 1.43; p = 0.62].

Patient’s treatment preference

Twenty-eight (11.7%) and 86 (35.8%) participants expressed a preference at baseline for salicylic acid and cryotherapy, respectively, whereas 104 (43.3%) did not have a preference and 22 people did not respond to this question. When we extended the primary analysis to include an interaction term between randomised treatment and preferred treatment we found no evidence to suggest that patients’ preferences at baseline influenced the outcome.

Missing data

We investigated the sensitivity of the results to missing data with multiple imputation analysis. There was little difference in the estimates obtained from the complete case analysis and the multiple imputation analysis. The summary of the sensitivity of results to missing data is presented in Table 10.

Patients’ willingness to have the same treatment allocation

There was an association between willingness to have the same allocation and treatment randomised {chi-squared test statistic 17.90 [2 degrees of freedom (df)]; p = 0.0001}. More patients were willing to have cryotherapy again and fewer patients were willing to have salicylic acid again than expected under independent association.

Recurrence of verrucae at 6 months

Thirty-two patients had clearance of verrucae at 12 weeks. At 6 months, 22 of these 32 patients had reported their verrucae as gone, six had missing data and four (two patients in each group) reported that their verrucae had returned in its original place.

Patient satisfaction with treatment

Table 11 summarises patient satisfaction with treatment, reported on a five-point scale (from ‘very unhappy’ to ‘very happy’) on the participant week-1, week-3 and week-12 questionnaires.

At week 1, the majority of participants in both groups were happy with their treatment, with 68 individuals (67%) and 69 individuals (65%) in the cryotherapy and salicylic acid treatment groups, respectively, answering that they were either ‘happy’ or ‘very happy’. Only a small proportion of individuals (7% in the cryotherapy group and 6% in the salicylic acid group) were unhappy (answered ‘unhappy’ or ‘very unhappy’) with their treatment. At week 3, participants in both groups reported a similar level of satisfaction with their treatment to week 1. The majority (73% in the cryotherapy group and 61% in the salicylic acid group) reported that they were happy, and only 10% and 12% in the cryotherapy and salicylic acid treatment groups, respectively, reported that they were unhappy. At week 12, once again the majority (62%) of participants in the cryotherapy group reported that they were happy with their treatment and only 13% reported that they were unhappy. However, in the salicylic acid group individuals were less happy with their treatment than they were at previous time points and compared with the cryotherapy group at the week-12 time point. Forty individuals (41%) were happy, whereas 31 individuals (32%) were unhappy.

Whether or not the participants would be willing to receive the same treatment again is summarised in Table 12.

In total, 146 (77%) participants indicated at 12 weeks whether they would or would not have the same treatment again. The majority (n = 65, 71%) of cryotherapy patients reported that they would be willing to receive the same treatment again, whereas only 42 (43%) of salicylic acid patients were willing to repeat their treatment.

Pain associated with first treatment

Participants were asked to record the level of pain associated with their first treatment. This was reported on a 0–10 pain scale, where 0 represents no pain and 10 is the worst pain imaginable. The mean pain intensity associated with the first cryotherapy treatment was 3.05 (with a minimum score of 0 and a maximum score of 8), whereas the mean pain intensity associated with the first salicylic acid treatment was lower at 0.75 (with a minimum score of 0 and a maximum score of 7).

Pain associated with verrucae and use of painkillers

Pain associated with participants’ verrucae is summarised in Table 13. At weeks 1 and 3, the majority of participants in both treatment groups reported that their verrucae were not painful or a little painful. A minority reported a lot of pain (answering ‘quite a lot of pain’ or ‘extremely painful’).

A minority of participants found it necessary to take painkillers during the first 3 weeks of the study (n = 9), with more individuals taking painkillers in the cryotherapy group (n = 8) than in the salicylic acid group (n = 1). Those individuals who had used painkillers took them for between 1 and 4 days.

Treatment details

Table 14 summarises the cryotherapy treatment details reported by the treating health-care professional. Out of the 117 patients randomised to cryotherapy, treatment details were returned on the podiatrist treatment assessment form for 109 (93.2%) individuals and are summarised here. The mean number of visits to the clinic or GP practice for cryotherapy treatment was 3.6, with a minimum of one and a maximum of five visits. The mean duration between visits for treatment was 18.3 days, with a minimum of 9.7 days and a maximum of 52.5 days. At each treatment visit, participants received a mean of 1.6 applications of liquid nitrogen, with each application lasting a mean of 10.9 seconds. In the vast majority of cases (94.2%), the health-care professional considered that a sufficient freeze had been achieved and for only 9% of the freezes did the patient request that the freeze was stopped. The main reason for stopping the freeze was that it was painful.

Table 15 summarises the data collected on adherence for the salicylic acid treatment group. The majority (76%) of individuals received one tube of salicylic acid during the trial, and a mean of 2.8 g (SD 2.2 g) of ointment from each tube was used during the treatment period. Self-reported adherence was reasonably high, with participants applying salicylic acid on a mean of 6.3 days and 5.4 days out of 7 days at weeks 1 and 3, respectively.

Adverse events

In total, 19 participants reported 28 adverse events. Of these 28 events, one was classed as serious and unrelated to the treatment (salicylic acid). Of the remaining 27 events, 13 were in the salicylic acid group and 14 were in the cryotherapy group. The relationship between the non-serious adverse events and treatment group is reported in Table 16. There were two treatment-related non-serious adverse events, both of which were in the cryotherapy group. Both patients developed a blister that was larger in size than expected in routine practice.

Reasons for stopping treatment and any new treatments

Table 17 summarises the number of participants who found it necessary to stop their allocated treatment.

There was a low incidence of participants stopping their original treatment. Twenty-one participants (11.5%) reported stopping their original treatment. Of these, 16 participants were in the salicylic acid group and five in the cryotherapy group. The reasons for stopping treatment are summarised in Table 18.

Of the participants who reported stopping their original treatment, three (15%) reported starting another treatment. The cryotherapy patient started salicylic acid treatment and one of the salicylic acid patients continued their treatment with salicylic acid after a temporary stop. The other salicylic acid patient did not state which treatment they started.

Scenario 1: complete case analysis based on the primary outcome data

For the first scenario, only the patients who had primary outcome data were considered. Mean values were imputed for the missing resource usage items (i.e. treatments visits, additional visits to the GP or nurse, number of cryotherapy treatments, number of tubes of Verrugon). For the visits, the mean imputation was performed based on the outcome group (i.e. verrucae gone or not gone) and the treatment allocation. For the cryotherapy treatments and the number of Verrugon tubes, the means were imputed based on the outcome group only.

The total costs were calculated by summing up the cost of treatment visits, additional GP or nurse visits and the medication costs, i.e. the cost of cryotherapy equipment and liquid nitrogen per patient treatment for the cryotherapy group and the cost of Verrugon, pads and plasters for the salicylic acid group. Table 21 presents the costs by items of resource usage. The majority of costs for both groups was owing to the cost of treatment visits, with the average cost per patient being larger in the cryotherapy group than in the salicylic acid group (£88.69 vs £39.59). The second largest cost for the cryotherapy group was the cost of treatment, which included the cost of equipment and liquid nitrogen. The average cost of the cryotherapy treatment per patient was £60.05.

To avoid any distributional assumptions on the cost and outcome data, the BCA 95% CIs around the mean difference in costs and outcomes were calculated by the bootstrapping method. The mean differences in costs and the proportion of patients with cleared verrucae were calculated based on linear regression for the former and logistic regression for the latter. Two types of analyses were conducted: first, based on unadjusted costs and outcomes and, second, by adjusting them based on the age of the participants, whether or not they had received previous treatment and the type of verrucae.

Cost-effectiveness and uncertainty

As demonstrated in Tables 23 and 24, cryotherapy is more costly and non-significantly less effective. The bootstrapped pairs of difference in costs and outcomes for both adjusted and unadjusted results are presented on a cost-effectiveness plane (CE plane) (see Figure 3) to visually demonstrate the above conclusions. As evident from the CE plane, almost 50% of the bootstrapped replicates falls either side of the line that goes through the zero difference in outcomes point (x-axis). This is indicative of high uncertainty around the difference in effectiveness of the two treatments. In contrast, all of the cost replicates are above the zero line of the y-axis, i.e. no difference in costs. Figure 3 presents the CE plane for both unadjusted and adjusted results.

FIGURE 3.

Cost-effectiveness plane for unadjusted and adjusted costs and outcomes.

Figure 4 presents the CEACs. This demonstrates the probability of the cryotherapy being cost-effective given a specific willingness-to-pay value per ‘cured’ patient. The adjusted and unadjusted data give the same results. In both cases, the probability that cryotherapy is cost-effective is around 40% at a threshold value of £15,000 per cured patient.

FIGURE 4.

Cost-effectiveness acceptability curves (adjusted and unadjusted data).

Sensitivity analysis based on the data analysis of scenario 1 (complete case for primary outcome data)

The majority of costs for the cryotherapy group are owing to treatment visits (i.e. health-care professional’s time) and the cost of the treatment itself, i.e. the cost of the equipment and liquid nitrogen. A sensitivity analysis was carried out by adopting an extreme approach whereby the administration of the treatment was assumed to be carried out by a nurse (rather than a GP) in those study sites that were set up in GP practices and by excluding completely the cost of cryotherapy equipment and liquid nitrogen. In effect, this analysis would result in comparing both treatments based on the treatment visits only rather than including the cost of medication as well. Table 25 presents the results of the sensitivity analysis. Cryotherapy is again more costly than salicylic acid treatment. This is because of the greater number of treatment visits that the patients made, even though the cost of the health-care professional who administered the cryotherapy was lower (nurse vs GP).

Figures 5 and 6 present the CE planes and CEACs for both unadjusted and adjusted results of the sensitivity analysis. Cryotherapy remains more costly and all of the bootstrapped replicates of difference in costs are above the zero line, although outcome results do not change. The smaller difference in costs between the two treatments (compared with the base-case analysis) results in cryotherapy having an approximately 40% probability of being cost-effective at a lower (than the base-case analysis) threshold.

FIGURE 5.

Cost-effectiveness planes for unadjusted and adjusted costs and outcomes.

FIGURE 6.

Cost-effectiveness acceptability curve for the sensitivity analysis.

Scenario 2: multiple imputation on the primary outcome data and on the missing total costs

Data were imputed by using multiple imputation methods for the 11 patients who had missing primary outcome data. The multiple imputations were performed by using age, previous treatment and type of verrucae as covariates. Data were imputed also for the missing total costs of these 11 patients.

The mean differences in costs and outcomes after multiple imputation are presented in Table 26. The CE plane and CEAC are presented in Figures 7 and 8. The results of the multiple imputation do not alter the overall conclusion of the study that cryotherapy is more costly than salicylic acid and that there is no evidence of it being more effective.

FIGURE 7.

Cost-effectiveness plane (multiply imputed data).

FIGURE 8.

Cost-effectiveness acceptability curve (multiply imputed data).

Prioritisation Group

1. Director, NIHR HTA programme, Professor of Clinical Pharmacology, University of Liverpool

2. Professor Imti Choonara, Professor in Child Health, Academic Division of Child Health, University of Nottingham

   Chair – Pharmaceuticals Panel

3. Dr Bob Coates, Consultant Advisor – Disease Prevention Panel

4. Dr Andrew Cook, Consultant Advisor – Intervention Procedures Panel

5. Dr Peter Davidson, Director of NETSCC, Health Technology Assessment

6. Dr Nick Hicks, Consultant Adviser – Diagnostic Technologies and Screening Panel, Consultant Advisor–Psychological and Community Therapies Panel

7. Ms Susan Hird, Consultant Advisor, External Devices and Physical Therapies Panel

8. Professor Sallie Lamb, Director, Warwick Clinical Trials Unit, Warwick Medical School, University of Warwick

   Chair – HTA Clinical Evaluation and Trials Board

9. Professor Jonathan Michaels, Professor of Vascular Surgery, Sheffield Vascular Institute, University of Sheffield

   Chair – Interventional Procedures Panel

10. Professor Ruairidh Milne, Director – External Relations

11. Dr John Pounsford, Consultant Physician, Directorate of Medical Services, North Bristol NHS Trust

    Chair – External Devices and Physical Therapies Panel

12. Dr Vaughan Thomas, Consultant Advisor – Pharmaceuticals Panel, Clinical

    Lead – Clinical Evaluation Trials Prioritisation Group

13. Professor Margaret Thorogood, Professor of Epidemiology, Health Sciences Research Institute, University of Warwick

    Chair – Disease Prevention Panel

14. Professor Lindsay Turnbull, Professor of Radiology, Centre for the MR Investigations, University of Hull

    Chair – Diagnostic Technologies and Screening Panel

15. Professor Scott Weich, Professor of Psychiatry, Health Sciences Research Institute, University of Warwick

    Chair – Psychological and Community Therapies Panel

16. Professor Hywel Williams, Director of Nottingham Clinical Trials Unit, Centre of Evidence-Based Dermatology, University of Nottingham

    Chair – HTA Commissioning Board

    Deputy HTA Programme Director

HTA Commissioning Board

1. Professor of Dermato-Epidemiology, Centre of Evidence-Based Dermatology, University of Nottingham

2. Department of Public Health and Epidemiology, University of Birmingham

3. Professor of Clinical Pharmacology, Director, NIHR HTA programme, University of Liverpool

1. Professor Ann Ashburn, Professor of Rehabilitation and Head of Research, Southampton General Hospital

2. Professor Peter Brocklehurst, Professor of Women’s Health, Institute for Women’s Health, University College London

3. Professor Jenny Donovan, Professor of Social Medicine, University of Bristol

4. Professor Jonathan Green, Professor and Acting Head of Department, Child and Adolescent Psychiatry, University of Manchester Medical School

5. Professor John W Gregory, Professor in Paediatric Endocrinology, Department of Child Health, Wales School of Medicine, Cardiff University

6. Professor Steve Halligan, Professor of Gastrointestinal Radiology, University College Hospital, London

7. Professor Freddie Hamdy, Professor of Urology, Head of Nuffield Department of Surgery, University of Oxford

8. Professor Allan House, Professor of Liaison Psychiatry, University of Leeds

9. Dr Martin J Landray, Reader in Epidemiology, Honorary Consultant Physician, Clinical Trial Service Unit, University of Oxford

10. Professor Stephen Morris, Professor of Health Economics, University College London, Research Department of Epidemiology and Public Health, University College London

11. Professor Irwin Nazareth, Professor of Primary Care and Head of Department, Department of Primary Care and Population Sciences, University College London

12. Professor E Andrea Nelson, Professor of Wound Healing and Director of Research, School of Healthcare, University of Leeds

13. Professor John David Norrie, Chair in Clinical Trials and Biostatistics, Robertson Centre for Biostatistics, University of Glasgow

14. Dr Rafael Perera, Lecturer in Medical Statisitics, Department of Primary Health Care, University of Oxford

15. Professor Barney Reeves, Professorial Research Fellow in Health Services Research, Department of Clinical Science, University of Bristol

16. Professor Martin Underwood, Professor of Primary Care Research, Warwick Medical School, University of Warwick

17. Professor Marion Walker, Professor in Stroke Rehabilitation, Associate Director UK Stroke Research Network, University of Nottingham

18. Dr Duncan Young, Senior Clinical Lecturer and Consultant, Nuffield Department of Anaesthetics, University of Oxford

1. Dr Tom Foulks, Medical Research Council

2. Dr Kay Pattison, Senior NIHR Programme Manager, Department of Health

HTA Clinical Evaluation and Trials Board

1. Director, Warwick Clinical Trials Unit, Warwick Medical School, University of Warwick and Professor of Rehabilitation, Nuffield Department of Orthopaedic, Rheumatology and Musculoskeletal Sciences, University of Oxford

2. Professor of the Psychology of Health Care, Leeds Institute of Health Sciences, University of Leeds

3. Director, NIHR HTA programme, Professor of Clinical Pharmacology, University of Liverpool

1. Professor Keith Abrams, Professor of Medical Statistics, Department of Health Sciences, University of Leicester

2. Professor Martin Bland, Professor of Health Statistics, Department of Health Sciences, University of York

3. Professor Jane Blazeby, Professor of Surgery and Consultant Upper GI Surgeon, Department of Social Medicine, University of Bristol

4. Professor Julia M Brown, Director, Clinical Trials Research Unit, University of Leeds

5. Professor Alistair Burns, Professor of Old Age Psychiatry, Psychiatry Research Group, School of Community-Based Medicine, The University of Manchester & National Clinical Director for Dementia, Department of Health

6. Dr Jennifer Burr, Director, Centre for Healthcare Randomised trials (CHART), University of Aberdeen

7. Professor Linda Davies, Professor of Health Economics, Health Sciences Research Group, University of Manchester

8. Professor Simon Gilbody, Prof of Psych Medicine and Health Services Research, Department of Health Sciences, University of York

9. Professor Steven Goodacre, Professor and Consultant in Emergency Medicine, School of Health and Related Research, University of Sheffield

10. Professor Dyfrig Hughes, Professor of Pharmacoeconomics, Centre for Economics and Policy in Health, Institute of Medical and Social Care Research, Bangor University

11. Professor Paul Jones, Professor of Respiratory Medicine, Department of Cardiac and Vascular Science, St George‘s Hospital Medical School, University of London

12. Professor Khalid Khan, Professor of Women’s Health and Clinical Epidemiology, Barts and the London School of Medicine, Queen Mary, University of London

13. Professor Richard J McManus, Professor of Primary Care Cardiovascular Research, Primary Care Clinical Sciences Building, University of Birmingham

14. Professor Helen Rodgers, Professor of Stroke Care, Institute for Ageing and Health, Newcastle University

15. Professor Ken Stein, Professor of Public Health, Peninsula Technology Assessment Group, Peninsula College of Medicine and Dentistry, Universities of Exeter and Plymouth

16. Professor Jonathan Sterne, Professor of Medical Statistics and Epidemiology, Department of Social Medicine, University of Bristol

17. Mr Andy Vail, Senior Lecturer, Health Sciences Research Group, University of Manchester

18. Professor Clare Wilkinson, Professor of General Practice and Director of Research North Wales Clinical School, Department of Primary Care and Public Health, Cardiff University

19. Dr Ian B Wilkinson, Senior Lecturer and Honorary Consultant, Clinical Pharmacology Unit, Department of Medicine, University of Cambridge

1. Ms Kate Law, Director of Clinical Trials, Cancer Research UK

2. Dr Morven Roberts, Clinical Trials Manager, Health Services and Public Health Services Board, Medical Research Council

Diagnostic Technologies and Screening Panel

1. Scientific Director of the Centre for Magnetic Resonance Investigations and YCR Professor of Radiology, Hull Royal Infirmary

2. Professor Judith E Adams, Consultant Radiologist, Manchester Royal Infirmary, Central Manchester & Manchester Children’s University Hospitals NHS Trust, and Professor of Diagnostic Radiology, University of Manchester

3. Mr Angus S Arunkalaivanan, Honorary Senior Lecturer, University of Birmingham and Consultant Urogynaecologist and Obstetrician, City Hospital, Birmingham

4. Dr Diana Baralle, Consultant and Senior Lecturer in Clinical Genetics, University of Southampton

5. Dr Stephanie Dancer, Consultant Microbiologist, Hairmyres Hospital, East Kilbride

6. Dr Diane Eccles, Professor of Cancer Genetics, Wessex Clinical Genetics Service, Princess Anne Hospital

7. Dr Trevor Friedman, Consultant Liason Psychiatrist, Brandon Unit, Leicester General Hospital

8. Dr Ron Gray, Consultant, National Perinatal Epidemiology Unit, Institute of Health Sciences, University of Oxford

9. Professor Paul D Griffiths, Professor of Radiology, Academic Unit of Radiology, University of Sheffield

10. Mr Martin Hooper, Public contributor

11. Professor Anthony Robert Kendrick, Associate Dean for Clinical Research and Professor of Primary Medical Care, University of Southampton

12. Dr Nicola Lennard, Senior Medical Officer, MHRA

13. Dr Anne Mackie, Director of Programmes, UK National Screening Committee, London

14. Mr David Mathew, Public contributor

15. Dr Michael Millar, Consultant Senior Lecturer in Microbiology, Department of Pathology & Microbiology, Barts and The London NHS Trust, Royal London Hospital

16. Mrs Una Rennard, Public contributor

17. Dr Stuart Smellie, Consultant in Clinical Pathology, Bishop Auckland General Hospital

18. Ms Jane Smith, Consultant Ultrasound Practitioner, Leeds Teaching Hospital NHS Trust, Leeds

19. Dr Allison Streetly, Programme Director, NHS Sickle Cell and Thalassaemia Screening Programme, King’s College School of Medicine

20. Dr Matthew Thompson, Senior Clinical Scientist and GP, Department of Primary Health Care, University of Oxford

21. Dr Alan J Williams, Consultant Physician, General and Respiratory Medicine, The Royal Bournemouth Hospital

1. Dr Tim Elliott, Team Leader, Cancer Screening, Department of Health

2. Dr Joanna Jenkinson, Board Secretary, Neurosciences and Mental Health Board (NMHB), Medical Research Council

3. Professor Julietta Patrick, Director, NHS Cancer Screening Programme, Sheffield

4. Dr Kay Pattison, Senior NIHR Programme Manager, Department of Health

5. Professor Tom Walley, CBE, Director, NIHR HTA programme, Professor of Clinical Pharmacology, University of Liverpool

6. Dr Ursula Wells, Principal Research Officer, Policy Research Programme, Department of Health

Disease Prevention Panel

1. Professor of Epidemiology, University of Warwick Medical School, Coventry

2. Dr Robert Cook, Clinical Programmes Director, Bazian Ltd, London

3. Dr Colin Greaves, Senior Research Fellow, Peninsula Medical School (Primary Care)

4. Mr Michael Head, Public contributor

5. Professor Cathy Jackson, Professor of Primary Care Medicine, Bute Medical School, University of St Andrews

6. Dr Russell Jago, Senior Lecturer in Exercise, Nutrition and Health, Centre for Sport, Exercise and Health, University of Bristol

7. Dr Julie Mytton, Consultant in Child Public Health, NHS Bristol

8. Professor Irwin Nazareth, Professor of Primary Care and Director, Department of Primary Care and Population Sciences, University College London

9. Dr Richard Richards, Assistant Director of Public Health, Derbyshire County Primary Care Trust

10. Professor Ian Roberts, Professor of Epidemiology and Public Health, London School of Hygiene & Tropical Medicine

11. Dr Kenneth Robertson, Consultant Paediatrician, Royal Hospital for Sick Children, Glasgow

12. Dr Catherine Swann, Associate Director, Centre for Public Health Excellence, NICE

13. Mrs Jean Thurston, Public contributor

14. Professor David Weller, Head, School of Clinical Science and Community Health, University of Edinburgh

1. Ms Christine McGuire, Research & Development, Department of Health

2. Dr Kay Pattison, Senior NIHR Programme Manager, Department of Health

3. Professor Tom Walley, CBE, Director, NIHR HTA programme, Professor of Clinical Pharmacology, University of Liverpool

External Devices and Physical Therapies Panel

1. Consultant Physician North Bristol NHS Trust

2. Reader in Wound Healing and Director of Research, University of Leeds

3. Professor Bipin Bhakta, Charterhouse Professor in Rehabilitation Medicine, University of Leeds

4. Mrs Penny Calder, Public contributor

5. Dr Dawn Carnes, Senior Research Fellow, Barts and the London School of Medicine and Dentistry

6. Dr Emma Clark, Clinician Scientist Fellow & Cons. Rheumatologist, University of Bristol

7. Mrs Anthea De Barton-Watson, Public contributor

8. Professor Nadine Foster, Professor of Musculoskeletal Health in Primary Care Arthritis Research, Keele University

9. Dr Shaheen Hamdy, Clinical Senior Lecturer and Consultant Physician, University of Manchester

10. Professor Christine Norton, Professor of Clinical Nursing Innovation, Bucks New University and Imperial College Healthcare NHS Trust

11. Dr Lorraine Pinnigton, Associate Professor in Rehabilitation, University of Nottingham

12. Dr Kate Radford, Senior Lecturer (Research), University of Central Lancashire

13. Mr Jim Reece, Public contributor

14. Professor Maria Stokes, Professor of Neuromusculoskeletal Rehabilitation, University of Southampton

15. Dr Pippa Tyrrell, Senior Lecturer/Consultant, Salford Royal Foundation Hospitals’ Trust and University of Manchester

16. Dr Nefyn Williams, Clinical Senior Lecturer, Cardiff University

1. Dr Kay Pattison, Senior NIHR Programme Manager, Department of Health

2. Dr Morven Roberts, Clinical Trials Manager, Health Services and Public Health Services Board, Medical Research Council

3. Professor Tom Walley, CBE, Director, NIHR HTA programme, Professor of Clinical Pharmacology, University of Liverpool

4. Dr Ursula Wells, Principal Research Officer, Policy Research Programme, Department of Health

Interventional Procedures Panel

1. Professor of Vascular Surgery, University of Sheffield

2. Consultant Colorectal Surgeon, Bristol Royal Infirmary

3. Mrs Isabel Boyer, Public contributor

4. Mr Sankaran Chandra Sekharan, Consultant Surgeon, Breast Surgery, Colchester Hospital University NHS Foundation Trust

5. Professor Nicholas Clarke, Consultant Orthopaedic Surgeon, Southampton University Hospitals NHS Trust

6. Ms Leonie Cooke, Public contributor

7. Mr Seumas Eckford, Consultant in Obstetrics & Gynaecology, North Devon District Hospital

8. Professor Sam Eljamel, Consultant Neurosurgeon, Ninewells Hospital and Medical School, Dundee

9. Dr Adele Fielding, Senior Lecturer and Honorary Consultant in Haematology, University College London Medical School

10. Dr Matthew Hatton, Consultant in Clinical Oncology, Sheffield Teaching Hospital Foundation Trust

11. Dr John Holden, General Practitioner, Garswood Surgery, Wigan

12. Dr Fiona Lecky, Senior Lecturer/Honorary Consultant in Emergency Medicine, University of Manchester/Salford Royal Hospitals NHS Foundation Trust

13. Dr Nadim Malik, Consultant Cardiologist/Honorary Lecturer, University of Manchester

14. Mr Hisham Mehanna, Consultant & Honorary Associate Professor, University Hospitals Coventry & Warwickshire NHS Trust

15. Dr Jane Montgomery, Consultant in Anaesthetics and Critical Care, South Devon Healthcare NHS Foundation Trust

16. Professor Jon Moss, Consultant Interventional Radiologist, North Glasgow Hospitals University NHS Trust

17. Dr Simon Padley, Consultant Radiologist, Chelsea & Westminster Hospital

18. Dr Ashish Paul, Medical Director, Bedfordshire PCT

19. Dr Sarah Purdy, Consultant Senior Lecturer, University of Bristol

20. Dr Matthew Wilson, Consultant Anaesthetist, Sheffield Teaching Hospitals NHS Foundation Trust

21. Professor Yit Chiun Yang, Consultant Ophthalmologist, Royal Wolverhampton Hospitals NHS Trust

1. Dr Kay Pattison, Senior NIHR Programme Manager, Department of Health

2. Dr Morven Roberts, Clinical Trials Manager, Health Services and Public Health Services Board, Medical Research Council

3. Professor Tom Walley, CBE, Director, NIHR HTA programme, Professor of Clinical Pharmacology, University of Liverpool

4. Dr Ursula Wells, Principal Research Officer, Policy Research Programme, Department of Health

Pharmaceuticals Panel

1. Professor in Child Health, University of Nottingham

2. Senior Lecturer in Clinical Pharmacology, University of East Anglia

3. Dr Martin Ashton-Key, Medical Advisor, National Commissioning Group, NHS London

4. Dr Peter Elton, Director of Public Health, Bury Primary Care Trust

5. Dr Ben Goldacre, Research Fellow, Division of Psychological Medicine and Psychiatry, King’s College London

6. Dr James Gray, Consultant Microbiologist, Department of Microbiology, Birmingham Children’s Hospital NHS Foundation Trust

7. Dr Jurjees Hasan, Consultant in Medical Oncology, The Christie, Manchester

8. Dr Carl Heneghan, Deputy Director Centre for Evidence-Based Medicine and Clinical Lecturer, Department of Primary Health Care, University of Oxford

9. Dr Dyfrig Hughes, Reader in Pharmacoeconomics and Deputy Director, Centre for Economics and Policy in Health, IMSCaR, Bangor University

10. Dr Maria Kouimtzi, Pharmacy and Informatics Director, Global Clinical Solutions, Wiley-Blackwell

11. Professor Femi Oyebode, Consultant Psychiatrist and Head of Department, University of Birmingham

12. Dr Andrew Prentice, Senior Lecturer and Consultant Obstetrician and Gynaecologist, The Rosie Hospital, University of Cambridge

13. Ms Amanda Roberts, Public contributor

14. Dr Gillian Shepherd, Director, Health and Clinical Excellence, Merck Serono Ltd

15. Mrs Katrina Simister, Assistant Director New Medicines, National Prescribing Centre, Liverpool

16. Professor Donald Singer, Professor of Clinical Pharmacology and Therapeutics, Clinical Sciences Research Institute, CSB, University of Warwick Medical School

17. Mr David Symes, Public contributor

18. Dr Arnold Zermansky, General Practitioner, Senior Research Fellow, Pharmacy Practice and Medicines Management Group, Leeds University

1. Dr Kay Pattison, Senior NIHR Programme Manager, Department of Health

2. Mr Simon Reeve, Head of Clinical and Cost-Effectiveness, Medicines, Pharmacy and Industry Group, Department of Health

3. Dr Heike Weber, Programme Manager, Medical Research Council

4. Professor Tom Walley, CBE, Director, NIHR HTA programme, Professor of Clinical Pharmacology, University of Liverpool

5. Dr Ursula Wells, Principal Research Officer, Policy Research Programme, Department of Health

Psychological and Community Therapies Panel

1. Professor of Psychiatry, University of Warwick, Coventry

2. Consultant & University Lecturer in Psychiatry, University of Cambridge

3. Professor Jane Barlow, Professor of Public Health in the Early Years, Health Sciences Research Institute, Warwick Medical School

4. Dr Sabyasachi Bhaumik, Consultant Psychiatrist, Leicestershire Partnership NHS Trust

5. Mrs Val Carlill, Public contributor

6. Dr Steve Cunningham, Consultant Respiratory Paediatrician, Lothian Health Board

7. Dr Anne Hesketh, Senior Clinical Lecturer in Speech and Language Therapy, University of Manchester

8. Dr Peter Langdon, Senior Clinical Lecturer, School of Medicine, Health Policy and Practice, University of East Anglia

9. Dr Yann Lefeuvre, GP Partner, Burrage Road Surgery, London

10. Dr Jeremy J Murphy, Consultant Physician and Cardiologist, County Durham and Darlington Foundation Trust

11. Dr Richard Neal, Clinical Senior Lecturer in General Practice, Cardiff University

12. Mr John Needham, Public contributor

13. Ms Mary Nettle, Mental Health User Consultant

14. Professor John Potter, Professor of Ageing and Stroke Medicine, University of East Anglia

15. Dr Greta Rait, Senior Clinical Lecturer and General Practitioner, University College London

16. Dr Paul Ramchandani, Senior Research Fellow/Cons. Child Psychiatrist, University of Oxford

17. Dr Karen Roberts, Nurse/Consultant, Dunston Hill Hospital, Tyne and Wear

18. Dr Karim Saad, Consultant in Old Age Psychiatry, Coventry and Warwickshire Partnership Trust

19. Dr Lesley Stockton, Lecturer, School of Health Sciences, University of Liverpool

20. Dr Simon Wright, GP Partner, Walkden Medical Centre, Manchester

1. Dr Kay Pattison, Senior NIHR Programme Manager, Department of Health

2. Dr Morven Roberts, Clinical Trials Manager, Health Services and Public Health Services Board, Medical Research Council

3. Professor Tom Walley, CBE, Director, NIHR HTA programme, Professor of Clinical Pharmacology, University of Liverpool

4. Dr Ursula Wells, Principal Research Officer, Policy Research Programme, Department of Health

Expert Advisory Network

1. Professor Douglas Altman, Professor of Statistics in Medicine, Centre for Statistics in Medicine, University of Oxford

2. Professor John Bond, Professor of Social Gerontology & Health Services Research, University of Newcastle upon Tyne

3. Professor Andrew Bradbury, Professor of Vascular Surgery, Solihull Hospital, Birmingham

4. Mr Shaun Brogan, Chief Executive, Ridgeway Primary Care Group, Aylesbury

5. Mrs Stella Burnside OBE, Chief Executive, Regulation and Improvement Authority, Belfast

6. Ms Tracy Bury, Project Manager, World Confederation of Physical Therapy, London

7. Professor Iain T Cameron, Professor of Obstetrics and Gynaecology and Head of the School of Medicine, University of Southampton

8. Professor Bruce Campbell, Consultant Vascular & General Surgeon, Royal Devon & Exeter Hospital, Wonford

9. Dr Christine Clark, Medical Writer and Consultant Pharmacist, Rossendale

10. Professor Collette Clifford, Professor of Nursing and Head of Research, The Medical School, University of Birmingham

11. Professor Barry Cookson, Director, Laboratory of Hospital Infection, Public Health Laboratory Service, London

12. Dr Carl Counsell, Clinical Senior Lecturer in Neurology, University of Aberdeen

13. Professor Howard Cuckle, Professor of Reproductive Epidemiology, Department of Paediatrics, Obstetrics & Gynaecology, University of Leeds

14. Professor Carol Dezateux, Professor of Paediatric Epidemiology, Institute of Child Health, London

15. Mr John Dunning, Consultant Cardiothoracic Surgeon, Papworth Hospital NHS Trust, Cambridge

16. Mr Jonothan Earnshaw, Consultant Vascular Surgeon, Gloucestershire Royal Hospital, Gloucester

17. Professor Martin Eccles, Professor of Clinical Effectiveness, Centre for Health Services Research, University of Newcastle upon Tyne

18. Professor Pam Enderby, Dean of Faculty of Medicine, Institute of General Practice and Primary Care, University of Sheffield

19. Professor Gene Feder, Professor of Primary Care Research & Development, Centre for Health Sciences, Barts and The London School of Medicine and Dentistry

20. Mr Leonard R Fenwick, Chief Executive, Freeman Hospital, Newcastle upon Tyne

21. Mrs Gillian Fletcher, Antenatal Teacher and Tutor and President, National Childbirth Trust, Henfield

22. Professor Jayne Franklyn, Professor of Medicine, University of Birmingham

23. Mr Tam Fry, Honorary Chairman, Child Growth Foundation, London

24. Professor Fiona Gilbert, Consultant Radiologist and NCRN Member, University of Aberdeen

25. Professor Paul Gregg, Professor of Orthopaedic Surgical Science, South Tees Hospital NHS Trust

26. Bec Hanley, Co-director, TwoCan Associates, West Sussex

27. Dr Maryann L Hardy, Senior Lecturer, University of Bradford

28. Mrs Sharon Hart, Healthcare Management Consultant, Reading

29. Professor Robert E Hawkins, CRC Professor and Director of Medical Oncology, Christie CRC Research Centre, Christie Hospital NHS Trust, Manchester

30. Professor Richard Hobbs, Head of Department of Primary Care & General Practice, University of Birmingham

31. Professor Alan Horwich, Dean and Section Chairman, The Institute of Cancer Research, London

32. Professor Allen Hutchinson, Director of Public Health and Deputy Dean of ScHARR, University of Sheffield

33. Professor Peter Jones, Professor of Psychiatry, University of Cambridge, Cambridge

34. Professor Stan Kaye, Cancer Research UK Professor of Medical Oncology, Royal Marsden Hospital and Institute of Cancer Research, Surrey

35. Dr Duncan Keeley, General Practitioner (Dr Burch & Ptnrs), The Health Centre, Thame

36. Dr Donna Lamping, Research Degrees Programme Director and Reader in Psychology, Health Services Research Unit, London School of Hygiene and Tropical Medicine, London

37. Professor James Lindesay, Professor of Psychiatry for the Elderly, University of Leicester

38. Professor Julian Little, Professor of Human Genome Epidemiology, University of Ottawa

39. Professor Alistaire McGuire, Professor of Health Economics, London School of Economics

40. Professor Neill McIntosh, Edward Clark Professor of Child Life and Health, University of Edinburgh

41. Professor Rajan Madhok, Consultant in Public Health, South Manchester Primary Care Trust

42. Professor Sir Alexander Markham, Director, Molecular Medicine Unit, St James’s University Hospital, Leeds

43. Dr Peter Moore, Freelance Science Writer, Ashtead

44. Dr Andrew Mortimore, Public Health Director, Southampton City Primary Care Trust

45. Dr Sue Moss, Associate Director, Cancer Screening Evaluation Unit, Institute of Cancer Research, Sutton

46. Professor Miranda Mugford, Professor of Health Economics and Group Co-ordinator, University of East Anglia

47. Professor Jim Neilson, Head of School of Reproductive & Developmental Medicine and Professor of Obstetrics and Gynaecology, University of Liverpool

48. Mrs Julietta Patnick, Director, NHS Cancer Screening Programmes, Sheffield

49. Professor Robert Peveler, Professor of Liaison Psychiatry, Royal South Hants Hospital, Southampton

50. Professor Chris Price, Director of Clinical Research, Bayer Diagnostics Europe, Stoke Poges

51. Professor William Rosenberg, Professor of Hepatology and Consultant Physician, University of Southampton

52. Professor Peter Sandercock, Professor of Medical Neurology, Department of Clinical Neurosciences, University of Edinburgh

53. Dr Philip Shackley, Senior Lecturer in Health Economics, Sheffield Vascular Institute, University of Sheffield

54. Dr Eamonn Sheridan, Consultant in Clinical Genetics, St James’s University Hospital, Leeds

55. Dr Margaret Somerville, Director of Public Health Learning, Peninsula Medical School, University of Plymouth

56. Professor Sarah Stewart-Brown, Professor of Public Health, Division of Health in the Community, University of Warwick, Coventry

57. Dr Nick Summerton, GP Appraiser and Codirector, Research Network, Yorkshire Clinical Consultant, Primary Care and Public Health, University of Oxford

58. Professor Ala Szczepura, Professor of Health Service Research, Centre for Health Services Studies, University of Warwick, Coventry

59. Dr Ross Taylor, Senior Lecturer, University of Aberdeen

60. Dr Richard Tiner, Medical Director, Medical Department, Association of the British Pharmaceutical Industry

61. Mrs Joan Webster, Consumer Member, Southern Derbyshire Community Health Council

62. Professor Martin Whittle, Clinical Co-director, National Co-ordinating Centre for Women’s and Children’s Health, Lymington