Technology Assessments

We lead the health economics component of health technology assessments undertaken across the IAHS. These include NIHR funded and externally funded trials and cohort studies of new and existing interventions. The research is generally multidisciplinary and undertaken in collaboration with research groups in the University of Aberdeen and external centres of excellence.

Current Projects

BiCARB - Oral sodium bicarbonate for low grade acidosis in kidney patients

Does oral sodium bicarbonate therapy improve function and quality of life in older patients with chronic kidney disease and low-grade acidosis? A randomised controlled trial

A randomised controlled trial is being undertaken to test whether bicarbonate treatment makes older people with advanced kidney disease healthier. 380 patients will receive either bicarbonate or dummy (placebo) tablets three times a day for two years.

We test muscle strength and bulk, walking and balance ability, quality of life, kidney, bone and blood vessel function at intervals over the two-year period. We record blood pressure and side effects, record falls, admissions to hospital and contact with GPs, and also test the cost of treatment against the cost of not treating.

International Standard Randomised Controlled Trial Number Register number ISRCTN09486651

HERU researchers involved in this research project: Paul McNamee and Huey Chong.

External collaborators: M Witham (University of Dundee), A Avenell (HSRU, University of Aberdeen) and R Soiza (School of Medicine, Medical Sciences and Nutrition, University of Aberdeen).

BSRBR-AS - British Society for Rheumatology Biologics Register in Ankylosing Spondylitis

The British Society for Rheumatology Biologics Register – Ankylosing Spondylitis (BSRBR-AS) was established to monitor the safety of biologic treatments for patients with AS and to determine how such treatments affect symptoms, function, co-morbidities and quality of life. The study is a prospective cohort enrolling two groups of patients meeting international criteria for AS and who are naïve to biologic therapy: those commencing biologic therapy (etanercept or adalimumab) and those who are not commencing biologic therapy.

HERU researchers involved in this research project: Paul McNamee

External collaborators: G Macfarlane, G Jones (Other Applied Health Sciences, University of Aberdeen); K Hyrich, K Watson, M Lunt, D Symmons (Arthritis Research UK Epidemiology Unit, University of Manchester); R Sturrock (Centre for Rheumatic Diseases, University of Glasgow); L Kay (Freeman Hospital, Newcastle) and A Neilson (University of Edinburgh)

CATHETER II - Washout policies to prevent catheter associated complications

Randomised controlled trial comparing the clinical and cost-effectiveness of various washout policies versus no washout policy in preventing catheter associated complications in adults living with long-term catheters

Urinary catheters are soft tubes inserted into the bladder to drain urine to a collection bag or valve. Current best practice for LTC care includes educating patients on how to look after their catheter. Patients normally change their catheter bag every week while the catheter itself is changed by a nurse every 10-12 weeks. Despite this, complications such as blockages, urinary tract infections and urinary incontinence can occur with LTC use. Blockages are one of the most common complications, and can lead to urine retention, incontinence, severe pain, anxiety and the need for an emergency catheter change.

There are two broad strategies to deal with the prevention and management of catheter blockage: more frequent change of the catheter and/or the use of liquid washout solutions to flush the catheters. LTC washouts are widely used in clinical practice to prevent LTC blockage but there is limited evidence to recommend their widespread use or stoppage. In CATHETER II, participants with a LTC are being randomised to receive standard catheter care with or without weekly catheter washouts (citric acid or saline). The alternative policies will be compared on a range of outcome measures, including the number of catheter blockages; catheter-associated urinary tract infections; health-related quality of life; and costs incurred by patients and NHS.

HERU researchers involved in this research project: Graham Scotland and Mary Kilonzo

External collaborators: Abdel-Fattah, M., N'Dow, J., Murchie, P., MacLennan, S., Myint, P., Omar, I. (Institute of Applied Health Sciences, University of Aberdeen); MacLennan, G. (Health Services Research Unit (HSRU), University of Aberdeen).

C-Gall - Laparoscopic cholecystectomy for symptomatic gallstones

C-Gall: A randomised controlled trial comparing the clinical effectiveness and cost-effectiveness of laparoscopic cholecystectomy compared with observation/conservative management for preventing recurrent symptoms and complications in adults with uncomplicated symptomatic gallstones

Gallstones are common but only one in three people develop symptoms (severe abdominal pain, nausea and vomiting). These are sometimes accompanied by inflammation of the gallbladder (cholecystitis). Painkillers, anti-inflammatory medicines and antibiotics are usually prescribed initially and surgery to remove the gallbladder (cholecystectomy) is advised for medically fit patients. Approximately 70,000 cholecystectomies are performed every year in the UK, with significant costs for the NHS. However, it is known that some patients do not have any more symptoms after the initial episode of pain and that surgery might not be necessary.

This study will identify, across 20 UK hospitals, 430 patients that will be randomly allocated to either receive surgery or conservative management. Participants will be followed for 18 months and the primary outcome measure will be quality of life throughout that period (measured by the area under the curve using the SF-36 instrument).

This study will include a full economic evaluation. We will also consider a model to extend the analysis beyond the clinical follow-up period. The primary economic outcome measure will be incremental cost per QALY.

C-GALL logoC-GALL Project websites

HERU researchers involved in this research project: Rodolfo Hernández

External collaborators: I Ahmed (NHS Grampian); C Ramsay, J Norrie, K Gillies, A Avenell, M Brazzelli (HSRU, University of Aberdeen) and P Murchie (Other Applied Health Sciences, University of Aberdeen)

DIAMOND - Deep infiltrating endometriosis: management by treatment versus early surgery

Endometriosis is a chronic and often debilitating condition affecting 1 in 10 women in the UK. The condition arises when cells similar to those found in the womb are found elsewhere in the body. Each month, these cells build-up, break down and bleed causing severe symptoms such as chronic pain and infertility.

Occasionally, the endometrial cells grow deeper into tissues and organs, such as the bowel, bladder and vagina, causing a severe form of the condition called deep endometriosis (DE). DE can be treated by taking hormones such as the combined contraceptive pill, that can shrink areas of endometriosis, or by using keyhole (laparoscopic) surgery to remove areas of endometriosis.

The limited research that has been done suggests that for some women with DE who are not considering immediate pregnancy, hormonal treatment over many months could be just as effective as surgery in relieving pain. Clinical guidelines state that either hormones or surgery can be used but are unable to recommend one over the other in the absence of research directly comparing them.

Funded by the National Institute for Health Research (NIHR), the DIAMOND trial is comparing laparoscopic surgery to medical (hormonal) management for the treatment for DE. The economic evaluation will include a within trial assessment of cost-effectiveness at 18 months post randomisation, and modelling to assess cost-effectiveness up to the time of menopause.

HERU researchers involved in this research project: Graham Scotland and Charlotte Kennedy

External collaborators: Cooper, K. (NHS Grampian); Clark, J. (Birmingham Women's NHS Foundation Trust); Amer, S. (University of Nottingham); MacLennan, G., Gillies, K., Murchie, P., Bhattacharya, S. (University of Aberdeen); Byrne, D. (Royal Cornwall Hospitals NHS Trust); Cox, E. (Endometriosis UK); Gamaleldin, I. (University of Bristol); Vashisht, A. (University College London); Horne, A. (University of Edinburgh).  

EDNA - Early Detection of Neovascular Age-related macular degeneration

‘Wet’ or neovascular age-related macular degeneration (nAMD) is a leading cause of sight loss in older people. The EDNA study will evaluate five non-invasive diagnostic tests which are easily performed and routinely carried out in the NHS secondary care setting and which fall into two groups: functional and morphological.

The functional tests are visual acuity, Amsler test and self-reported quality of sight. The morphological tests are fundus examination and optical coherence tomography (OCT). The diagnostic accuracy of these tests will be assessed against a reference standard test (fluorescein angiography). The results from this prospective cohort study will be used to inform the development of a decision analytic model, which will model disease progression and the costs and consequences of using the alternative diagnostic test to monitor patients in secondary care. http://www.nets.nihr.ac.uk/projects/hta/1214207.

HERU researchers involved in this project: Graham Scotland

External collaborators: U Chakravarthy, R Hogg (Queen’s University Belfast); C Ramsay, K Bainster, J Cook, A Azuara-Blanco (HSRU, University of Aberdeen); S Sivaprasad (Moorfields Eye Hospital NHS Foundation Trust) and H Heimann (Royal Liverpool & Broadgreen University Hospitals NHS Trust).

 

E-FREEZE - Embryo transfer in women undergoing in-vitro fertilization

Despite improvements in technology, IVF success rates remain low with an overall live birth rate of 25% per treatment. Additionally, there are concerns about health outcomes for mothers and babies conceived through IVF, particularly after fresh embryo transfer, including maternal ovarian hyperstimulation syndrome (OHSS) and perinatal morbidity. It is believed that high levels of ovarian hormones during ovarian stimulation could create a relatively hostile environment for embryo implantation whilst increasing the risk of OHSS. It has been suggested that electively freezing embryos with the intention of thawing and replacing them within the uterus at a later stage (thawed frozen embryo transfer), instead of fresh embryo transfer, may lead to improved pregnancy rates and fewer complications. This two-arm parallel group randomised controlled trial, across multiple IVF centres in the UK, aims to address this question: http://www.nets.nihr.ac.uk/projects/hta/1311582.

More information on the trial is available at the Trial website and on the NIHR project portfolio. The ISRCTN registry is 61225414 (DOI: 10.1186/ISRCTN61225414).

HERU researchers involved in this research project: Graham Scotland

External collaborators: Mahashwari, A. (NHS Grampian); Macklon, N. (University of Southampton); Khalaf, Y. (Guy’s and St Thomas Hospital); Lavery, S. (Hammersmith Hospital); Child, T., Juszczak, E., Hardy, P., Kurinczuk, J. (University of Oxford); Rajkohwa, M. (Birmingham’s Women’s Hospital); Coomarasamy, A. (University of Birmingham); Cutting, R. (University of Sheffield); Brison, D. (Central Manchester University Hospital NHS Trust); Troup, S. (Liverpool Women’s Hospital); Lewis-Jones, C. (Infertility Network, UK); Raine-Fenning, N. (University of Nottingham) and Bhattacharya, S. (Obstetrics & Gynaecology, University of Aberdeen.

GRIP - Glaucoma Risk Prediction in ocular hypertension

A cohort study using electronic medical records to validate a risk predictor and determine the cost-effectiveness of different monitoring schemes according to risk of conversion to glaucoma.

Glaucoma is a common eye condition that can lead to loss of vision if not identified and treated early. One factor which can increase the chance of developing glaucoma is ocular hypertension (high eye pressure), which is usually detected during an eye health test at the optometrist. A tool which could identify those at the greatest risk of progressing from ocular hypertension to glaucoma would support clinical decision-making and patient communication.

The GRIP study, funded by the National Institute for Health Research (NIHR), aims to improve and validate an existing glaucoma risk calculator and also determine if it is worthwhile to treat people with milder eye pressure. NHS records of over 23,000 people who have ocular hypertension and have been monitored at eleven hospital eye services across the UK will be reviewed. The risk prediction tool will be evaluated for different follow-up periods.

Patients’ values and experiences regarding the management of ocular hypertension will also be explored with focus groups and interviews, and their preferences will be formally assessed in a discrete choice experiment (DCE).

There is more information on the study at the NIHR Journals Library.

HERU Researchers: Rodolfo Hernández and Verity Watson

Collaborators: A. Azuara-Blanco (Queen’s University Belfast); Y. Takwoingi (University of Birmingham); A. King (Nottingham University Hospitals NHS Trust); G. Gazzard, (Moorfields Eye Hospital NHS Foundation Trust); D. Crabb; City, University of London; J. Morgan (Cardiff University); C. Cardwell (Queen's University of Belfast).

 

i-TRAC - In-home Tracking of glaucoma: Reliability, Acceptability, and Cost

Digital technologies for home monitoring glaucoma: a feasibility study

The main aim of this study, funded by the National Institute for Health Research (NIHR), is to assess the acceptability and feasibility of home monitoring for glaucoma. Glaucoma is a common chronic eye condition and the second commonest cause of blindness in the UK. It is typically caused by the pressure in the eye (intraocular pressure) being too high. Glaucoma impairs mainly peripheral vision (the visual field).

Glaucoma patients typically receive monitoring in hospital settings and regular check-ups are required for the rest of their lives. Recent advances in technology mean it is now possible for glaucoma patients to monitor eye pressure and visual fields in their own home. However, it is not known if this is feasible and acceptable to patients.

The i-TRAC study will use a tablet device to test if home monitoring is feasible and if it is acceptable to patients. The study will also make recommendations on future research around home monitoring of glaucoma.

There is more information on the study at the NIHR Journals Library.

HERU Researcher: Rodolfo Hernández

Collaborators: K. Gillies, G. MacLennan, M. Forrest, (Health Services Research Unit, University of Aberdeen); A. Azuara-Blanco (Queen's University of Belfast)

LENS - Lowering Events in Non-proliferative retinopathy in Scotland

Diabetic retinopathy (DR) and diabetic maculopathy are common microvascular complications of diabetes mellitus. At an advanced (clinically significant) stage, these complications can lead to visual loss and blindness. While the risk of cardiovascular events in DM has been substantially reduced by various preventive strategies, there are few effective options to slow the progression of microvascular complications. However, sub-studies from two large cardiovascular trials have suggested that a drug called fenofibrate may be effective in slowing the progression of DR (measured as a composite tertiary outcome). Whilst suggestive of some benefit, these sub-studies do not provide definitive evidence.

The LENS study aims to provide better evidence by randomising 1,060 individuals, at moderate to high risk of progressing to clinically significant DR, to either fenofibrate or placebo for at least a median of four years. Participants will be followed up for progression to clinically significant DR, retinal laser therapy, vitrectomy or intra-vitreal injection of medication owing to DR, health-related quality of life, and health service resource use.

The economic evaluation will take the form of cost–utility analysis conducted alongside the trial, and modelling will be used to extrapolate longer-term cost-effectiveness if necessary.

More information on the trial is available at the NIHR project portfolio.

The trial is registered in the ISRCTN  Registry: ISRCTN15073006

HERU researchers involved in this research project: Graham Scotland

External collaborators: D Preiss, J Armitage (University of Oxford); J Olsen (NHS Grampian), J Logue, N Sattar, H Murray (University of Glasgow), G Leese and H Colhoun (University of Dundee)

MASTER - Male synthetic sling versus Artificial urinary Sphincter Trial for men with urodynamic stress incontinence after prostate surgery: Evaluation by Randomised trial

Around one in five men who undergo prostate surgery for cancer or benign disease need to use incontinence pads because of leakage of urine when they walk around, cough or do any physical exertion. This impacts upon quality of life, can lower self-esteem and productivity, and can damage personal relationships. At present the only effective surgical treatment is insertion of a plastic artificial urinary sphincter (AUS) device which involves a major operation to place an inflatable cuff around the urine pipe close to the bladder, and inflating it to prevent leakage. A new male sling has been developed which, when inserted under the urine pipe, supports the outlet of the bladder but doesn’t need a pump. It is less expensive for the NHS (around £6,000) and easier to insert, but some men may still need a subsequent operation to insert an AUS if they feel their incontinence has not improved enough. It is also uncertain whether there are other advantages or disadvantages compared to the AUS, and whether men will be as satisfied with the results.

The ISRCTN for the trial is ISRCTN49212975 and more details are available at the project website.

HERU researchers involved in this research project: Mary Kilonzo

External collaborators: P Abrams (North Bristol NHS Trust); M Drake (University of Bristol); C Glazener, J Norrie, C Ramsay, C Boachie, K McCormack, G McPherson, A McDonald (HSRU, University of Aberdeen); R Pickard (University of Newcastle upon Tyne) and N Cotterill (University of Bristol)

Oral iron, Intravenous iron or discontinuation of therapy for older adults with treatment-unresponsive iron deficiency anaemia - a pilot rct

Oral iron supplementation is the most common treatment for anaemia but it does not improve anaemia for all people and there are associated side effects. Three broad treatment strategies are possible yet there is no evidence regarding effectiveness or cost-effectiveness for them.

A pilot randomised controlled trial was undertaken to assess the feasibility of conducting a definitive comparative trial of the following three treatment options:

  1. no treatment,
  2. oral iron supplementation and
  3. intravenous iron infusion.

HERU researchers involved with this research project: Paul McNamee

External Collaborators: Myint, P. (Other Applied Health Sciences, University of Aberdeen); Witham, M., Hands, K. (Ninewells Hospital Dundee); Lee, A. (Medical Statistics Team, University of Aberdeen).

PIP - Pulpotomy for the management of irreversible pulpitis in mature teeth

Tooth decay is very common condition. Almost all adults have some decay in their back teeth. Where the tooth decay has spread deep into the nerve, and caused serious and irreversible damage, there are different treatments available. The most common treatments are to take out the tooth or use root canal treatment. Root canal treatment removes all the nerve and is very expensive, time consuming and technically demanding.

A possible alternative is to remove only the infected part of the nerve, which is an easier and quicker treatment. This technique is called pulpotomy. Research has already been conducted in children’s teeth that supports using pulpotomy instead of root canal treatment. However, there are gaps in knowledge about using pulpotomy in adult’s teeth.

The PIP clinical trial compares pulpotomy with root canal treatment in adult patients recruited from dental practices across Scotland and England. The research considers the pain experienced by patients, the impact of treatment on their lives, whether further treatment is needed due to infection and the time and financial costs incurred. Patient questionnaires, X-rays and data from dentists are used to evaluate the success of the two treatments. Dental staff and patients are also interviewed on their views on the two treatments.

HERU researchers involved in this research project: Marjon van der Pol and Dwayne Boyers

Co-Applicants: J. Clarkson - Joint Principal Investigator (University of Dundee); C. Ramsay - Joint Principal Investigator (Health Services Research Unit (HSRU), University of Aberdeen); S. Albadri, F. Jarad (University of Liverpool); A Banjeree, F. Mannocci, R. Moazzez (King's College London); D. Conway, D. Robertson (University of Glasgow); C. Deery, Z. Marshaman (University of Sheffield); A-M Glenny (University of Manchester); T. McGuff, D. Ricketts, C. Tait, T. Lamont (University of Dundee); L. Young (NHS Education for Scotland).

PROSPECT follow up - PROlapse Surgery: Pragmatic Evaluation and randomised Controlled Trial

The lifetime risk of undergoing surgery for prolapse is nearly 10%. There are several different traditional surgical techniques, none of which have been properly evaluated. The initial study embedded two large RCTs investigating different surgical techniques for two distinct patient populations of women with vaginal prolapse (primary and secondary) within a comprehensive cohort of all patients.

The economic evaluation investigated the costs and cost-effectiveness of the interventions from the perspective of the NHS and for the women and their families. Information on the cost of the intervention and the use of primary and secondary NHS services by the women (including referral for specialist management) were collected, as were personal costs to the women (such as costs of travelling to appointments and work/social restrictions).

Trial participants were asked to complete the EQ–5D at baseline and at 6, 12 and 24 months after randomisation, and responses were used to compute QALYs. In a sensitivity analysis, QALYs were also estimated from the SF–12 completed at the same time points.

Since the long-term effects of the treatments are not known, participants are being followed up over an extended period of five years. These longer-term data will be used to update model based estimates of cost-effectiveness that were previously derived by extrapolation of the data observed to 24 months. 

HERU researchers involved in this research project: Mary Kilonzo and Dwayne Boyers

External collaborators: C. Glazener, A. Grant, J. Norrie, G. MacLennan, A. McDonald, G. McPherson (Health Services Research Unit (HSRU), University of Aberdeen); A.R.B. Smith, (St. Mary’s Hospital Manchester); R.M. Freeman (Plymouth Hospital NHS Trust); C. Bain, K. Cooper (NHS Grampian); S. Hagan (Glasgow Caledonian University); I.B.G. Montgomery (Aberdeen).

PUrE - Clinical and cost-effectiveness of surgical interventions for stones in the lower pole calyces of the kidney

Kidney stone disease is very common and, although stones in the kidney do not always cause problems, most need treatment. They can cause serious problems, such as pain, infection and kidney failure, with burden to patients, the NHS and society. There are three treatment options in the NHS for stones in the lower part of the kidney: (1) flexible ureterorenoscopy with laser lithotripsy (FURS); (2) percutaneous nephrolithotomy (PNL); and (3) extracorporeal shockwave lithotripsy (ESWL). Each treatment has advantages and disadvantages (benefits and harms) and there is uncertainty about which of these treatments is best to free people from kidney stones and which is best value for patients and the NHS.

This study will randomly allocate 522 patients with smaller stones (diameter ≤ 10 mm) to be treated with either FURS or ESWL and 522 patients with larger stones (10 mm < diameter ≤ 25 mm ) to be treated with either FURS or PNL, with each participant followed up for one year.

The primary outcome is generic health status (EQ-5D-5L) area under the curve (AUC) to 12 weeks post-intervention. This study includes a full economic evaluation. A within trial analysis as well as a simple model to extend the analysis beyond the clinical study follow-up period will be considered. For further details please see: http://www.nets.nihr.ac.uk/projects/hta/1315202.

More information on the trial is available at the Trial website and on the NIHR project portfolio. The ISRCTN registry number is 98970319 (DOI: 10.1186/ISRCTN98970319)

HERU researchers involved in this research project: Rodolfo Hernández

External collaborators: S McClinton (NHS Grampian & University of Aberdeen); T Lam (University of Aberdeen); O Wiseman (Addenbrooke's NHS Trust); D Smith (University College London Hospital); B Turney (John Radcliffe Hospital NHS Trust); R Pickard (The Freeman Hospital & University of Newcastle); R Thomas, G MacLennan, J Norrie, S MacLennan, K Starr, CT Clark (HSRU, University of Aberdeen) and K Anson (St George's Healthcare NHS Trust)

RAACENO - Reducing Asthma Attacks in Children using Exhaled Nitric Oxide as a biomarker

Primary research question: Is a schedule of FeNO plus symptom treatment more efficacious in reducing asthma when compared to a symptom-only schedule? Secondary research questions: (1) Is a FeNO plus symptom treatment schedule more efficacious in improving asthma control and spirometry when compared to a symptom-only schedule? (2) Are there correlations between changes in repeated measurements of FeNO and sputum eosinophil count? (3) Is sputum eosinophilia associated with increased risk of asthma exacerbations but not asthma control over the following three months? (4) Is asthma treatment guided by symptoms plus FeNO more efficacious in reducing risk of asthma exacerbations where FeNO and sputum eosinophilia are concordant? (5) What are the relative costs, effects and cost-effectiveness of a FeNO plus symptom treatment schedule compared to a symptom-only schedule over 12 months? (6) Is FeNO plus symptom treatment acceptable to children and their parents? What are their and the research nurses’ perceptions?

More information on the project is available on the RAACENO website.

HERU researchers involved in this research project: Paul McNameeGraham Scotland

External collaborators: S Turner, H Morgan (HSRU, University of Aberdeen); S Fielding, D Price (Applied Health Sciences, University of Aberdeen); M Thomas (University of Southampton) and E Gaillard (University of Leicester)

REFLeCt trial - Fluoride toothpaste to prevent dental caries

REFLECt trial: A Randomised controlled trial to Evaluate the clinical and cost effectiveness of prescribing high concentration FLuoride toothpaste in preventing and treating dEntal Caries in high-risk older adulTs

The RELFECT study is a two arm, parallel group pragmatic open label randomised controlled trial with 36 month follow.  The trial will randomise participants from Manchester, Scotland and Northern Ireland.  The primary clinical outcome for the study is restoration or extraction due to caries.  The health economic outcomes for the study are NHS and patient perspective costs, willingness to pay and net benefit.  Two economic analyses will be completed, the first, a within trial analysis over a three year time horizon.  Discrete choice experiments will be used to value the trial outcomes within a cost-benefit analysis framework to reflect broader measures of value to patients.  The findings will be compared with a standard cost-utility analysis.  A micro-simulation modelling study will be conducted to extrapolate the findings of the trial over a participant’s lifetime.   This study will provide important information on the value of prescribing a treatment which is increasing in use, without any evidence to support its effectiveness or cost-effectiveness.

HERU researchers involved in this research project: Dwayne Boyers

External collaborators:  Tickle, M., Walsh, T., Worthington, H., Glenny, A-M., Pretty, I., Birch, S. (University of Manchester); Clarkson, J. (University of Dundee).

REGAL trial - Recurrence of endometriosis: GnRH analogues versus laparoscopic surgery

Endometriosis is a common, painful condition affecting one in ten women of childbearing age. It occurs when cells like those lining the womb grow outside it, causing internal bleeding, scarring and pain. Key hole surgery (laparoscopy) is commonly used to destroy areas of endometriosis. However, endometriosis returns in up to half of treated women within five years, and there is uncertainty about how best to treat women, particularly those who wish to preserve their fertility.

Repeat surgery is invasive, expensive and risky, without guaranteeing a cure. A less invasive treatment is monthly or three-monthly injections with Gonadotrophin Releasing hormone (GnRH) analogues. While effective in reducing pain, this type of hormonal treatment has generally only been used for up to a year because of the risk of side effects (hot flushes and night sweats) and concerns about osteoporosis. However, recent research suggests that giving small doses of hormone replacement therapy (HRT) with GnRH analogues can reduce the risk of side effects.

Funded by the National Institute for Health Research (NIHR), this trial will assess the clinical and cost-effectiveness of long-term GnRH analogues with added HRT compared to conservative key hole surgery in women who experience recurrence of pain after surgery but who wish to preserve their fertility.

HERU researchers involved in this research project: Graham Scotland

External collaborators: Saraswat, L. (NHS Grampian & University of Aberdeen); MacLennan, G., Gillies, K. (Health Services Research Unit (HSRU), University of Aberdeen); Bhattacharya, S. (Other Applied Health Sciences, University of Aberdeen).

SIMS trial - Slings in the surgical management of female stress urinary incontinence

SIMS Trial: Adjustable anchored single-incision mini-slings versus standard tension-free mid-urethral slings in the surgical management of female stress urinary incontinence: a pragmatic multicentre non-inferiority randomised controlled trial

Stress urinary incontinence (SUI) is the most common type of urinary incontinence (UI) in pre-menopausal women, accounting for almost 50% of cases. Surgical procedures for the management of female SUI have been continuously evolving over the last four decades with the ultimate aim of providing an effective and truly ambulatory surgical procedure. In the most common surgical procedure, tension-free, standard mid-urethral slings (SMUS), a synthetic mesh (tape) is placed under the urethra to add support by creating a sub-urethral hammock. An alternative procedure known as adjustable anchored single-incision mini-sling (SIMS) is designed to have advantages over tension-free SMUS in that it avoids the blind insertion trajectory into the pelvic cavity or the thigh muscles while maintaining the concept of the hammock support to the urethra. The aim of the current study is to conduct a health economic evaluation alongside a randomised controlled trial comparing these two interventions.

The SIMS Trial builds on earlier work in the SIMS pilot study

Project website for the SIMS Trial, at the Centre for Healthcare Randomised Trials.

The ISRCTN is ISRCTN93264234 

HERU researchers involved in this research project: Mary Kilonzo

External collaborators: M Abdel-Fattah, J N'Dow (Other Applied Health Sciences, University of Aberdeen); R Assassa (Mid Yorkshire Hospitals NHS Trust); G MacLennan, K McCormack, J Norrie (HSRU, University of Aberdeen); J Wardle (Continence Foundation)

UK-REBOA - Resuscitative Endovascular Balloon Occlusion of the Aorta

REBOA is currently used in a small number of trauma centres in the USA, France, Scandinavia, and Japan, and in a single centre in the UK. Whilst REBOA has shown early promise, recent observational studies have provided conflicting evidence as to its potential benefits. A robust evaluation of its feasibility, safety, efficacy and cost-effectiveness is urgently required.

The study will randomise a maximum of 120 patients from 10 large MTCs across the UK. The total sample size is constrained by the limited number of centres and the relative infrequency of trauma patients with life-threatening torso haemorrhage. Due to this constrained sample size we have adopted a Bayesian group-sequential trial design.

The study will include a full economic evaluation conducted alongside a Bayesian group-sequential randomised controlled trial. The primary economic outcome will be lifetime incremental cost per Quality Adjusted Life Year (QALY) gained, from a health care provider perspective and from a personal perspective (time to return to work or usual activities). Routine data will be collected where possible alongside the trial to estimate resource use with minimal patient burden. The 6 month follow up will include quality of life and return to normal activities questionnaires. A Markov decision analysis model will be used to extrapolate short term trial outcomes over a lifetime horizon. The project will also report data on shorter term (six month) costs to the NHS, mortality, EQ-5D-5L and extended Glasgow Outcome Score (GOS-E) at 6 month follow up. A value of information analysis will be included to assess the need for further research to address any remaining uncertainty in cost-effectiveness.

More information about this project is available on the REBOA project website.

HERU researchers involved in this research project: Dwayne Boyers

Collaborators: Prinicipal Investigators: J. Jansen and M. Campbell (University of Aberdeen)

VUE: Vault or Uterine prolapse surgery Evaluation

VUE: Vault or Uterine prolapse surgery Evaluation: two parallel randomised controlled trials of surgical options for upper compartment (uterine or vault) pelvic organ prolapse

Gynaecologists have recognised for some time that both anatomical failure and recurrence of prolapse symptoms after surgery are common: one in three women who have a prolapse operation will go on to have another, though not necessarily in the same compartment.

More recently, it has also been recognised that surgery can be followed by a greater impairment of quality of life than from the original prolapse itself (for example the development of new-onset urinary incontinence after surgery, or prolapse at a different site). Whilst anterior and posterior prolapse surgery is most common (90% of operations), around 43% of women also have a uterine (34%) or vault (9%) procedure at the same time. Indeed, this demonstrates that women who have a hysterectomy have around a 27% chance of needing a subsequent vault prolapse repair.

These data are derived from the first 700 women recruited in PROSPECT, a large HTA-funded UK RCT of anterior or posterior prolapse surgery with or without the use of mesh (HTA No. 07/60/18). In VUE, the opportunity has arose to then switch from randomising between lower compartment surgery to trials involving different surgical options for upper compartment prolapse (uterine and vault).

 

HERU researchers involved in this research project: Mary Kilonzo

External collaborators: C Glazener, S Breeman, G McPherson, A McDonald, J Norrie, A Elders (HSRU, University of Aberdeen); I.B.G. Montgomery, (University of Aberdeen); S Hagen (Glasgow Caledonian University); A.R.B. Smith (St. Mary’s Hospital Manchester); R.M Freeman (Plymouth Hospital NHS Trust); C Bain and K Cooper (NHS Grampian)

VUE - Vault or Uterine prolapse surgery Evaluation: long term follow-up

Long term follow up for VUE - Vault or Uterine prolapse surgery Evaluation: Two parallel randomised controlled trials of surgical options for upper compartment (uterine or vault) pelvic organ prolapse

Gynaecologists have recognised for some time that both anatomical failure and recurrence of prolapse symptoms after surgery are common: one in three women who have a prolapse operation will go on to have another, though not necessarily in the same compartment.

More recently, it has also been recognised that surgery can be followed by a greater impairment of quality of life than from the original prolapse itself (for example the development of new-onset urinary incontinence after surgery or prolapse at a different site). Whilst anterior and posterior prolapse surgery is most common (90% of operations), around 43% of women also have a uterine (34%) or vault (9%) procedure at the same time. Indeed, this demonstrates that women who have a hysterectomy have around a 27% chance of needing a subsequent vault prolapse repair. 

This extended follow-up of women randomised to the VUE trial is being conducted to better inform lomg-term clinical and cost – effectiveness of the alternative surgical procedures. 

HERU researchers involved in this research project: Mary Kilonzo

External collaborators: C. Glazener, S. Breeman, G. McPherson, A. McDonald, J. Norrie, A. Elders (Health Services Research Unit (HSRU), University of Aberdeen); I.B.G. Montgomery (Aberdeen); S. Hagen (Glasgow Caledonian University); A.R.B. Smith (St. Mary’s Hospital Manchester); R.M. Freeman (Plymouth Hospital NHS Trust); C. Bain, K. Cooper (NHS Grampian).

Recently Completed Projects

CLASS - Comparison of LAser, Surgery and foam Sclerotherapy

Randomised controlled trial comparing foam sclerotherapy, alone or in combination with endovenous laser therapy, with conventional surgery as a treatment for varicose veins

A randomised controlled trial comparing foam sclerotherapy, alone or in combination with endovenous laser therapy, with conventional surgery as a treatment for varicose veins. The study involves participants from hospitals throughout the UK and in addition to clinical measures, NHS and patient costs were assessed, and QALYs were derived from responses to the EQ–5D and SF–36 at baseline, six weeks and six months. Given that the initial report was based on follow-up data to six months, results were extrapolated to a longer time horizon using an economic decision analytic model. 

Outcome and translation

The trial has now completed a period of extended follow-up to five years post randomisation. Results based on this extended follow-up are are now published, and suggest that laser has the highest probability of being cost-effective at thresholds commonly applied in the UK NHS. 

HERU researchers involved with this research project: Luke Vale, Graham Scotland, Emma Tassie and Maria Dimitrova

External Collaborators: J Brittenden, K Cassar, P Bachoo, J Norrie (School of Medicine, Medical Sciences and Nutrition, University of Aberdeen); MJ Gough, IAD Mavor, J Scott (University of Leeds); P McCollum (University of Hull); IC Chetter (Hull NHS Trust); J Burr, M Campbell and C Ramsay (HSRU, University of Aberdeen)

EAGLE - Effectiveness, in Angle closure Glaucoma, of Lens Extraction

The active group had early lens extraction, i.e. cataract surgery. The control group had standard care where laser treatment was used to open drainage but did not improve sight. The outcomes were changes in quality of life; visual field; intra-ocular pressure; angle closure; need for additional medications; need for further surgery (trabeculectomy). The costs of the treatment and subsequent management for both interventions were estimated and incremental cost per QALY gained calculated, based on the responses to the EQ–5D.

Approximately 23 specialist centres in the UK, 7 centres in East Asia (from Singapore, Malaysia, Hong Kong and Taiwan), and 1 in Australia participated in this trial.

Outcome and Translation

This international, multicentre trial determined the best way of treating angle closure glaucoma, one of the main causes of blindness. The results of the study are being disseminated in a series of peer reviewed papers, keynote presentations and a lay summary.

HERU researchers involved in this research project: Graham Scotland, Mehdi Javanbakht (HERU)

External collaborators: A Azaura-Blanco, C Ramsay, J Norrie (HSRU, University of Aberdeen); T Aung (Singapore National Eye Centre); J Burr (University of St. Andrews); P Foster (UCL); D Friedman (The Johns Hopkins Hospital); J Lai (United Christian Hospital); Da-Wen Lu (Tri-Services General Hospital); C Lui (Taipei Veterans General Hospital); W Nolan (Sandwell and West Birmingham Hospital); J See (National University Hospital) and D Wong (University of Hong Kong)

International Standard Randomised Controlled Trial Number Register (ISRCTN) 44464607.

The National Institute for Health Research (NIHR) have produced an NIHR Signal for this research project.

Got-it-trial - glycerine triturate for retained placenta

Got-it-trial: A pragmatic, adaptive, sequential, placebo controlled randomised trial to determine the effectiveness of glycerine triturate for retained placenta

Retained placenta (RP) affects 2% of vaginal deliveries, which equates to nearly 11,000 women in the UK per annum, and is a major cause of post-partum haemorrhage with major obstetric haemorrhage itself affecting nearly 1 in 180 women and being the commonest cause of significant maternal morbidity.

It was hypothesised that sublingual glyceryl trinitrate (GTN) spray could reduce the need for manual removal of the placenta (MROP) following failure of the current approach to management (oxytocin and controlled cord traction). GTN was compared with placebo on outcomes measured over four interrelated domains – clinical, safety, patient-sided and economic.

The economic evaluation took the form of a cost–consequence analysis, relating differences in costs to the health service out to six weeks post-delivery with differences on the clinical, safety, and patient-sided outcomes.

Outcome and translation

The results that have now been published showed GTN to be ineffective for the management of retained placenta. There was no significant impact on health service costs. 

International Standard Randomised Controlled Trial Number Register: ISRCTN88609453

HERU researchers involved in this research project: Graham Scotland

External collaborators: F Denison, J Lawton (University of Edinburgh); J Norrie, G McPherso

HEALTH - Hysterectomy or Endometrial AbLation Trial for Heavy menstrual bleeding

A multicentre randomised controlled trial comparing laparoscopic supra-cervical hysterectomy with second generation endometrial ablation trial for the treatment of heavy menstrual bleeding

One woman in five in the UK experiences HMB, which can have a major impact on her quality of life. It is the fourth most common reason for women to attend gynaecology outpatient clinics and accounts for 20% of all gynaecology outpatient referrals. The NICE guideline on HMB recommends EA as well as hysterectomy as options for women with HMB. However, up to a quarter of women who undergo EA require subsequent gynaecological surgery and despite the demonstrated clinical and cost-effectiveness of hysterectomy, concerns remain about its invasiveness and the risks of short- and long-term morbidity associated with the procedure.

Unlike conventional hysterectomy, the more recent approach of laparoscopic supra-cervical hysterectomy (LASH) is minimally invasive, quick, relatively easy to learn and associated with low morbidity, short hospital stay (under 24 hours) and rapid recovery time. HEALTH is a multicentre randomised controlled trial (RCT) comparing LASH with second-generation EA (the current first line surgical treatment for HMB).

The trial is registered at the ISRCTN Registry: ISRCTN49013893

HERU researchers involved in this research project: Graham Scotland

External collaborators: S Bhattacharya (Other Applied Health Sciences, University of Aberdeen) K Cooper (NHS Grampian); J Clark (Birmingham Women’s Hospital); J Hawe (Countess of Chester NHS Foundation Trust); K Phillips (Hull and East Yorkshire Hospitals NHS Trust); R Hawthorne (NHS Greater Glasgow and Clyde); J Norrie and J Cook (HSRU, University of Aberdeen)

INTERVAL - Investigation of NICE Technologies for Enabling Risk-Variable-Adjusted-Length dental recalls trial

A parallel-group, randomised, controlled comparison of three forms of dental recall strategy (6-month recall, risk-based recall and 24-month recall) evaluated the effectiveness and cost-effectiveness of these dental recall strategies by assessing their impact on maintaining oral health. A cost–benefit analysis was undertaken to assess the efficiency of the alternative recall strategies. Willingness to pay was elicited using a discrete choice experiment.

Outcome and Translation

Publications are currently in development.

HERU researchers involved in this research project: Marjon van der Pol and Dwayne Boyers

External collaborators: N Pitts, J Clarkson, D Bonetti, R Freeman, D Ricketts (University of Dundee); C Ramsay, (HSRU, University of Aberdeen); H Worthington (University of Manchester); T Anderson, W McCombes, L Young (NHS Education for Scotland); F Burke, D White (University of Birmingham); G Douglas (University of Leeds); R Gorter (University of Amsterdam); R Herbert (University of Cardiff); P Hodge (University of Glasgow); G Humphris (University of St. Andrews); T Mettes (Radboud University, NIJMEJEN Medical Centre, The Netherlands); I Needleman (UCL Eastman Dental Institute) and M Ross (University of Edinburgh)

IQuaD - Improving the Quality of Dentistry

IQuaD: Improving the Quality of Dentistry: a randomised controlled trial comparing oral hygiene advice and periodontal instrumentation for the prevention and management of periodontal disease in dentate adults attending dental primary care

Periodontal disease is the most common oral disease affecting adults. This disease is preventable, yet it remains the major cause of poor oral health worldwide and is the primary cause of tooth loss in older adults. There is a lack of strong evidence to inform clinicians and policy makers of the relative effectiveness (if any) and cost-effectiveness of different types of oral hygiene advice (OHA). The economic evaluation conducted as part of this cluster randomised controlled trial elicited the costs of dental care to both the NHS and patients and equated the data with benefits to patients. Benefits to patients were estimated using a discrete choice experiment administered to a sample of the general population to provide a scoring algorithm with which to weight the outcomes for the patient participants in the trial.

Outcome and Translation

63 dental practices and 1877 participants were recruited. Under Intention To Treat (ITT) analysis there was no evidence of a difference in gingival inflammation/bleeding (the primary clinical effectiveness outcome measure) across any of the randomised groups. There was no clinical benefit from scheduling 6-monthly or 12-monthly scale and polish over not scheduling these treatments unless desired or recommended. Furthermore, there was no clinical benefit of personalised over routine oral hygiene advice in either gingival inflammation/bleeding or patient centred outcomes (including oral health related quality of life).

Compared to standard care, no scale and polish with personalised advice had the greatest NHS: -£15 (-£34 to +£4) and participant: -£64 (-£112 to -£16) cost savings. The DCE shows that the general population value these services greatly and were willing to pay for both scale and polish and personalised advice. WTP for scale and polish was higher than personalised advice. Overall, Personalised OHA with 6-monthly PI had the greatest incremental net benefit to society: +£48 (+£22 to +£74). Sensitivity analyses did not change conclusions. The results of the study provide a dilemma for NHS dental policy makers who must consider whether or not to fund services that are not clinically beneficial but are highly valued by the general population.

HERU researchers involved in this research project: Marjon van der Pol and Dwayne Boyers

External collaborators: J Clarkson, D Bonetti, N Pitts (University of Dundee); C Ramsay (HSRU, University of Aberdeen); J Burr (University of St. Andrews); H Worthington, C Jones, M Tickle (University of Manchester Dental Hospital); P Heasman, J Steele (University of Newcastle); L Young, I Madden, W McCombes (NHS Education for Scotland); P Hodge (University of Glasgow Dental School); M Ross (University of Edinburgh); D Ricketts, A Hall (Dundee Dental Care Hospital & School) and P Averley (Queensway Dental Practice)

Maintained physical activity and physiotherapy in the management of distal arm pain

The best approach to managing arm pain is unclear. Patients are often advised to rest and avoid purported harmful activities, and are commonly referred to physiotherapy. However, none of these strategies are evidence-based and there are reasons to suppose that rest may be inferior to remaining active. Well-conducted randomised trials are needed to resolve these uncertainties and to improve outcomes. This project addressed this need through the conduct of a multicentre randomised trial together with a cost–utility analysis. Project findings are currently being written up for publication.

Outcome and Translation

The results of the study will inform clinical practice over how best to manage distal arm pain.

This trial is registered on the ISRCTN Registry: ISRCTN79085082

HERU researchers involved in this research project: Paul McNamee and Aileen Neilson

External collaborators: G Jones, G Macfarlane (Other Applied Health Sciences, University of Aberdeen); K Palmer, D Coggon (University of Southampton); K Burton (University of Huddersfield); K Walker-Bone (Brighton and Sussex NHS Trust); S Lamb (University of Warwick); A McConnachie (University of Glasgow); C McCabe (University of Bath); N Shenker (Cambridge University Hospitals)

OPAL – Optimal PFMT for Adherence Long-term

OPAL – Optimal PFMT for Adherence Long-term: Multicentre randomised trial of the effectiveness and cost-effectiveness of basic versus intensive, biofeedback-assisted pelvic floor muscle training for female stress or mixed urinary incontinence

Based on previous research, current UK guidelines recommend that women with stress incontinence are offered at least three months of pelvic floor muscle exercises. These exercises are taught by a specialist physiotherapist or nurse. There is evidence that these exercises can work to strengthen the muscles and decrease leakage, but it is not clear how ‘intensively’ women have to exercise to get a good result that lasts, thus improving their quality of life and reducing the likelihood of surgery.

This research aims to find out whether the use of biofeedback can help to improve the results of the exercise training in both the short- and longer-term. We also want to find out how much urine leakage women in both groups have, how much this impacts on their lives, what other bladder problems they have, what other treatments they have had, how much exercise they did, how confident they were, and how much their muscles have strengthened. We also measure the costs of the treatments and any costs to the women and their families, and balance these costs against any benefits of the intensive treatment.

Outcome and Translation

Our aim is to establish if the addition of biofeedback to PFMT is more cost effective than PFMT alone.  The results will inform the decision makers on the cost effectiveness of the addition of biofeedback machines to  pelvic floor muscle training treatment  of women with urinary incontinence.

HERU researchers involved in this research project: Mary Kilonzo

External collaborators: S Hagen, D McClurg, J Booth (Glasgow Caledonian University); C Glazener, J Francis, J Norrie, A Elders, A McDonald, G McPherson, N Kolehmainen (HSRU, University of Aberdeen); A Wael (NHS Ayrshire and Arran); M Abdel-Fattah (Other Applied Health Sciences, University of Aberdeen); C Bugge (University of Stirling); B Buckley (Independent); S Dean (University of Exeter); H Smith (University of Otago, NZ); KL Guerrero (clinical expert) and LE Wilson (User)

International Standard Randomised Controlled Trial Number Register: ISRCTN57746448

TISU - Therapeutic Interventions for Stones of the Ureter

TISU: Therapeutic Interventions for Stones of the Ureter: a multicentre randomised controlled trial of extracorporeal shockwave lithotripsy, as first treatment option, compared with direct progression to ureteroscopic retrieval, for ureteric stones

Urinary stone disease is very common with an estimated prevalence among the general population of 2–3% (1.8 million people in the UK) with males forming stones three times as often as females. All symptomatic urinary tract stones, and ureteric stones in particular, are associated with severe pain and can have a significant impact on patients’ quality of life due to the detrimental effect on their ability to work and the need for hospitalisation. Most ureteric stones can be expected to pass spontaneously with supportive care (painkillers and fluids) possibly aided by drugs such as alpha blockers or calcium channel blockers (conservative management). However, between a fifth and a third of cases require an active intervention (stone removal) because of failure to pass the stone, continuing pain, infection or obstruction to urine drainage.

The two standard active intervention options are extracorporeal shockwave lithotripsy (ESWL) and ureteroscopic stone retrieval. Whilst both ESWL and ureteroscopy appear to be effective in terms of stone clearance they differ in terms of invasiveness, anaesthetic requirement, treatment setting, potentially the number of procedures required to clear the stone, complications, patient reported outcomes (such as severity and duration of pain after intervention, time off work and bothersome urinary symptoms), and cost. There is uncertainty around which is the most clinically effective in terms of stone clearance and the true cost to the NHS and to society (in terms of impact on patient reported health and economic burden).

Outcome and Translation

The findings of this project will inform the decision makers on the most clinical and cost- effective  surgical intervention to use in the treatment of ureteric stones. The project will also inform the national guidance on the treatment of patients that present with ureteric stones.

ISRCTN registry: ISRCTN92289221

TISU Project website (Centre for Healthcare Randomised Trials)

HERU researchers involved in this research project: Mary Kilonzo

External collaborators: S McClinton, L Kurban (NHS Grampian); J N’Dow, S MacLennan, T Lam (Academic Urology Unit, University of Aberdeen); G MacLennan, J Norrie, R Thomas, K Starr (HSRU, University of Aberdeen); F Keely (Southmead Hospital); K Anson (St Georges NHS Trust); C Clark (Service User); R Pickard (Newcastle University) and N Burgess (Norfolk and Norwich University Hospital)

Vitamin K to reduce falls in older people

Vitamin K supplementation to reduce falls in older people - a multicentre trial

Vitamin K is involved in a wide range of biological processes, including vascular, bone, neurological and muscle function. Studies in osteoporosis suggest beneficial effects on bone mineral density, and pilot data suggest that vitamin K supplementation may be able to reduce postural sway in older people – a key risk factor for falls.

This pilot randomised controlled trial tested the optimum dose (200mcg and 400mcg vs placebo) of vitamin K given for one year to improve postural sway in a group of 96 older people at high risk of falls; tested recruitment rates for a large, community-based falls trial; and collected preliminary data on falls rates to inform the sample-size calculation for a full-scale trial. The economic analysis focused on the estimation of the worth of future additional research to reduce decision uncertainty, using pre-trial modelling, and calculated the optimal sample size for a future study. 

Outcome and Translation

We found that costs were lower amongst participants in the low dose Vitamin K2 group, relative to high dose Vitamin K2 (£896-£902 versus £1033-£1044). Neither dose of vitamin K2 produced any improvement relative to placebo. The optimal sample size for a future trial would be 131 participants per group, and such a trial would remain cost-effective up to a sample size of 1100 per group.  

The trial is regsitered with the ISRCTN registry: ISRCTN18436190

The project was discussed in a HERU Blog post - Vitamin K2 has no effect on reducing the risk of falls.

HERU researchers involved in this research project: Paul McNamee

External collaborators: M. Witham, M. McMurdo, P. Donnan, (Ninewells Hospital); R. Soiza (Applied Medicine, University of Aberdeen) and V. Cvoro (Department of Geriatric Medicine, Victoria Hospital).