Neuroleptics in the treatment of aggressive challenging behaviour for people with intellectual disabilities: a randomised controlled trial (NACHBID).

OBJECTIVE(S) To assess the effects and cost-effectiveness of haloperidol, risperidone and placebo on aggressive challenging behaviour in adults with intellectual disability. DESIGN A double-blind randomised controlled trial of two drugs and placebo administered in flexible dosage, with full, independent assessments of aggressive and aberrant behaviour, global improvement, carer burden, quality of life and adverse drug effects at baseline, 4, 12 and 26 weeks, and comparison of total care costs in the 6 months before and after randomisation. At 12 weeks, patients were given the option of leaving the trial or continuing until 26 weeks. Assessments of observed aggression were also carried out with key workers at weekly intervals throughout the trial. SETTING Patients were recruited from all those being treated by intellectual disability services in eight sites in England, one in Wales and one in Queensland, Australia. PARTICIPANTS Patients from all severity levels of intellectual disability; recruitment was extended to include those who may have been treated with neuroleptic drugs in the past. EXCLUSION CRITERIA treatment with depot neuroleptics/another form of injected neuroleptic medication within the last 3 months; continuous oral neuroleptic medication within the last week; those under a section of the Mental Health Act 1983 or Queensland Mental Health Act 2000. INTERVENTIONS Randomisation to treatment with haloperidol (a typical neuroleptic drug), risperidone (an atypical neuroleptic drug) or placebo using a permuted blocks procedure. Dosages were: haloperidol 1.25-5.0 mg daily; risperidone 0.5-2.0 mg daily. MAIN OUTCOME MEASURES Primary: reduction in aggressive episodes between baseline and 4 weeks using Modified Overt Aggression Scale. Secondary: Aberrant Behaviour Checklist; Uplift/Burden Scale; 40-item Quality of Life Questionnaire; Udvalg for Kliniske Undersøgelser scale; Clinical Global Impressions scale. Economic costs recorded using a modified version of Client Service Receipt Inventory for 6 months before and after randomisation. RESULTS There were considerable difficulties in recruitment because of ethical and consent doubts. Twenty-two clinicians recruited a total of 86 patients. Mean daily dosages were 1.07 mg rising to 1.78 mg for risperidone and 2.54 mg rising to 2.94 mg for haloperidol. Aggression declined dramatically with all three treatments by 4 weeks, with placebo showing the greatest reduction (79%, versus 57% for combined drugs) (p = 0.06). Placebo-treated patients showed no evidence of inferior response in comparison to patients receiving neuroleptic drugs. An additional study found that clinicians who had not participated in clinical trials before were less likely to recruit. Mean total cost of accommodation, services, informal care and treatment over the 6 months of the trial was 16,336 pounds for placebo, 17,626 pounds for haloperidol and 18,954 pounds for risperidone. CONCLUSIONS There were no significant important benefits conferred by treatment with risperidone or haloperidol, and treatment with these drugs was not cost-effective. While neuroleptic drugs may be of value in the treatment of aggressive behaviour in some patients with intellectual disability, the underlying pathology needs to be evaluated before these are given. The specific diagnostic indications for such treatment require further investigation. Prescription of low doses of neuroleptic drugs in intellectual disability on the grounds of greater responsiveness and greater liability to adverse effects also needs to be re-examined.

[1]  L. Curtis,et al.  Unit Costs of Health and Social Care 2016 , 2015 .

[2]  D. Branford A study of the prescribing for people with learning disabilities living in the community and in National Health Service care. , 2008, Journal of intellectual disability research : JIDR.

[3]  D. Clarke,et al.  Psychotropic drugs and mental retardation: 1. Disabilities and the prescription of drugs for behaviour and for epilepsy in three residential settings. , 2008, Journal of mental deficiency research.

[4]  M. Pitt,et al.  Systematic review and economic analysis of the comparative effectiveness of different inhaled corticosteroids and their usage with long-acting beta2 agonists for the treatment of chronic asthma in children under the age of 12 years. , 2008, Health technology assessment.

[5]  D. Murphy,et al.  Risperidone, haloperidol, and placebo in the treatment of aggressive challenging behaviour in patients with intellectual disability: a randomised controlled trial , 2008, The Lancet.

[6]  D Elbourne,et al.  Recruitment to randomised trials: strategies for trial enrollment and participation study. The STEPS study. , 2007, Health technology assessment.

[7]  M. Crawford,et al.  Modified Overt Aggression Scale (MOAS) for People with Intellectual Disability and Aggressive Challenging Behaviour: A Reliability Study , 2007 .

[8]  R. Poole,et al.  Influence of drug company authorship and sponsorship on drug trial outcomes. , 2007, The British journal of psychiatry : the journal of mental science.

[9]  P. Jones,et al.  Cost-effectiveness of first- v. second-generation antipsychotic drugs: results from a randomised controlled trial in schizophrenia responding poorly to previous therapy. , 2007, The British journal of psychiatry : the journal of mental science.

[10]  Peter Tyrer,et al.  Comparison of alternative methods of collection of service use data for the economic evaluation of health care interventions. , 2007, Health economics.

[11]  Daniel Polsky,et al.  Economic Evaluation in Clinical Trials , 2007 .

[12]  P. Tyrer,et al.  Nidotherapy in practice , 2007 .

[13]  S. Cooper,et al.  Mental ill-health in adults with intellectual disabilities: prevalence and associated factors , 2007, British Journal of Psychiatry.

[14]  D. Symmons,et al.  A comparison of the cost-effectiveness of five strategies for the prevention of non-steroidal anti-inflammatory drug-induced gastrointestinal toxicity: a systematic review with economic modelling. , 2006, Health technology assessment.

[15]  Robert Jones,et al.  Practitioner consensus in the use of cognitive behaviour therapy for individuals with a learning disability , 2006, Journal of intellectual disabilities : JOID.

[16]  S. Paisley,et al.  Psychological therapies including dialectical behaviour therapy for borderline personality disorder: a systematic review and preliminary economic evaluation. , 2006, Health technology assessment.

[17]  E. Kaltenthaler,et al.  COMPUTERISED COGNITIVE BEHAVIOUR THERAPY FOR DEPRESSION AND ANXIETY , 2002 .

[18]  Jennifer A. Roberts,et al.  Health benefits of antiviral therapy for mild chronic hepatitis C: randomised controlled trial and economic evaluation. , 2006, Health technology assessment.

[19]  R. Murray,et al.  Randomised controlled trials of conventional antipsychotic versus new atypical drugs, and new atypical drugs versus clozapine, in people with schizophrenia responding poorly to, or intolerant of, current drug treatment. , 2006, Health technology assessment.

[20]  Simon Finfer,et al.  SAFE (The Saline versus Albumin Fluid Evaluation) 試験 , 2006 .

[21]  M. Pitt,et al.  Surveillance of Barrett's oesophagus: exploring the uncertainty through systematic review, expert workshop and economic modelling. , 2006, Health technology assessment.

[22]  Stephen Palmer,et al.  Topotecan, pegylated liposomal doxorubicin hydrochloride and paclitaxel for second-line or subsequent treatment of advanced ovarian cancer: a systematic review and economic evaluation. , 2006, Health technology assessment.

[23]  C. Clar,et al.  Clinical and cost-effectiveness of autologous chondrocyte implantation for cartilage defects in knee joints: systematic review and economic evaluation. , 2005, Health technology assessment.

[24]  C. Bull,et al.  Newborn screening for congenital heart defects: a systematic review and cost-effectiveness analysis. , 2005, Health technology assessment.

[25]  M. Pitt,et al.  The effectiveness and cost-effectiveness of dual-chamber pacemakers compared with single-chamber pacemakers for bradycardia due to atrioventricular block or sick sinus syndrome: systematic review and economic evaluation. , 2005, Health technology assessment.

[26]  M. Sculpher,et al.  Is hydrotherapy cost-effective? A randomised controlled trial of combined hydrotherapy programmes compared with physiotherapy land techniques in children with juvenile idiopathic arthritis. , 2005, Health technology assessment.

[27]  J. Lieberman,et al.  Effectiveness of antipsychotic drugs in patients with chronic schizophrenia. , 2005, The New England journal of medicine.

[28]  D. Symmons,et al.  The British Rheumatoid Outcome Study Group (BROSG) randomised controlled trial to compare the effectiveness and cost-effectiveness of aggressive versus symptomatic therapy in established rheumatoid arthritis. , 2005, Health technology assessment.

[29]  D. Lamping,et al.  An evaluation of the costs, effectiveness and quality of renal replacement therapy provision in renal satellite units in England and Wales. , 2005, Health technology assessment.

[30]  R Garside,et al.  The effectiveness and cost-effectiveness of pimecrolimus and tacrolimus for atopic eczema: a systematic review and economic evaluation. , 2005, Health technology assessment.

[31]  D G Altman,et al.  Indirect comparisons of competing interventions. , 2005, Health technology assessment.

[32]  Martin Knapp,et al.  A comparison of two methods of collecting economic data in primary care. , 2005, Family practice.

[33]  J Raftery,et al.  Clinical and cost-effectiveness of newer immunosuppressive regimens in renal transplantation: a systematic review and modelling study. , 2005, Health technology assessment.

[34]  M Sculpher,et al.  Clinical effectiveness, tolerability and cost-effectiveness of newer drugs for epilepsy in adults: a systematic review and economic evaluation. , 2005, Health technology assessment.

[35]  C Fraser,et al.  Laparoscopic surgery for inguinal hernia repair: systematic review of effectiveness and economic evaluation. , 2005, Health technology assessment.

[36]  C. Beverley,et al.  Clinical and cost-effectiveness of electroconvulsive therapy for depressive illness, schizophrenia, catatonia and mania: systematic reviews and economic modelling studies. , 2005, Health technology assessment.

[37]  P Barton,et al.  Cervical screening programmes: can automation help? Evidence from systematic reviews, an economic analysis and a simulation modelling exercise applied to the UK. , 2005, Health technology assessment.

[38]  M Knapp,et al.  Measurement of health-related quality of life for people with dementia: development of a new instrument (DEMQOL) and an evaluation of current methodology. , 2005, Health technology assessment.

[39]  A. Grant,et al.  Improving the referral process for familial breast cancer genetic counselling: findings of three randomised controlled trials of two interventions. , 2005, Health technology assessment.

[40]  C. Fowler,et al.  Randomised evaluation of alternative electrosurgical modalities to treat bladder outflow obstruction in men with benign prostatic hyperplasia. , 2005, Health technology assessment.

[41]  L. Thorpe,et al.  Short- and long-term efficacy and safety of risperidone in adults with disruptive behavior disorders , 2005, Psychopharmacology.

[42]  P Wainwright,et al.  Virtual outreach: a randomised controlled trial and economic evaluation of joint teleconferenced medical consultations. , 2004, Health technology assessment.

[43]  A. Silman,et al.  Supplementation of a home-based exercise programme with a class-based programme for people with osteoarthritis of the knees: a randomised controlled trial and health economic analysis. , 2004, Health technology assessment.

[44]  S. Ebrahim,et al.  Provision, uptake and cost of cardiac rehabilitation programmes: improving services to under-represented groups. , 2004, Health technology assessment.

[45]  N. Waugh,et al.  Pegylated interferon alpha-2a and -2b in combination with ribavirin in the treatment of chronic hepatitis C: a systematic review and economic evaluation. , 2004, Health technology assessment.

[46]  M Sculpher,et al.  Clopidogrel used in combination with aspirin compared with aspirin alone in the treatment of non-ST-segment-elevation acute coronary syndromes: a systematic review and economic evaluation. , 2004, Health technology assessment.

[47]  A Haycox,et al.  Coronary artery stents: a rapid systematic review and economic evaluation. , 2004, Health technology assessment.

[48]  M. Mugford,et al.  The Social Support and Family Health Study: a randomised controlled trial and economic evaluation of two alternative forms of postnatal support for mothers living in disadvantaged inner-city areas. , 2004, Health technology assessment.

[49]  A. Round,et al.  Effectiveness and cost-effectiveness of imatinib for first-line treatment of chronic myeloid leukaemia in chronic phase: a systematic review and economic analysis. , 2004, Health technology assessment.

[50]  S. Mason,et al.  EVALUATE hysterectomy trial: a multicentre randomised trial comparing abdominal, vaginal and laparoscopic methods of hysterectomy. , 2004, Health technology assessment.

[51]  J. Dretzke,et al.  Autoantibody testing in children with newly diagnosed type 1 diabetes mellitus. , 2004, Health technology assessment.

[52]  Anita Patel,et al.  The cost-effectiveness of mirtazapine versus paroxetine in treating people with depression in primary care , 2004, International clinical psychopharmacology.

[53]  M Sculpher,et al.  A rapid and systematic review and economic evaluation of the clinical and cost-effectiveness of newer drugs for treatment of mania associated with bipolar affective disorder. , 2004, Health technology assessment.

[54]  J Gabbay,et al.  Involving consumers in research and development agenda setting for the NHS: developing an evidence-based approach. , 2004, Health technology assessment.

[55]  A. Thompson,et al.  Improving the evaluation of therapeutic interventions in multiple sclerosis: development of a patient-based measure of outcome. , 2004, Health technology assessment.

[56]  K. Morgan,et al.  Psychological treatment for insomnia in the regulation of long-term hypnotic drug use. , 2004, Health technology assessment.

[57]  M. Westwood,et al.  Systematic review of the clinical effectiveness and cost-effectiveness of capecitabine (Xeloda) for locally advanced and/or metastatic breast cancer. , 2004, Health technology assessment.

[58]  B. Cooper,et al.  Systematic review of isolation policies in the hospital management of methicillin-resistant Staphylococcus aureus: a review of the literature with epidemiological and economic modelling. , 2003, Health technology assessment.

[59]  T. Sensky,et al.  Principles of Nidotherapy in the Treatment of Persistent Mental and Personality Disorders , 2003, Psychotherapy and Psychosomatics.

[60]  D. Janowsky,et al.  Effects of Topiramate on Aggressive, Self-Injurious, and Disruptive/Destructive Behaviors in the Intellectually Disabled: An Open-Label Retrospective Study , 2003, Journal of clinical psychopharmacology.

[61]  F. Song,et al.  Evaluating non-randomised intervention studies. , 2003, Health technology assessment.

[62]  P. Roderick,et al.  The cost-effectiveness of screening for Helicobacter pylori to reduce mortality and morbidity from gastric cancer and peptic ulcer disease: a discrete-event simulation model. , 2003, Health Technology Assessment.

[63]  O. Ukoumunne A comparison of confidence interval methods for the intraclass correlation coefficient in cluster randomized trials , 2002, Statistics in medicine.

[64]  L. Sandler Risperidone in children with autism and serious behavioral problems. , 2002, The New England journal of medicine.

[65]  N. Waugh,et al.  Screening for gestational diabetes: a systematic review and economic evaluation. , 2002, Health technology assessment.

[66]  S. Wessely,et al.  A systematic review of controlled trials of the effectiveness and cost-effectiveness of brief psychological treatments for depression. , 2002, Health technology assessment.

[67]  R. Novaco,et al.  Cognitive-behavioural treatment of anger intensity among offenders with intellectual disabilities , 2002 .

[68]  David R. Jones,et al.  A systematic review of discharge arrangements for older people. , 2002, Health technology assessment.

[69]  S. Cooray,et al.  Difficulties in conducting a randomized controlled trial of health service interventions in intellectual disability: implications for evidence-based practice. , 2002, Journal of intellectual disability research : JIDR.

[70]  E Berry,et al.  The cost-effectiveness of magnetic resonance angiography for carotid artery stenosis and peripheral vascular disease: a systematic review. , 2002, Health technology assessment.

[71]  H. Costello,et al.  Reliability and validity of the Mini PAS-ADD for assessing psychiatric disorders in adults with intellectual disability. , 2002, Journal of intellectual disability research : JIDR.

[72]  C. McDougle,et al.  Methodological issues in designing a multisite trial of risperidone in children and adolescents with autism. , 2001, Journal of child and adolescent psychopharmacology.

[73]  C. Czoski-Murray,et al.  Extended scope of nursing practice: a multicentre randomised controlled trial of appropriately trained nurses and pre-registration house officers in pre-operative assessment in elective general surgery. , 2001, Health technology assessment.

[74]  P. Garthwaite,et al.  Statistical assessment of the learning curves of health technologies. , 2001, Health technology assessment.

[75]  S. Gray,et al.  Barriers to participation in randomised controlled trials. , 2001, Journal of clinical epidemiology.

[76]  A Briggs,et al.  Economic evaluation and clinical trials: size matters , 2000, BMJ : British Medical Journal.

[77]  M. Mugford,et al.  Ultrasound screening in pregnancy: a systematic review of the clinical effectiveness, cost-effectiveness and women's views. , 2000, Health technology assessment.

[78]  P. Sandercock,et al.  Framework for design and evaluation of complex interventions to improve health , 2000, BMJ : British Medical Journal.

[79]  W. Fraser Three decades after Penrose , 2000, British Journal of Psychiatry.

[80]  R. Prescott,et al.  Barriers to participation in randomised controlled trials: a systematic review. , 1999, Journal of clinical epidemiology.

[81]  A. Glenny,et al.  Antimicrobial prophylaxis in colorectal surgery: a systematic review of randomized controlled trials , 1998, Health technology assessment.

[82]  M J Al,et al.  Sample size calculation in economic evaluations. , 1998, Health economics.

[83]  A. Mortimer,et al.  Prospective study into factors associated with aggressive incidents in psychiatric acute admission wards , 1998, British Journal of Psychiatry.

[84]  S. Cooper,et al.  Prevalence and Cluster Typology of Maladaptive Behaviours in a Geographically Defined Population of Adults with Learning Disabilities , 1996, British Journal of Psychiatry.

[85]  D. Reeves,et al.  The use of anti-psychotic drugs with adults with learning disabilities and challenging behaviour. , 1995, Journal of intellectual disability research : JIDR.

[86]  J. Peuskens Risperidone in the Treatment of Patients with Chronic Schizophrenia: a Multi-National, Multi-Centre, Double-Blind, Parallel-Group Study versus Haloperidol , 1995, British Journal of Psychiatry.

[87]  M. Aman,et al.  Factor validity and norms for the Aberrant Behavior Checklist in a community sample of children with mental retardation , 1992, Journal of autism and developmental disorders.

[88]  Douglas G. Altman,et al.  Practical statistics for medical research , 1990 .

[89]  O. Linaker Frequency of and Determinants for Psychotropic Drug Use in an Institution for the Mentally Retarded , 1990, British Journal of Psychiatry.

[90]  R. Pruchno The Effects of Help Patterns on the Mental Health of Spouse Caregivers , 1990, Research on aging.

[91]  S. Wilson Methods for the economic evaluation of health care programmes , 1987 .

[92]  U. Ahlfors,et al.  The UKU side effect rating scale: A new comprehensive rating scale for psychotropic drugs and a cross‐sectional study of side effects in neuroleptic‐treated patients , 1987, Acta psychiatrica Scandinavica. Supplementum.

[93]  M. Aman,et al.  The aberrant behavior checklist: a behavior rating scale for the assessment of treatment effects. , 1985, American journal of mental deficiency.

[94]  L. Hollister,et al.  Treatment of schizophrenic reactions with phenothiazine derivatives. A comparative study of chlorpromazine, triflupromazine, mepazine, prochlorperazine, perphenazine, and phenobarbital. , 1960, The American journal of psychiatry.

[95]  H. Bair,et al.  Efficacy of chlorpromazine in hyperactive mentally retarded children. , 1955, A.M.A. archives of neurology and psychiatry.

[96]  G. ter Riet,et al.  Methods of prediction and prevention of pre-eclampsia: systematic reviews of accuracy and effectiveness literature with economic modelling. , 2008, Health technology assessment.

[97]  S. Deb,et al.  Using medication to manage behaviour problems among adults with a learning disability , 2006 .

[98]  P. Willner The effectiveness of psychotherapeutic interventions for people with learning disabilities: a critical overview. , 2005, Journal of intellectual disability research : JIDR.

[99]  H. Williams,et al.  Randomised controlled multiple treatment comparison to provide a cost-effectiveness rationale for the selection of antimicrobial therapy in acne. , 2005, Health technology assessment.

[100]  R. Collins,et al.  Towards evidence-based guidelines for the prevention of venous thromboembolism: systematic reviews of mechanical methods, oral anticoagulation, dextran and regional anaesthesia as thromboprophylaxis. , 2005, Health technology assessment.

[101]  C. Normand,et al.  A systematic review of the role of bisphosphonates in metastatic disease. , 2004, Health technology assessment.

[102]  M K Campbell,et al.  Systematic review of the long-term effects and economic consequences of treatments for obesity and implications for health improvement. , 2004, Health technology assessment.

[103]  P F Sharp,et al.  The value of digital imaging in diabetic retinopathy. , 2003, Health technology assessment.

[104]  David R. Jones,et al.  A systematic review and evaluation of the use of tumour markers in paediatric oncology: Ewing's sarcoma and neuroblastoma. , 2003, Health technology assessment.

[105]  J Cowan,et al.  Clinical and cost-effectiveness of capecitabine and tegafur with uracil for the treatment of metastatic colorectal cancer: systematic review and economic evaluation. , 2003, Health technology assessment.

[106]  T P Klassen,et al.  The inclusion of reports of randomised trials published in languages other than English in systematic reviews. , 2003, Health technology assessment.

[107]  P. Royle,et al.  Literature searching for clinical and cost-effectiveness studies used in health technology assessment reports carried out for the National Institute for Clinical Excellence appraisal system. , 2003, Health technology assessment.

[108]  J. Wight,et al.  Treatments for spasticity and pain in multiple sclerosis: a systematic review. , 2003, Health technology assessment.

[109]  J Chilcott,et al.  A review of the clinical effectiveness and cost-effectiveness of routine anti-D prophylaxis for pregnant women who are rhesus-negative. , 2003, Health technology assessment.

[110]  A Haycox,et al.  Early thrombolysis for the treatment of acute myocardial infarction: a systematic review and economic evaluation. , 2003, Health technology assessment.

[111]  S. Stearns,et al.  Systematic review of the effectiveness and cost-effectiveness, and economic evaluation, of home versus hospital or satellite unit haemodialysis for people with end-stage renal failure. , 2003, Health technology assessment.

[112]  A. Grant,et al.  Systematic review of the clinical effectiveness and cost-effectiveness of tension-free vaginal tape for treatment of urinary stress incontinence. , 2003, Health technology assessment.

[113]  A. Bagnall,et al.  Effectiveness and cost-effectiveness of acute hospital-based spinal cord injuries services: systematic review. , 2003, Health technology assessment.

[114]  S. Paisley,et al.  Clinical and cost-effectiveness of new and emerging technologies for early localised prostate cancer: a systematic review. , 2003, Health technology assessment.

[115]  S. Eckstein The ethical conduct of research on the mentally incapacitated , 2003 .

[116]  K. Payne,et al.  Which anaesthetic agents are cost-effective in day surgery? Literature review, national survey of practice and randomised controlled trial. , 2002, Health technology assessment.

[117]  J A Kanis,et al.  Treatment of established osteoporosis: a systematic review and cost-utility analysis. , 2002, Health technology assessment.

[118]  R. Milne,et al.  Zanamivir for the treatment of influenza in adults: a systematic review and economic evaluation. , 2002, Health technology assessment.

[119]  R. Milne,et al.  Clinical effectiveness and cost-effectiveness of growth hormone in children: a systematic review and economic evaluation. , 2002, Health technology assessment.

[120]  S. Bryan,et al.  Fludarabine as second-line therapy for B cell chronic lymphocytic leukaemia: a technology assessment. , 2002, Health technology assessment.

[121]  P. Royle,et al.  Screening for hepatitis C among injecting drug users and in genitourinary medicine clinics: systematic reviews of effectiveness, modelling study and national survey of current practice. , 2002, Health technology assessment.

[122]  G. Goodwin,et al.  Bipolar disorder: clinical uncertainty, evidence-based medicine and large-scale randomised trials. , 2001, The British journal of psychiatry. Supplement.

[123]  T. Skinner,et al.  Effects of educational and psychosocial interventions for adolescents with diabetes mellitus: a systematic review. , 2001, Health technology assessment.

[124]  P. Barry,et al.  Comparison of the effectiveness of inhaler devices in asthma and chronic obstructive airways disease: a systematic review of the literature. , 2001, Health technology assessment.

[125]  M. Knapp,et al.  Home treatment for mental health problems: a systematic review. , 2001, Health technology assessment.

[126]  R. Fitzpatrick,et al.  Issues in methodological research: perspectives from researchers and commissioners. , 2001, Health technology assessment.

[127]  C. Eiser,et al.  Quality-of-life measures in chronic diseases of childhood. , 2001, Health technology assessment.

[128]  T. Peters,et al.  Subgroup analyses in randomised controlled trials: quantifying the risks of false-positives and false-negatives. , 2001, Health technology assessment.

[129]  P. Whiting,et al.  A rapid and systematic review of the clinical effectiveness and cost-effectiveness of debriding agents in treating surgical wounds healing by secondary intention. , 2001, Health technology assessment.

[130]  S. Walters,et al.  Costs and benefits of community postnatal support workers: a randomised controlled trial. , 2000, Health technology assessment.

[131]  M. McDonagh,et al.  A rapid and systematic review of the effectiveness and cost-effectiveness of the taxanes used in the treatment of advanced breast and ovarian cancer. , 2000, Health technology assessment.

[132]  K Tolley,et al.  The effectiveness of domiciliary health visiting: a systematic review of international studies and a selective review of the British literature. , 2000, Health technology assessment.

[133]  F. Cowan,et al.  Implantable contraceptives (subdermal implants and hormonally impregnated intrauterine systems) versus other forms of reversible contraceptives: two systematic reviews to assess relative effectiveness, acceptability, tolerability and cost-effectiveness. , 2000, Health technology assessment.

[134]  Williams Je,et al.  Intrathecal pumps for giving opioids in chronic pain: a systematic review. , 2000, Health technology assessment.

[135]  A. Culyer,et al.  False-negative results in screening programmes: systematic review of impact and implications. , 2000, Health technology assessment.

[136]  K. Jolly,et al.  Coronary artery stents in the treatment of ischaemic heart disease: a rapid and systematic review. , 2000, Health technology assessment.

[137]  E Berry,et al.  Intravascular ultrasound-guided interventions in coronary artery disease: a systematic literature review, with decision-analytic modelling, of outcomes and cost-effectiveness. , 2000, Health technology assessment.

[138]  P. Bower,et al.  Randomised controlled trial of non-directive counselling, cognitive-behaviour therapy and usual general practitioner care in the management of depression as well as mixed anxiety and depression in primary care. , 2000, Health technology assessment.

[139]  M. Gulliford,et al.  Monitoring blood glucose control in diabetes mellitus: a systematic review. , 2000, Health technology assessment.

[140]  R. Milne,et al.  Disease-modifying drugs for multiple sclerosis: a rapid and systematic review. , 2000, Health technology assessment.

[141]  C. Normand,et al.  Screening for sickle cell disease and thalassaemia: a systematic review with supplementary research. , 2000, Health technology assessment.

[142]  Ann Netten,et al.  Unit Costs of Health and Social Care 2002 , 2000 .

[143]  N. Waugh,et al.  Combination therapy (interferon alfa and ribavirin) in the treatment of chronic hepatitis C: a rapid and systematic review. , 2000, Health technology assessment.

[144]  M. McDonagh,et al.  A rapid and systematic review of the clinical effectiveness and cost-effectiveness of glycoprotein IIb/IIIa antagonists in the medical management of unstable angina. , 2000, Health technology assessment.

[145]  A. Culyer,et al.  Screening for hypercholesterolaemia versus case finding for familial hypercholesterolaemia: a systematic review and cost-effectiveness analysis. , 2000, Health technology assessment.

[146]  David R. Jones,et al.  Bayesian methods in health technology assessment: a review. , 2000, Health technology assessment.

[147]  A. Culyer,et al.  Liquid-based cytology in cervical screening: a rapid and systematic review. , 2000, Health technology assessment.

[148]  R. Jordan,et al.  Treatments for fatigue in multiple sclerosis: a rapid and systematic review. , 2000, Health technology assessment.

[149]  D. Ashby,et al.  An introduction to statistical methods for health technology assessment. , 2000, Health technology assessment.

[150]  Fraser Wi Three decades after Penrose. , 2000 .

[151]  T. Sheldon,et al.  What role for statins? A review and economic model. , 1999, Health technology assessment.

[152]  E. A. Nelson,et al.  Systematic reviews of wound care management: (2). Dressings and topical agents used in the healing of chronic wounds. , 1999, Health technology assessment.

[153]  A. Glenny,et al.  Antimicrobial prophylaxis in total hip replacement: a systematic review. , 1999, Health technology assessment.

[154]  J Gabbay,et al.  'Early warning systems' for identifying new healthcare technologies. , 1999, Health technology assessment.

[155]  A. Culyer,et al.  A systematic literature review of spiral and electron beam computed tomography: with particular reference to clinical applications in hepatic lesions, pulmonary embolus and coronary artery disease. , 1999, Health technology assessment.

[156]  David R. Jones,et al.  Methods for the analysis of quality-of-life and survival data in health technology assessment. , 1999, Health technology assessment.

[157]  A E Ades,et al.  Antenatal and neonatal haemoglobinopathy screening in the UK: review and economic analysis. , 1999, Health technology assessment.

[158]  A. Culyer,et al.  Effectiveness and efficiency of methods of dialysis therapy for end-stage renal disease: systematic reviews. , 1998, Health technology assessment.

[159]  M. Smith,et al.  Systematic review of endoscopic ultrasound in gastro-oesophageal cancer. , 1998, Health Technology Assessment.

[160]  M J Buxton,et al.  Evaluating patient-based outcome measures for use in clinical trials. , 1998, Health technology assessment.

[161]  M. Petticrew,et al.  Resource allocation for chronic stable angina: a systematic review of effectiveness, costs and cost-effectiveness of alternative interventions. , 1998, Health technology assessment.

[162]  R. Moore,et al.  Postoperative analgesia and vomiting, with special reference to day-case surgery: a systematic review. , 1998, Health technology assessment.

[163]  E. Murphy,et al.  Qualitative research methods in health technology assessment: a review of the literature. , 1998, Health technology assessment.

[164]  D. Spiegelhalter,et al.  Consensus development methods, and their use in clinical guideline development. , 1998, Health technology assessment.

[165]  J A Brebner,et al.  When and how to assess fast-changing technologies: a comparative study of medical applications of four generic technologies. , 1997, Health technology assessment.

[166]  A. Culyer,et al.  Newborn screening for inborn errors of metabolism: a systematic review. , 1997, Health technology assessment.

[167]  M Forshaw,et al.  A critical review of the role of neonatal hearing screening in the detection of congenital hearing impairment. , 1997, Health technology assessment.

[168]  J Nicholl,et al.  Routine preoperative testing: a systematic review of the evidence. , 1997, Health technology assessment.

[169]  A. Knowles DIABETIC FOOT ULCERATION , 1996 .

[170]  S. Cohen,et al.  Clinical and economic aspects of risperidone treatment in adults with mental retardation and behavioral disturbance. , 1996, Psychopharmacology bulletin.

[171]  J. Mansell,et al.  Severe Learning Disabilities and Challenging Behaviours: Designing high quality services , 1994 .

[172]  M. Reichman,et al.  Rating aggression in the clinical setting. A retrospective adaptation of the Overt Aggression Scale: preliminary results. , 1991, The Journal of neuropsychiatry and clinical neurosciences.

[173]  S. Yudofsky,et al.  The Overt Aggression Scale: overview and guiding principles. , 1991, The Journal of neuropsychiatry and clinical neurosciences.

[174]  C. Gutheil,et al.  The measurement of aggressive behavior: reflections on the use of the Overt Aggression Scale and the Modified Overt Aggression Scale. , 1991, The Journal of neuropsychiatry and clinical neurosciences.

[175]  J. Endicott,et al.  The Overt Aggression Scale for the objective rating of verbal and physical aggression. , 1986, The American journal of psychiatry.

[176]  S. Rothman,et al.  The Willowbrook Wars , 1984 .