A multicentre randomised controlled trial of transfusion indication threshold reduction on transfusion rates, morbidity and health-care resource use following cardiac surgery (TITRe2)

Health Technology Assessment

Volumn 20, Issue 60, 2016, Pages 1-259

  Reeves, Barnaby C ^a   Pike, Katie ^a   Rogers, Chris A ^a   Brierley, Rachel C M ^a   Stokes, Elizabeth A ^b   Wordsworth, Sarah ^b   Nash, Rachel L ^a   Miles, Alice ^a   Mumford, Andrew D ^a   Cohen, Alan ^c   Angelini, Gianni D ^a   Murphy, Gavin J ^d  

^a UNIVERSITY OF BRISTOL   (United Kingdom)

^b UNIVERSITY OF OXFORD   (United Kingdom)

^c UNIVERSITY HOSPITALS BRISTOL NHS FOUNDATION TRUST   (United Kingdom)

^d UNIVERSITY OF LEICESTER   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

HEMOGLOBIN;

ACUTE KIDNEY FAILURE; ADOLESCENT; ARTICLE; BRAIN ISCHEMIA; CONTROLLED STUDY; COST CONTROL; COST EFFECTIVENESS ANALYSIS; COST UTILITY ANALYSIS; DISEASE SEVERITY; EMERGENCY SURGERY; ERYTHROCYTE TRANSFUSION; FEMALE; HEALTH CARE COST; HEALTH CARE PERSONNEL; HEART INFARCTION; HEART SURGERY; HOSPITALIZATION; HUMAN; INTENSIVE CARE; INTESTINE INFARCTION; LENGTH OF STAY; LUNG DISEASE; MAJOR CLINICAL STUDY; MALE; MORBIDITY; MORTALITY; MULTICENTER STUDY; NATIONAL HEALTH SERVICE; OUTCOME ASSESSMENT; PARALLEL DESIGN; POSTOPERATIVE CARE; POSTOPERATIVE COMPLICATION; QUALITY ADJUSTED LIFE YEAR; QUALITY OF LIFE; RANDOMIZED CONTROLLED TRIAL; REFERENCE VALUE; RESOURCE MANAGEMENT; SEPSIS; SOCIAL WORK; SURGICAL INFECTION; TREATMENT DURATION; TREATMENT INDICATION; TREATMENT RESPONSE; UNITED KINGDOM; AGED; ANEMIA; CLINICAL TRIAL; COMMUNICABLE DISEASE; COST BENEFIT ANALYSIS; ECONOMICS; ISCHEMIA; MIDDLE AGED; PROCEDURES; PROPORTIONAL HAZARDS MODEL; REPRODUCIBILITY; STATISTICAL MODEL; TIME FACTOR;

AGED; ANEMIA; COMMUNICABLE DISEASES; COST-BENEFIT ANALYSIS; ERYTHROCYTE TRANSFUSION; FEMALE; HEMOGLOBINS; HUMANS; ISCHEMIA; LENGTH OF STAY; LOGISTIC MODELS; MALE; MIDDLE AGED; POSTOPERATIVE COMPLICATIONS; PROPORTIONAL HAZARDS MODELS; QUALITY OF LIFE; QUALITY-ADJUSTED LIFE YEARS; REPRODUCIBILITY OF RESULTS; TIME FACTORS; UNITED KINGDOM;

EID: 84983735924     PISSN: 13665278     EISSN: 20464924     Source Type: Journal    
DOI: 10.3310/hta20600     Document Type: Article

References (81)

1. Habib RH, Zacharias A, Schwann TA, Riordan CJ, Engoren M, Durham SJ, et al. Role of hemodilutional anemia and transfusion during cardiopulmonary bypass in renal injury after coronary revascularization: implications on operative outcome. Crit Care Med 2005;33:1749-56. http://dx.doi.org/10.1097/01.CCM.0000171531.06133.B0
2. Murphy GJ, Reeves BC, Rogers CA, Rizvi SI, Culliford L, Angelini GD. Increased mortality, postoperative morbidity, and cost after red blood cell transfusion in patients having cardiac surgery. Circulation 2007;116:2544-52. http://dx.doi.org/10.1161/CIRCULATIONAHA.107.698977
3. Karkouti K, Wijeysundera DN, Beattie WS. Risk associated with preoperative anemia in cardiac surgery: a multicenter cohort study. Circulation 2008;117:478-84. http://dx.doi.org/10.1161/ CIRCULATIONAHA.107.718353
4. Bennett-Guerrero E, Zhao Y, O’Brien SM, Ferguson TB Jr, Peterson ED, Gammie JS, et al. Variation in use of blood transfusion in coronary artery bypass graft surgery. JAMA 2010;304:1568-75. http://dx.doi.org/10.1001/jama.2010.1406
5. Murphy MF, Murphy GJ, Gill R, Herbertson M, Allard S, Grant-Casey J. National Comparative Audit of Blood Transfusion: 2011 Audit of Blood Transfusion in Adult Cardiac Surgery. Birmingham:NHS; 2013. URL: http://hospital.blood.co.uk/media/26859/nca-2011_use_of_blood_in_adult_ cardiac_surgery_report.pdf (accessed 30 July 2015).
6. Wells AW, Llewelyn CA, Casbard A, Johnson AJ, Amin M, Ballard S, et al. The EASTR Study:indications for transfusion and estimates of transfusion recipient numbers in hospitals supplied by the National Blood Service. Transfus Med 2009;19:315-28. http://dx.doi.org/10.1111/j.1365-3148. 2009.00933.x
7. Brierley RCM, Pike K, Miles A, Wordsworth S, Stokes EA, Mumford AD, et al. A multi-centre randomised controlled trial of Transfusion Indication Threshold Reduction on transfusion rates, morbidity and healthcare resource use following cardiac surgery: study protocol. Transfus Apher Sci 2014;50:451-61. http://dx.doi.org/10.1016/j.transci.2014.02.020
8. Corwin HL, Parsonnet KC, Gettinger A. RBC transfusion in the ICU. Is there a reason? Chest 1995;108:767-71. http://dx.doi.org/10.1378/chest.108.3.767
9. Stover EP, Siegel LC, Parks R, Levin J, Body SC, Maddi R, et al. Variability in transfusion practice for coronary artery bypass surgery persists despite national consensus guidelines: a 24-institution study. Institutions of the Multicenter Study of Perioperative Ischemia Research Group. Anesthesiology 1998;88:327-33. http://dx.doi.org/10.1097/00000542-199802000-00009
10. Koch CG, Li L, Duncan AI, Mihaljevic T, Cosgrove DM, Loop FD, et al. Morbidity and mortality risk associated with red blood cell and blood-component transfusion in isolated coronary artery bypass grafting. Crit Care Med 2006;34:1608-16. http://dx.doi.org/10.1097/01.CCM.0000217920.48559.D8
11. Karkouti K, Wijeysundera DN, Yau TM, McCluskey SA, Chan CT, Wong PY, et al. Influence of erythrocyte transfusion on the risk of acute kidney injury after cardiac surgery differs in anemic and nonanemic patients. Anesthesiology 2011;115:523-30. http://dx.doi.org/10.1097/ ALN.0b013e318229a7e8
12. Carson JL, Carless PA, Hebert PC. Transfusion thresholds and other strategies for guiding allogeneic red blood cell transfusion. Cochrane Database Syst Rev 2012;4:CD002042. http://dx.doi.org/10.1002/14651858.cd002042.pub3
13. Carson JL, Terrin ML, Noveck H, Sanders DW, Chaitman BR, Rhoads GG, et al. Liberal or restrictive transfusion in high-risk patients after hip surgery. N Engl J Med 2011;365:2453-62. http://dx.doi. org/10.1056/NEJMoa1012452
14. Carson JL, Brooks MM, Abbott JD, Chaitman B, Kelsey SF, Triulzi DJ, et al. Liberal versus restrictive transfusion thresholds for patients with symptomatic coronary artery disease. Am Heart J 2013;165:964-71. http://dx.doi.org/10.1016/j.ahj.2013.03.001
15. Carson JL, Carless PA, Hebert PC. Outcomes using lower vs higher hemoglobin thresholds for red blood cell transfusion. JAMA 2013;309:83-4. http://dx.doi.org/10.1001/jama.2012.50429
16. Bolton-Maggs PHB, Poles D, Watt A, Thomas D, Cohen H, on behalf of the Serious Hazards of Transfusion (SHOT) Steering Group. The 2012 Annual SHOT Report. 2013. URL: www.shotuk.org/ wp-content/uploads/2013/08/SHOT-Annual-Report-2012.pdf (accessed 30 July 2015).
17. Greinacher A, Fendrich K, Brzenska R, Kiefel V, Hoffmann W. Implications of demographics on future blood supply: a population-based cross-sectional study. Transfusion 2011;51:702-9. http://dx.doi.org/10.1111/j.1537-2995.2010.02882.x
18. Shander A, Hofmann A, Ozawa S, Theusinger OM, Gombotz H, Spahn DR. Activity-based costs of blood transfusions in surgical patients at four hospitals. Transfusion 2010;50:753-65. http://dx.doi.org/10.1111/j.1537-2995.2009.02518.x
19. Ferraris VA, Brown JR, Despotis GJ, Hammon JW, Reece TB, Saha SP, et al. 2011 update to the Society of Thoracic Surgeons and the Society of Cardiovascular Anesthetists blood conservation clinical practice guidelines. Ann Thorac Surg 2011;91:944-82. http://dx.doi.org/10.1016/ j.athoracsur.2010.11.078
20. Napolitano LM, Kurek S, Luchette FA, Anderson GL, Bard MR, Bromberg W, et al. Clinical practice guideline: red blood cell transfusion in adult trauma and critical care. Crit Care Med 2009;37:3124-57. http://dx.doi.org/10.1097/CCM.0b013e3181b39f1b
21. Carson JL, Grossman BJ, Kleinman S, Tinmouth AT, Marques MB, Fung MK, et al. Red blood cell transfusion: a clinical practice guideline from the AABB*. Ann Intern Med 2012;157:49-58. http://dx.doi.org/10.7326/0003-4819-157-1-201206190-00429
22. World Health Organization (WHO). Global Forum for Blood Safety: Patient Blood Management. Priorities for Action. Dubai: WHO; 2011. URL: www.who.int/bloodsafety/events/gfbs_01_pbm/en/ (accessed 24 February 2014).
23. Farmer SL, Towler SC, Leahy MF, Hofmann A. Drivers for change: Western Australia Patient Blood Management Program (WA PBMP), World Health Assembly (WHA) and Advisory Committee on Blood Safety and Availability (ACBSA). Best Pract Res Clin Anaesthesiol 2013;27:43-58. http://dx.doi.org/10.1016/j.bpa.2012.12.007
24. Johnson RG, Thurer RL, Kruskall MS, Sirois C, Gervino EV, Critchlow J, et al. Comparison of two transfusion strategies after elective operations for myocardial revascularization. J Thorac Cardiovasc Surg 1992;104:307-14.
25. Bracey AW, Radovancevic R, Riggs SA, Houston S, Cozart H, Vaughn WK, et al. Lowering the hemoglobin threshold for transfusion in coronary artery bypass procedures: effect on patient outcome. Transfusion 1999;39:1070-7. http://dx.doi.org/10.1046/j.1537-2995.1999.39101070.x
26. Murphy GJ, Rizvi SIA, Battaglia F, Culliford L, Rogers CA, Cohen A, et al. A pilot randomized controlled trial of the effect of transfusion- threshold reduction on transfusion rates and morbidity after cardiac surgery. Transfus Altern Transfus Med 2007;9(Suppl. 1):41-2.
27. Wilson AP, Treasure T, Sturridge MF, Gruneberg RN. A scoring method (ASEPSIS) for postoperative wound infections for use in clinical trials of antibiotic prophylaxis. Lancet 1986;1:311-13. http://dx.doi.org/10.1016/S0140-6736(86)90838-X
28. Wilson AP, Weavill C, Burridge J, Kelsey MC. The use of the wound scoring method ‘ASEPSIS’ in postoperative wound surveillance. J Hosp Infect 1990;16:297-309. http://dx.doi.org/10.1016/0195-6701(90)90002-6
29. Gibbons C, Bruce J, Carpenter J, Wilson AP, Wilson J, Pearson A, et al. Identification of risk factors by systematic review and development of risk-adjusted models for surgical site infection. Health Technol Assess 2011;15(30). http://dx.doi.org/10.3310/hta15300
30. Mehta RL, Kellum JA, Shah SV, Molitoris BA, Ronco C, Warnock DG, et al. Acute Kidney Injury Network: report of an initiative to improve outcomes in acute kidney injury. Crit Care 2007;11:R31. http://dx.doi.org/10.1186/cc5713
31. EuroQol Group. EuroQol - a new facility for the measurement of health-related quality of life. Health Policy 1990;16:199-208. http://dx.doi.org/10.1016/0168-8510(90)90421-9
32. Cohen J. Statistical Power Analysis for the Behavioral Sciences. 2nd edn. New Jersey, NJ: Lawrence Erlbaum Associates; 1988.
33. Pike K, Brierley R, Rogers CA, Murphy GJ, Reeves BC. Adherence in a randomised controlled trial comparing liberal and restrictive red blood cell (RBC) transfusion protocols after cardiac surgery (TITRe2). Trials 2011;12(Suppl. 1):A131. http://dx.doi.org/10.1186/1745-6215-12-S1-A131
34. Pike K, Nash RL, Murphy GJ, Reeves BC, Rogers CA. Transfusion Indication Threshold Reduction (TITRe2) randomised controlled trial in cardiac surgery: statistical analysis plan. Trials 2015;16:54. http://dx.doi.org/10.1186/s13063-015-0564-x
35. Tooze JA, Grunwald GK, Jones RH. Analysis of repeated measures data with clumping at zero. Stat Methods Med Res 2002;11:341-55. http://dx.doi.org/10.1191/0962280202sm291ra
36. Englberger L, Suri RM, Li Z, Casey ET, Daly RC, Dearani JA, et al. Clinical accuracy of RIFLE and Acute Kidney Injury Network (AKIN) criteria for acute kidney injury in patients undergoing cardiac surgery. Crit Care 2011;15:R16. http://dx.doi.org/10.1186/cc9960
37. Hajjar LA, Vincent JL, Galas FR, Nakamura RE, Silva CM, Santos MH, et al. Transfusion requirements after cardiac surgery: the TRACS randomized controlled trial. JAMA 2010;304:1559-67. http://dx.doi.org/10.1001/jama.2010.1446
38. Shehata N, Burns LA, Nathan H, Hebert P, Hare GM, Fergusson D, et al. A randomized controlled pilot study of adherence to transfusion strategies in cardiac surgery. Transfusion 2012;52:91-9. http://dx.doi.org/10.1111/j.1537-2995.2011.03236.x
39. Patel NN, Avlonitis VS, Jones HE, Reeves BC, Sterne JAC, Murphy GJ. Indications for red cell transfusion in cardiac surgery: a systematic review and meta-analysis of randomized controlled trials and observational studies [published online ahead of print 16 November 2015]. Lancet Haematol 2015. http://dx.doi.org/10.1016/S2352-3026(15)00198-2
40. Schulz KF, Grimes DA. Multiplicity in randomised trials I: endpoints and treatments. Lancet 2005;365:1591-5. http://dx.doi.org/10.1016/S0140-6736(05)66461-6
41. NICE. Social Value Judgements: Principles for the Development of NICE Guidance. 2nd edn. London:NICE; 2008. URL: www.nice.org.uk/media/default/About/what-we-do/Research-and-development/Social-Value-Judgements-principles-for-the-development-of-NICE-guidance.pdf (accessed 30 July 2015).
42. Drummond MF, Jefferson TO. Guidelines for authors and peer reviewers of economic submissions to the BMJ. The BMJ Economic Evaluation Working Party. BMJ 1996;313:275-83. http://dx.doi.org/10.1136/bmj.313.7052.275
43. Drummond MF, Sculpher MJ, Torrance GW, O’Brien BJ, Stoddart GL. Methods for the Economic Evaluation of Health Care Programmes. 3rd edn. New York, NY: Oxford University Press; 2005.
44. NICE. Guide to the Methods of Technology Appraisal 2013. London: NICE; 2013. URL: www.nice.org.uk/article/pmg9/resources/non-guidance-guide-to-the-methods-of-technology-appraisal-2013-pdf (accessed 30 July 2015).
45. Department of Health. National Schedule of Reference Costs 2012-13. London: Department of Health; 2013.
46. NHS Blood and Transplant. NHS Blood and Transplant Price List 2012-2013. 2012. URL: http://hospital.blood.co.uk/products/ (accessed 28 September 2012).
47. Department of Health Commercial Medicines Unit. Electronic Marketing Information Tool (eMIT). Drugs and Pharmaceutical Electronic Market Information (eMit). URL: http://cmu.dh.gov.uk/electronic-market-information-tool-emit/ (accessed 10 February 2014).
48. Joint Formulary Committee. British National Formulary. 66 edn. London: BMJ Group and Pharmaceutical Press; 2013.
49. Curtis L. Unit Costs of Health and Social Care 2013. Canterbury, University of Kent: Personal Social Services Research Unit; 2013.
50. Dolan P, Gudex C, Kind P, Williams A. A Social Tariff for Euroqol: Results from a UK General Population Survey. York: University of York; 1995.
51. White IR, Royston P, Wood AM. Multiple imputation using chained equations: issues and guidance for practice. Stat Med 2011;30:377-99. http://dx.doi.org/10.1002/sim.4067
52. Rubin DB. Multiple Imputation For Non-Response In Surveys. New York, NY: John Wiley & Sons; 1987.
53. Manca A, Hawkins N, Sculpher MJ. Estimating mean QALYs in trial-based cost-effectiveness analysis: the importance of controlling for baseline utility. Health Econ 2005;14:487-96. http://dx.doi.org/10.1002/hec.944
54. Dakin HA, Wordsworth S, Rogers CA, Abangma G, Raftery J, Harding SP, et al. Cost-effectiveness of ranibizumab and bevacizumab for age-related macular degeneration: 2-year findings from the IVAN randomised trial. BMJ Open 2014;4:e005094. http://dx.doi.org/10.1136/bmjopen-2014-005094
55. Murphy GJ, Pike K, Rogers CA, Wordsworth S, Stokes EA, Angelini GD, et al. Liberal or restrictive transfusion after cardiac surgery. N Engl J Med 2015;372:997-1008. http://dx.doi.org/10.1056/NEJMoa1403612
56. Davies L, Brown TJ, Haynes S, Payne K, Elliott RA, McCollum C. Cost-effectiveness of cell salvage and alternative methods of minimising perioperative allogeneic blood transfusion:a systematic review and economic model. Health Technol Assess 2006;10(44). http://dx.doi.org/10.3310/hta10440
57. Joint Formulary Committee. British National Formulary. 58 edn. London: BMJ Group and Pharmaceutical Press; 2009.
58. Briggs A, Clark T, Wolstenholme J, Clarke P. Missing … presumed at random: cost-analysis of incomplete data. Health Econ 2003;12:377-92. http://dx.doi.org/10.1002/hec.766
59. Greenland S. An introduction to instrumental variables for epidemiologists. Int J Epidemiol 2000;29:1102. http://dx.doi.org/10.1093/oxfordjournals.ije.a019909
60. Dzik W. Fresh blood for everyone? Balancing availability and quality of stored RBCs. Transfus Med 2008;18:260-5. http://dx.doi.org/10.1111/j.1365-3148.2008.00870.x
61. von Elm E, Altman DG, Egger M, Pocock SJ, Gøtzsche PC, Vandenbroucke JP, et al. The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement:guidelines for reporting observational studies. J Clin Epidemiol 2008;61:344-9. http://dx.doi.org/10.1016/j.jclinepi.2007.11.008
62. Hebert PC, Wells G, Blajchman MA, Marshall J, Martin C, Pagliarello G, et al. A multicenter, randomized, controlled clinical trial of transfusion requirements in critical care. Transfusion Requirements in Critical Care Investigators, Canadian Critical Care Trials Group. N Eng J Med 1999;340:409-17. http://dx.doi.org/10.1056/NEJM199902113400601
63. Reeves BC, Murphy GJ. Increased mortality, morbidity, and cost associated with red blood cell transfusion after cardiac surgery. Curr Opin Cardiol 2008;23:607-12. http://dx.doi.org/10.1097/ HCO.0b013e328310fc95
64. Koch CG, Li L, Sessler DI, Figueroa P, Hoeltge GA, Mihaljevic T, et al. Duration of red-cell storage and complications after cardiac surgery. N Engl J Med 2008;358:1229-39. http://dx.doi.org/10.1056/NEJMoa070403
65. Blue Book Online. How Many [Cardiac Surgery] Operations are Carried Out Each Year? 2013. URL: http://bluebook.scts.org (accessed 30 July 2015).
66. Villanueva C, Colomo A, Bosch A, Concepción M, Hernandez-Gea V, Aracil C, et al. Transfusion strategies for acute upper gastrointestinal bleeding. N Engl J Med 2013;368:11-21. http://dx.doi. org/10.1056/NEJMoa1211801
67. Task Force on Myocardial Revascularisation of the European Society of Cardiology (ESC) and the European Association for Cardio-Thoracic Surgery (EACTS), European Association for Percutaneous Cardiovascular Interventions (EAPCI), Wijns W, Kolh P, Danchin N, Di Mario C, et al. Guidelines on myocardial revascularization. Eur Heart J 2010;31:2501-55. http://dx.doi.org/10.1093/ eurheartj/ehq277
68. Joint Task Force on the Management of Valvular Heart Disease of the European Society of Cardiology (ECS), European Association for Cardio-Thoracic Surgery (EACTS), Vahanian A, Alfieri O, Andreotti F, et al. Guidelines on the management of valvular heart disease (version 2012). Eur Heart J 2012;33:2451-96. http://dx.doi.org/10.1093/eurheartj/ehs109
69. Casutt M, Seifert B, Pasch T, Schmid ER, Turina MI, Spahn DR. Factors influencing the individual effects of blood transfusions on oxygen delivery and oxygen consumption. Crit Care Med 1999;27:2194-200. http://dx.doi.org/10.1097/00003246-199910000-00021
70. Utoh J, Moriyama S, Okamoto K, Kunitomo R, Hara M, Kitamura N. The effects of cardiopulmonary bypass on postoperative oxygen metabolism. Surg Today 1999;29:28-33. http://dx.doi.org/10.1007/BF02482966
71. Wells AW, Mounter PJ, Chapman CE, Stainsby D, Wallis JP. Where does blood go? Prospective observational study of red cell transfusion in north England. BMJ 2002;325:803. http://dx.doi.org/10.1136/bmj.325.7368.803
72. Clinical Trials Registry. Transfusion Requirements in Cardiac Surgery III (TRICS-III). URL: http://clinicaltrials.gov/show/NCT02042898 (accessed 30 July 2015).
73. Lacroix J, Hébert P, Fergusson D, Tinmouth A, Blajchman MA, Callum J, et al. The Age of Blood Evaluation (ABLE) randomized controlled trial: study design. Transfus Med Rev 2011;25:197-205. http://dx.doi.org/10.1016/j.tmrv.2011.03.001
74. Lacroix J, Hébert PC, Fergusson DA, Tinmouth A, Cook DJ, Marshall JC, et al. Age of transfused blood in critically ill adults. N Engl J Med 2015;372:1410-18. http://dx.doi.org/10.1056/ NEJMoa1500704
75. Joint Formulary Committee. British National Formulary. 47 edn. London: BMJ Group and Pharmaceutical Press; 2004.
76. Lord J, Willis S, Eatock J, Tappenden P, Trapero-Bertran M, Miners A, et al. Economic modelling of diagnostic and treatment pathways in National Institute for Health and Care Excellence clinical guidelines: the Modelling Algorithm Pathways in Guidelines (MAPGuide) project. Health Technol Assess 2013;17(58). http://dx.doi.org/10.3310/hta17580
77. Gray AJ, Goodacre S, Newby DE, Masson MA, Sampson F, Dixon S, et al., on behalf of the 3CPO study investigators. A multicentre randomised controlled trial of the use of continuous positive airway pressure and non-invasive positive pressure ventilation in the early treatment of patients presenting to the emergency department with severe acute cardiogenic pulmonary oedema:the 3CPO trial. Health Technol Assess 2009;13(33). http://dx.doi.org/10.3310/hta13330
78. NICE. NICE Medical Technology Guidance 8: The VeriQ System for Assessing Graft Flow During Coronary Artery Bypass Graft Surgery. 2011. URL: http://guidance.nice.org.uk/mtg8 (accessed 30 July 2015).
79. NICE. Nutrition Support in Adults: Oral Nutrition Support, Enteral Tube Feeding and Parenteral Nutrition. Costing Report. Implementing NICE Guidance in England. NICE Clinical Guideline no. 32. 2006. URL: www.nice.org.uk/guidance/cg32/resources/costing-report-194884669 (accessed 10 November 2015).
80. NHS Business Services Authority, NHS Prescription Services. Drug Tariff. The Electronic Drug Tariff. Department of Health; 2014. URL: www.ppa.org.uk/ppa/edt_intro.htm (accessed 21 February 2014).
81. NHS Direct National Health Services Trust. NHS Direct National Health Services Trust Annual Report and Accounts 2012/13. London: The Stationery Office; 2013. URL: www.gov.uk/government/publications/nhs-direct-national-health-service-trust-annual-report-and-accounts-2012-to-2013 (accessed 30 July 2015).