Advertisement

Pharmacy World & Science

, Volume 30, Issue 2, pp 154–160 | Cite as

Measuring health-related quality of life in drug clinical trials: is it given due importance?

  • Ramón San MiguelEmail author
  • Ana María López-González
  • Eduardo Sanchez-Iriso
  • Javier Mar
  • Juan M. Cabasés
Review Paper

Abstract

Aim of the review Efficacy estimations of drug clinical trials have been based on clinical measurements and survival rates. However, advances in psychometric techniques have allowed to incorporate a new dimension based on quality of life. Questionnaires aimed at measuring patients’ health status outlook, now enable us to quantify the loss of quality of life caused by disease and the improvement that can be achieved by pharmacological treatments. The Aim of this study is to make a quantitative evaluation of the use of health related quality of life (HRQL) measures in drug clinical trials. Methods A systematic review was performed, in duplicate, of the five journals with highest contribution to the ACP Journal Club, i.e. New England Journal of Medicine, JAMA, The Lancet, Annals of Internal Medicine and the British Medical Journal. HRQL measures were evaluated in published articles referring to drug clinical trials. Results We identified 193 articles that reported the results of clinical trials, of which 28 included QOL measures as secondary end points and two as primary end points: in total, these comprised 16% of the articles analysed. Discussion Without considering the relevance of HRQL measures as a tool in the allocation of resources, it should be included as a health outcome dimension in drug clinical trials. The absence of this evaluation in studies about chronic diseases that affects patients’ daily life activities would not be justified. Conclusions HRQL measures are not used on a regular basis in drug clinical trials that are reported in the relevant literature. Systematic incorporation of QOL measures into clinical trials would make it possible to measure the benefit obtained from drug treatments taking into account the patients’ perceptions. Moreover, it would encourage the development of prospective cost-effectiveness studies with patient recorded data in the context of clinical trials. Our findings have a direct impact on practice. Being conscious of the low use of HRQL in clinical trials, it could contribute to increase the demand for these measures by health care professionals. The manuscript is also a useful tool to identify where basic concepts about HRQL measures can be found.

Keywords

Health related quality of life Quality of life Clinical trial Pharmacoeconomics 

Notes

Acknowledgements

The authors thank Dr. Carlos Aguilar and Dr. Valentín del Villar (Hospital of Soria) for their valuable help in drafting this manuscript.

References

  1. 1.
    Talbot LA, Morrell CH, Metter EJ, Fleg JL. Comparison of cardiorespiratory fitness versus leisure time physical activity as predictors of coronary events in men aged <or = 65 years and >65 years. Am J Cardiol 2002;89:1187–92.PubMedCrossRefGoogle Scholar
  2. 2.
    Walsh JME, Pignone M. Drug treatment of hyperlipidemia in women. JAMA 2004;291:2243–52.PubMedCrossRefGoogle Scholar
  3. 3.
    Testa MA, Simonson DC. Current concepts: assessment of quality-of-life outcomes. N Engl J Med 1996;334:835–40.CrossRefGoogle Scholar
  4. 4.
    Murray CJ, Lopez AD. Global mortality, disability, and the contribution of risk factors: Global burden of disease study. Lancet 1997;349:1436–42.PubMedCrossRefGoogle Scholar
  5. 5.
    Hobart J. Measuring disease impact in disabling neurological conditions: are patients’ perspectives and scientific rigor compatible? Curr Opin Neurol 2002;15:721–4.PubMedCrossRefGoogle Scholar
  6. 6.
    Mar J, Rueda JR, Durán-Cantolla J, Schechter C, Chilcott J. The cost-effectiveness of nCPAP treatment in patients with moderate-to-severe obstructive sleep apnoea. Eur Respir J 2003;21:515–22.PubMedGoogle Scholar
  7. 7.
    Patrick DL. What constitutes quality of life? Concepts and dimens Clin Nutr 1988;7:53–63.Google Scholar
  8. 8.
    Wood RW, Diehr P, Wolcott BW, Slay L, Tompkins RK. Reproducibility of clinical data and decisions in the management of upper respiratory illnesses: a comparison of physicians and non-physician providers. Med Care 1979;17:767–79.PubMedCrossRefGoogle Scholar
  9. 9.
    Guyatt GH, Veldhuyzen Van Zanten SJ, Feeny DH, Patrick DL. Measuring quality of life in clinical trials: a taxonomy and review. CMAJ 1989;140:1441–8.PubMedGoogle Scholar
  10. 10.
    Ware JE, Sherbourne CD. The MOS 36–item short-form health survey (SF-36): conceptual ramework and item selection. Med Care 1992;30:473–58.PubMedCrossRefGoogle Scholar
  11. 11.
    EuroQol group. EuroQol––A new facility for the measurement of health related quality of life. Health Policy 1990;16:199–208.Google Scholar
  12. 12.
    Hunt SM, McEwen J, McKenna SP. Measure health status. London: Croom Helm; 1986.Google Scholar
  13. 13.
    Bergner M, Bobbitt RA, Pollard WE, Marin DP, Gilson BS. The sickness impact profile. Validation of a health status measure. Med Care 1976;14:57–67.PubMedCrossRefGoogle Scholar
  14. 14.
    Jones PW. St. George’s respiratory questionnaire: MCID. COPD 2005;2:75–9.PubMedCrossRefGoogle Scholar
  15. 15.
    Marks GB, Dunn SM, Woolcock AJ. A scale for the measurement of quality of life in adults with asthma. J Clin Epidemiol 1992;45:461–72.PubMedCrossRefGoogle Scholar
  16. 16.
    Wu AW, Hays RD, Kelly S, Malitz F, Bozzette SA. Applications of the medical outcomes study health-related quality of life measures in HIV/AIDS. Qual Life Res 1997;6:531–54.PubMedCrossRefGoogle Scholar
  17. 17.
    Mitchell A, Guyatt G, Singer J, Irvine EJ, Goodacre R, Tompkins C, et al. Quality of life in patients with inflammatory bowel disease. J Clin Gastroenterol 1988;10:306–10.PubMedCrossRefGoogle Scholar
  18. 18.
    Mahoney FI, Barthel DW. Functional evaluation: the Barthel index. Md Med J 1965;14:61–5.Google Scholar
  19. 19.
    Aaronson NK, Ahmedzai S, Bergman B, Bullinger M, Cull A, Duez NJ, et al. The european organization for research and treatment of cancer QLQ-C30: a quality-of-life instrument for use in international clinical trials in oncology. J Natl Cancer Inst 1993;85:365–76.PubMedCrossRefGoogle Scholar
  20. 20.
    Guyatt GH, Osoba D, Wu AW, Wyrwich KW, Norman GR, The Clinical Significance Consensus Meeting Group. Mayo Clin Proc 2002;77:371–83.Google Scholar
  21. 21.
    Gold MR, Patrick DL, Torrance GW, et al. Identifying and valuing outcomes. In: Gold MR, Siegel JE, Russell LB, Weinstein MC. Cost-effectiveness in health and medicine. New York: Oxford University Press; 1996.Google Scholar
  22. 22.
    National Institute for Clinical Excellence. Guide to the methods of technology appraisal. London: NICE; 2004.Google Scholar
  23. 23.
    Pearson SD, Rawlins MD. Quality, innovation, and value for money: NICE and the British National Health Service. JAMA 2005;294:2618–22.PubMedCrossRefGoogle Scholar
  24. 24.
    Henry DA, Hill SR, Harris A. Drug prices and value for money: the Australian Pharmaceutical Benefits Scheme. JAMA 2005;294:2630–2.PubMedCrossRefGoogle Scholar
  25. 25.
    Sackett DL, Straus SE, Richardson WS, Rosenber W, Haynes RB. Medicina basada en la evidencia [Evidence-Based Medicine]. Hardcourt: Madrid; 2001.Google Scholar
  26. 26.
    The Wegener’s Granulomatosis Etanercept Trial (WGET) Research Group. Etanercept plus standard therapy for Wegener’s granulomatosis. N Engl J Med 2005;352:351–61.CrossRefGoogle Scholar
  27. 27.
    Mayer SA, Brun NC, Begtrup K, Broderick J, Davis S, Diringer MN, et al. Recombinant activated factor VII for acute intracerebral hemorrhage. N Engl J Med 2005;352:777–85.PubMedCrossRefGoogle Scholar
  28. 28.
    Gilron I, Bailey JM, Tu D, Holden RR, Weaver DF, Houlden RL. Morphine, gabapentin, or their combination for neuropathic pain. N Engl J Med 2005;352:1324–34.PubMedCrossRefGoogle Scholar
  29. 29.
    Boushey HA, Sorkness CA, King TS, Sullivan SD, Fahy JV, Lazarus SC, et al. Daily versus as-needed corticosteroids for mild persistent asthma. N Engl J Med 2005;352:1519–28.PubMedCrossRefGoogle Scholar
  30. 30.
    Singh BN, Singh SN, Reda DJ, Tang XC, Lopez B, Harris CL, et al. Amiodarone versus sotalol for atrial fibrillation. N Engl J Med 2005;352:1861–72.PubMedCrossRefGoogle Scholar
  31. 31.
    Korzenik JR, Dieckgraefe BK, Valentine JF, Hausman DF, Gilbert MJ. Sargramostim for active Crohn’s disease. N Engl J Med 2005;352:2193–201.PubMedCrossRefGoogle Scholar
  32. 32.
    Oxman MN, Levin MJ, Johnson GR, Schmader KE, Straus SE, Gelb LD, et al. A vaccine to prevent herpes zoster and postherpetic neuralgia in older adults. N Engl J Med 2005;352:2271–84.PubMedCrossRefGoogle Scholar
  33. 33.
    Martin M, Pienkowski T, Mackey J, Pawlicki M, Guastalla JP, Weaver C, et al. Adjuvant docetaxel for node-positive breast cancer. N Engl J Med 2005;352:2302–13.PubMedCrossRefGoogle Scholar
  34. 34.
    Feagan BG, Greenberg GR, Wild G, Fedorak RN, Pare P, McDonald JW, et al. Treatment of ulcerative colitis with a humanized antibody to the alpha4beta7 integrin. N Engl J Med 2005;352:2499–507.PubMedCrossRefGoogle Scholar
  35. 35.
    Crowther CA, Hiller JE, Moss JR, McPhee AJ, Jeffries WS, Robinson JS. Effect of treatment of gestational diabetes mellitus on pregnancy outcomes. N Engl J Med 2005;352:2477–86.PubMedCrossRefGoogle Scholar
  36. 36.
    Winton T, Livingston R, Johnson D, Rigas J, Johnston M, Butts C, et al. Vinorelbine plus cisplatin vs. observation in resected non-small-cell lung cancer. N Engl J Med 2005;352:2589–97.PubMedCrossRefGoogle Scholar
  37. 37.
    Twelves C, Wong A, Nowacki MP, Abt M, Burris H 3rd, Carrato A, et al. Capecitabine as adjuvant treatment for stage III colon cancer. N Engl J Med 2005;352:2696–704.PubMedCrossRefGoogle Scholar
  38. 38.
    Shepherd FA, Rodrigues Pereira J, Ciuleanu T, Tan EH, Hirsh V, Thongprasert S, et al. Erlotinib in previously treated non-small-cell lung cancer. N Engl J Med 2005;353:123–32.PubMedCrossRefGoogle Scholar
  39. 39.
    Reid IR, Miller P, Lyles K, Fraser W, Brown JP, Saidi Y, et al. Comparison of a single infusion of zoledronic acid with risedronate for Paget’s disease. N Engl J Med 2005;353:898–908.CrossRefGoogle Scholar
  40. 40.
    Genovese MC, Becker JC, Schiff M, Luggen M, Sherrer Y, Kremer J, et al. N Engl J Med 2005;353:1114–23.Google Scholar
  41. 41.
    Bradley TD, Logan AG, Kimoff RJ, Series F, Morrison D, Ferguson K, et al. Continuous positive airway pressure for central sleep apnea and heart failure. N Engl J Med 2005;353:2025–33.PubMedCrossRefGoogle Scholar
  42. 42.
    Demedts M, Behr J, Buhl R, Costabel U, Dekhuijzen R, Jansen HM, et al. High-dose acetylcysteine in idiopathic pulmonary fibrosis. N Engl J Med 2005;353:2229–42.PubMedCrossRefGoogle Scholar
  43. 43.
    Rabe KF, Bateman ED, O’Donnell D, Witte S, Bredenbroker D, Bethke TD. Roflumilast-an oral anti-inflammatory treatment for chronic obstructive pulmonary disease: a randomised controlled trial. Lancet 2005;366:563–71.PubMedCrossRefGoogle Scholar
  44. 44.
    Rascol O, Brooks DJ, Melamed E, Oertel W, Poewe W, Stocchi F, et al. Rasagiline as an adjunct to levodopa in patients with Parkinson’s disease and motor fluctuations: a randomised, double-blind, parallel-group trial. Lancet 2005;365:947–54.PubMedCrossRefGoogle Scholar
  45. 45.
    Decramer M, Rutten-van Molken M, Dekhuijzen PN, Troosters T, van Herwaarden C, Pellegrino R, et al. Effects of N-acetylcysteine on outcomes in chronic obstructive pulmonary disease: a randomised placebo-controlled trial. Lancet 2005;365:1552–60.PubMedCrossRefGoogle Scholar
  46. 46.
    Grant AM, Avenell A, Campbell MK, McDonald AM, MacLennan GS, McPherson GC, et al. Oral vitamin D3 and calcium for secondary prevention of low-trauma fractures in elderly people: a randomised placebo-controlled trial. Lancet 2005;365:1621–8.PubMedCrossRefGoogle Scholar
  47. 47.
    Marson A, Jacoby A, Johnson A, Kim L, Gamble C, Chadwick D. Immediate versus deferred antiepileptic drug treatment for early epilepsy and single seizures: a randomised controlled trial. Lancet 2005;365:2007–13.PubMedCrossRefGoogle Scholar
  48. 48.
    Kaiser C, Brunner-La Rocca HP, Buser PT, Bonetti PO, Osswald S, Linka A, et al. Incremental cost-effectiveness of drug-eluting stents compared with a third-generation bare-metal stent in a real-world setting: randomised Basel Stent Kosten Effektivitats Trial. Lancet 2005;366:921–9.PubMedCrossRefGoogle Scholar
  49. 49.
    Thatcher N, Chang A, Parikh P, Rodrigues Pereira J, Ciuleanu T, von Pawel J, et al. Gefitinib plus best supportive care in previously treated patients with refractory advanced non-small-cell lung cancer: results from a randomised, placebo-controlled, multicentre study. Lancet 2005;366:1527–37.PubMedCrossRefGoogle Scholar
  50. 50.
    Nitz UA, Mohrmann S, Fischer J, Lindemann W, Berdel WE, Jackisch C, et al. Comparison of rapidly cycled tandem high-dose chemotherapy plus peripheral-blood stem-cell support versus dose-dense conventional chemotherapy for adjuvant treatment of high-risk breast cancer: results of a multicentre phase III trial. Lancet 2005;366:1935–44.PubMedCrossRefGoogle Scholar
  51. 51.
    Wazni OM, Marrouche NF, Martin DO, Verma A, Bhargava M, Saliba W, et al. Radiofrequency ablation vs antiarrhythmic drugs as first-line treatment of symptomatic atrial fibrillation: a randomized trial. JAMA 2005;293:2634–40.PubMedCrossRefGoogle Scholar
  52. 52.
    Ockene JK, Barad DH, Cochrane BB, Larson JC, Gass M, Wassertheil-Smoller S, et al. Symptom experience after discontinuing use of estrogen plus progestin. JAMA 2005;294:183–93.PubMedCrossRefGoogle Scholar
  53. 53.
    Avenell A, Campbell MK, Cook JA, Hannaford PC, Kilonzo MM, McNeil G, et al. Effect of multivitamin and mineral supplements on morbidity from infections in older people: pragmatic, randomised, double blind, placebo controlled trial. BMJ 2005;331:324–7.PubMedCrossRefGoogle Scholar
  54. 54.
    Porthouse J, Cockayne S, King C, Saxon L, Steele E, Aspray T, et al. Randomised controlled trial of calcium and supplementation with cholecalciferol (vitamin D3) for prevention of fractures in primary care. BMJ 2005;330:1003–6.PubMedCrossRefGoogle Scholar
  55. 55.
    Escobar-Morreale HF, Botella-Carretero JI, Gómez-Bueno M, Galán JM, Barrios V, Sancho J. Thyroid hormona replacement therapy in primary hypothiroidism: a randomized trial comparing L-thyroxine plus liothyronine with L-thyroxine alone. Ann Intern Med 2005;142:412–24.PubMedGoogle Scholar
  56. 56.
    Bezjak A, Winton T, Ding K, Graham B, Seymour L Ayoub J, et al. Quality of life in a trail of adjuvant chemotherapy for early stage completely resected non-small cell lung cancer. Lung Cancer 2003;41(suppl 2):S20.CrossRefGoogle Scholar
  57. 57.
    Abbott J, Hart A. Measuring and reporting quality of life outcomes in clinical trials in cystic fibrosis: a critical review. Health Qual Life Outcomes 2005;3:19.PubMedCrossRefGoogle Scholar
  58. 58.
    Clarke SA, Eiser C. The measurement of health-related quality of life (QOL) in paediatric clinical trials: a systematic review. Health Qual Life Outcomes 2004;2:66.PubMedCrossRefGoogle Scholar
  59. 59.
    Eiser C. Use of quality of life measures in clinical trials. Ambul Pediatr 2004;4(4 Suppl):395–9.PubMedCrossRefGoogle Scholar
  60. 60.
    Kong SX, Gandhi SK. Methodologic assessments of quality of life measures in clinical trials. Ann Pharmacother 1997;31:830–6.PubMedGoogle Scholar
  61. 61.
    Kim J, Morris CB, Schulman KA. The role of the Food and Drug Administration in pharmacoeconomic evaluation during the drug development process. Drug Inf J 2000;34:1207–13.Google Scholar
  62. 62.
    Blazeby JM, Avery K, Sprangers M, Pikhart H, Fayers P, Donovan J. Health-related quality of life measurement in randomized clinical trials in surgical oncology. J Clin Oncol 2006;24:3178–86.PubMedCrossRefGoogle Scholar
  63. 63.
    Phillips GA, Van Brunt DL, Roychowdhury SM, Xu W, Naber D. The relationship between quality of life and clinical efficacy from a randomized trial comparing olanzapine and ziprasidone. J Clin Psychiatry 2006;67:1397–403.PubMedCrossRefGoogle Scholar
  64. 64.
    McGregor M, Caro JJ. QALYs: are they helpful to decision makers? Pharmacoeconomics 2006;24:947–52.PubMedCrossRefGoogle Scholar
  65. 65.
    Vijan S. Should we abandon QALYs as a resource allocation tool?. Pharmacoeconomics 2006;24:953–4.PubMedCrossRefGoogle Scholar
  66. 66.
    Prescrire Editorial Staff. European and French pharmaceutical market assessed by Prescrire in 2005: mainly bogus innovation. Farm Hosp 2006;30:68–70.CrossRefGoogle Scholar
  67. 67.
    Greenberg D, Rosen AB, Olchanski NV, Stone PW, Nadai J, Neumann PJ. Delays in publication of cost utility analyses conducted alongside clinical trials: registry analysis. BMJ 2004;328:1536–7.PubMedCrossRefGoogle Scholar
  68. 68.
    Rivero-Arias O, Campbell H, Gray A, Fairbank J, Frost H, Wilson-MacDonald J. Surgical stabilisation of the spine compared with a programme of intensive rehabilitation for the management of patients with chronic low back pain: cost utility analysis based on a randomised controlled trial. BMJ 2005;330:1239–43.PubMedCrossRefGoogle Scholar
  69. 69.
    Zhu W. Making bootstrap statistical inferences: a tutorial. Res Q Exerc Sport 1997;68:44–55.PubMedGoogle Scholar
  70. 70.
    Salkeld G,Henry D, Hill S, Lang D, Freemantle N, D’Assuncao J. What drives health-care spending priorities? An international survey of health-care professionals. PLoS Med 2007;4:e94.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media B.V. 2007

Authors and Affiliations

  • Ramón San Miguel
    • 1
    Email author
  • Ana María López-González
    • 2
  • Eduardo Sanchez-Iriso
    • 3
  • Javier Mar
    • 4
  • Juan M. Cabasés
    • 3
  1. 1.Pharmacy DepartmentHospital Santa Bárbara - SACYLSoriaSpain
  2. 2.Pharmacy DepartmentHospital Clínico Universitario - SACYLValladolidSpain
  3. 3.Department of EconomicsPublic University of NavarraPamplonaSpain
  4. 4.Clinical Management ServiceHospital Alto DebaMondragonSpain

Personalised recommendations