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

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.

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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.

    PubMed  Article  Google Scholar 

  2. 2.

    Walsh JME, Pignone M. Drug treatment of hyperlipidemia in women. JAMA 2004;291:2243–52.

    PubMed  Article  CAS  Google Scholar 

  3. 3.

    Testa MA, Simonson DC. Current concepts: assessment of quality-of-life outcomes. N Engl J Med 1996;334:835–40.

    Article  CAS  Google 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.

    PubMed  Article  CAS  Google 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.

    PubMed  Article  Google 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.

    PubMed  CAS  Google 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.

    PubMed  Article  CAS  Google 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.

    PubMed  CAS  Google 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.

    PubMed  Article  Google 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.

    PubMed  Article  CAS  Google Scholar 

  14. 14.

    Jones PW. St. George’s respiratory questionnaire: MCID. COPD 2005;2:75–9.

    PubMed  Article  Google 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.

    PubMed  Article  CAS  Google 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.

    PubMed  Article  CAS  Google 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.

    PubMed  Article  CAS  Google Scholar 

  18. 18.

    Mahoney FI, Barthel DW. Functional evaluation: the Barthel index. Md Med J 1965;14:61–5.

    CAS  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.

    PubMed  Article  CAS  Google 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.

  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.

    PubMed  Article  CAS  Google 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.

    PubMed  Article  CAS  Google Scholar 

  25. 25.

    Sackett DL, Straus SE, Richardson WS, Rosenber W, Haynes RB. Medicina basada en la evidencia [Evidence-Based Medicine]. Hardcourt: Madrid; 2001.

  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.

    Article  Google 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.

    PubMed  Article  CAS  Google 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.

    PubMed  Article  CAS  Google 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.

    PubMed  Article  CAS  Google 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.

    PubMed  Article  CAS  Google 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.

    PubMed  Article  CAS  Google 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.

    PubMed  Article  CAS  Google 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.

    PubMed  Article  CAS  Google 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.

    PubMed  Article  CAS  Google 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.

    PubMed  Article  CAS  Google 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.

    PubMed  Article  CAS  Google 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.

    PubMed  Article  CAS  Google 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.

    PubMed  Article  CAS  Google 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.

    Article  CAS  Google 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.

    PubMed  Article  CAS  Google 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.

    PubMed  Article  CAS  Google 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.

    PubMed  Article  CAS  Google 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.

    PubMed  Article  CAS  Google 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.

    PubMed  Article  CAS  Google 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.

    PubMed  Article  CAS  Google 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.

    PubMed  Article  CAS  Google 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.

    PubMed  Article  CAS  Google 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.

    PubMed  Article  CAS  Google 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.

    PubMed  Article  CAS  Google 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.

    PubMed  Article  CAS  Google 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.

    PubMed  Article  CAS  Google 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.

    PubMed  Article  CAS  Google 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.

    PubMed  Article  CAS  Google 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.

    PubMed  CAS  Google 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.

    Article  Google 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.

    PubMed  Article  Google 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.

    PubMed  Article  Google Scholar 

  59. 59.

    Eiser C. Use of quality of life measures in clinical trials. Ambul Pediatr 2004;4(4 Suppl):395–9.

    PubMed  Article  Google Scholar 

  60. 60.

    Kong SX, Gandhi SK. Methodologic assessments of quality of life measures in clinical trials. Ann Pharmacother 1997;31:830–6.

    PubMed  CAS  Google 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.

    PubMed  Article  Google 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.

    PubMed  Article  Google Scholar 

  64. 64.

    McGregor M, Caro JJ. QALYs: are they helpful to decision makers? Pharmacoeconomics 2006;24:947–52.

    PubMed  Article  Google Scholar 

  65. 65.

    Vijan S. Should we abandon QALYs as a resource allocation tool?. Pharmacoeconomics 2006;24:953–4.

    PubMed  Article  Google 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.

    Article  Google 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.

    PubMed  Article  Google 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.

    PubMed  Article  Google Scholar 

  69. 69.

    Zhu W. Making bootstrap statistical inferences: a tutorial. Res Q Exerc Sport 1997;68:44–55.

    PubMed  CAS  Google 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.

    PubMed  Article  Google Scholar 

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Acknowledgements

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

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Correspondence to Ramón San Miguel.

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Miguel, R.S., López-González, A.M., Sanchez-Iriso, E. et al. Measuring health-related quality of life in drug clinical trials: is it given due importance?. Pharm World Sci 30, 154–160 (2008). https://doi.org/10.1007/s11096-007-9152-9

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Keywords

  • Health related quality of life
  • Quality of life
  • Clinical trial
  • Pharmacoeconomics