Study Design and Endpoints

  • Derek Pearson
  • Colin G. Miller


It is the design of your study that will give it credence in the wider scientific community. If it is clear from the dissemination of the study that there has not been a clear hypothesis, endpoints are inappropriate and the study design inadequate, then it is unlikely that the outcome of the study will be used to contribute to the process of regulatory approval, or form part of a meta-analysis. It is important to get the design right from the start. The time taken will be well worth it.


Vertebral Fracture Postmenopausal Osteoporosis Regulatory Approval Equivalence Trial Broadband Ultrasound Attenuation 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Guidelines for the Preclinical and Clinical Evaluation of Agents used in the Prevention or Treatment of Postmenopausal Osteoporosis. FDA, 1994 (
  2. 2.
    Deeks J, Glanville J, Sheldon T. Undertaking Systematic Reviews of Research on Effectiveness. CRD Report 4, NHS Centre for Reviews and Dissemination, University of York, 1996.Google Scholar
  3. 3.
    Liberman UA, Weiss SR, Broil J et al. Effect of oral alendronate on bone mineral density and the incidence of fractures in postmenopausal osteoporosis. N Engl J Med 1995; 333: 1437–43.PubMedCrossRefGoogle Scholar
  4. 4.
    Sahota O, San P, Cawte SA, Pearson D, Hosking DJ. A comparison of the longitudinal changes in quantitative ultrasound with dual-energy X-ray absorptiometry: the four-year effects of hormone replacement therapy. Osteoporos Int 2000; 11: 52–8.PubMedCrossRefGoogle Scholar
  5. 5.
    Cranney A, Tugwell P, Cummings S et al. Osteoporosis Clinical Trial Endpoints: Candidate Variables and Clinimetric Properties. J Rheumatol 1997; 24: 1222–9.PubMedGoogle Scholar
  6. 6.
    Notes for Guidance on Postmenopausal Osteoporosis in Women. Committee for Proprietary Medicinal Products (CPMP), 2001 (
  7. 7.
    Eastell R, Cedel S, Wahner HW, Riggs BL, Melton LJ. Classification of vertebral fractures. J Bone Miner Res 1991; 6: 207–15.PubMedCrossRefGoogle Scholar
  8. 8.
    Black DM, Cummings SR, Stone K, Hudes E, Palermo L, Steiger P. A new approach to defining normal vertebral dimensions. J Bone Miner Res 1991; 6: 883–92.PubMedCrossRefGoogle Scholar
  9. 9.
    McCloskey EV, Spector TD, Eyres KS et al. The assessment of vertebral deformity: A method for use in population studies and clinical trials. Osteoporos Int 1993; 3: 138–47.PubMedCrossRefGoogle Scholar
  10. 10.
    Cook DJ, Guyatt GH, Adachi JD et al. Development and validation of the mini-osteoporosis quality of life questionnaire (OQLQ) in osteoporotic women with back pain due to vertebral fractures. Osteoporosis Quality of Life Study Group. Osteoporos Int 1999; 10: 207–13.PubMedCrossRefGoogle Scholar
  11. 11.
    Randell AG, Bhalerao N, Nguyen TV et al. Quality of life in osteoporosis: reliability, consistency, and validity of the Osteoporosis Assessment Questionnaire. J Rheumatol 1998; 25: 1171–9.PubMedGoogle Scholar
  12. 12.
    Helmes E, Hodsman A, Lazowski D et al. A questionnaire to evaluate disability in osteoporotic patients with vertebral compression fractures. J Gerontol A Biol Sci Med Sci 1995; 50: M91–8.PubMedCrossRefGoogle Scholar
  13. 13.
    Lips P, Cooper C, Agnusdei D et al. Quality of life in patients with vertebral fractures: validation of the Quality of Life Questionnaire of the European Foundation for Osteoporosis (QUALEFFO). Working Party for Quality of Life of the European Foundation for Osteoporosis. Osteoporos Int 1999; 10: 150–60.PubMedCrossRefGoogle Scholar
  14. 14.
    Ware JE Jr, Gandek B. Overview of the SF-36 Health Survey and the International Quality of Life Assessment (IQOLA) Project. J Clin Epidemiol 1998; 51: 903–12.PubMedCrossRefGoogle Scholar
  15. 15.
    Hurst NP, Kind P, Ruta D, Hunter M, Stubbings A. Measuring health-related quality of life in rheumatoid arthritis: validity, responsiveness and reliability of EuroQol (EQ-5D). Br J Rheumatol 1997; 36: 551–9.PubMedCrossRefGoogle Scholar
  16. 16.
    Tilyard MW, Spears GF, Thomson J, Dovey S. Treatment of postmenopausal osteoporosis with calcitriol or calcium. N Engl J Med 1992; 326: 357–62.PubMedCrossRefGoogle Scholar
  17. 17.
    Pocock SJ Clinical Trials: A Practical Approach. Chichester: John Wiley & Sons. 1983.Google Scholar
  18. 18.
    International Conference on Harmonization: Guidance on Statistical Principles for Clinical Trials. Federal Register 1998;63:49583–98. (Available at Scholar
  19. 19.
    Kim. JS. Determining Sample Size for Testing Equivalence. Medical Device and Diagnostic Industry. May 1997:114–117. (Available at 020.html)Google Scholar
  20. 20.
    Ettinger B, Pressman A, Silver P. Effect of age on reasons for initiation and discontinuation of hormone replacement therapy. Menopause 1999; 6: 282–9.PubMedCrossRefGoogle Scholar
  21. 21.
    Faulkner DL, Young C, Hutchins D, McCollam JS. Patient noncompliance with hormone replacement therapy: a nationwide estimate using a large prescription claims database. Menopause 1998; 5: 226–9.PubMedGoogle Scholar
  22. 22.
    Vestergaard P, Hermann AP, Gram J et al. Improving compliance with hormonal replacement therapy in primary osteoporosis prevention. Maturitas 1997; 28: 137–45.PubMedCrossRefGoogle Scholar
  23. 23.
    Cummings SR, Black DM, Thompson DE et al. Effect of alendronate on risk of fracture in women with low bone density but without vertebral fractures: results from the Fracture Intervention Trial. JAMA 1998; 280: 2077–82.PubMedCrossRefGoogle Scholar
  24. 24.
    Cole RP, Palushock S, Haboubi A. Osteoporosis management: physicians’ recommendations and women’s compliance following osteoporosis testing. Women Health 1999; 29: 101–15.PubMedCrossRefGoogle Scholar
  25. 25.
    Kurland ES, Cosman F, McMahon DJ, Rosen CJ, Lindsay R, Bilezikian JP. Parathyroid hormone as a therapy for idiopathic osteoporosis in men: effects on bone mineral density and bone markers. J Clin Endocrinol Metab 2000; 85: 3069–76.PubMedCrossRefGoogle Scholar
  26. 26.
    Stewart AF, Cain RL, Burr DB, Jacob D, Turner CH, Hock JM. Six-month daily administration of parathyroid hormone and parathyroid hormone-related protein peptides to adult ovariectomized rats markedly enhances bone mass and biomechanical properties: a comparison of human parathyroid hormone 1–34, parathyroid hormone-related protein 1–36, and SDZ-parathyroid hormone 893. J Bone Miner Res 2000; 15: 1517–25.PubMedCrossRefGoogle Scholar
  27. 27.
    Hodsman AB, Kisiel M, Adachi JD, Fraher LJ, Watson PH. Histomorphometric evidence for increased bone turnover without change in cortical thickness or porosity after 2 years of cyclical hPTH(1–34) therapy in women with severe osteoporosis. Bone 2000; 27: 311–18.PubMedCrossRefGoogle Scholar
  28. 28.
    Altman DG. Better reporting of randomised controlled trials: the CONSORT statement. BMJ 1996; 313: 570–1.PubMedCrossRefGoogle Scholar
  29. 29.
    ICH Harmonized Tripartite Guideline E6 Good Clinical Practice: Consolidated Guidance (
  30. 30.
    Rice PL, Ezzy D. Qualitative Research Methods: A Health Focus. Oxford University Press, 1999.Google Scholar
  31. 31.
    Holloway W, Jefferson T. Doing Qualitative Research Differently. London. Sage Publications, 2000.Google Scholar

Copyright information

© Springer-Verlag London 2002

Authors and Affiliations

  • Derek Pearson
  • Colin G. Miller

There are no affiliations available

Personalised recommendations