Skip to main content
SpringerLink
Log in

Study Design and Endpoints

  • Chapter
Clinical Trials in Osteoporosis

Part of the book series: Clinical Trials ((CLINICAL))

  • 755 Accesses

Abstract

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 is inadequate, 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 metaanalysis. It is important to get the design right from the start. The time taken will be very worthwhile. The purpose of this chapter is to give an overview of the following:

  1. 1.

    Phase I to IV studies and different trial types

  2. 2.

    Endpoints

  3. 3.

    Study design, size, and power

  4. 4.

    The effect of antiresorptive therapies versus true anabolic therapies on trial design

  5. 5.

    Inclusion and exclusion criteria

  6. 6.

    Study protocols and documentation

  7. 7.

    Sampling and randomization

  8. 8.

    Design of data collection.

The chapter will also discuss the advantages of true clinical and health-status outcomes compared with the more common use of surrogate outcomes.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 84.99
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 109.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. FDA Guidelines for the Preclinical and Clinical Evaluation of Agents used in the Prevention or Treatment of Postmenopausal Osteoporosis (1994). http://www.fda.gov/cder/guidance/osteo.pdf accessed 13/11/06

    Google Scholar 

  2. Deeks, J., Glanville, J. and Sheldon, T. (1996). Undertaking Systematic Reviews of Research on Effectiveness. CRD Report 4, NHS Centre for Reviews and Dissemination. York: University of York.

    Google Scholar 

  3. Liberman, U.A., Weiss, S.R., Broll, J. et al. (1995). Effect of oral alendronate on bone mineral density and the incidence of fractures in postmenopausal osteoporosis. N Engl J Med 333:1437–43.

    Article  PubMed  CAS  Google Scholar 

  4. Sahota, O., San, P., Cawte, S.A. et al. (2000). 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 11:52–8.

    Article  PubMed  CAS  Google Scholar 

  5. Cranney, A., Tugwell, P., Cummings, S. et al. (1997). Osteoporosis Clinical Trial Endpoints: Candidate Variables and Clinimetric Properties. J Rheumatol 24:1222–9.

    PubMed  CAS  Google Scholar 

  6. Notes for Guidance on Postmenopausal Osteoporosis in Women. Committee for Proprietary Medicinal Products (CPMP), 2001. http://www.emea.eu.int/pdfs/human/ewp/055295en.pdf accessed 13/11/06

    Google Scholar 

  7. Eastell, R., Cedel, S., Wahner, H.W. et al. (1991). Classification of vertebral fractures. J Bone Miner Res 6:207–15.

    Article  PubMed  CAS  Google Scholar 

  8. Black, D.M., Cummings, S.R., Stone, K. et al. (1991). A new approach to defining normal vertebral dimensions. J Bone Miner Res 6:883–92.

    PubMed  CAS  Google Scholar 

  9. McCloskey, E.V., Spector, T.D., Eyres, K.S. et al. (1993). The assessment of vertebral deformity: A method for use in population studies and clinical trials. Osteoporos Int 3:138–47.

    Article  PubMed  CAS  Google Scholar 

  10. Cook, D.J., Guyatt, G.H., Adachi, J.D. et al. (1999). 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 10:207–13.

    Article  PubMed  CAS  Google Scholar 

  11. Randell, A.G., Bhalerao, N., Nguyen, T.V. et al. (1998). Quality of life in osteoporosis: reliability, consistency, and validity of the Osteoporosis Assessment Questionnaire. J Rheumatol 25:1171–9.

    PubMed  CAS  Google Scholar 

  12. Helmes, E., Hodsman, A., Lazowski, D. et al. (1995). A questionnaire to evaluate disability in osteoporotic patients with vertebral compression fractures. J Gerontol A Biol Sci Med Sci 50:M91–8.

    PubMed  CAS  Google Scholar 

  13. Lips, P., Cooper, C., Agnusdei, D. et al. (1999). 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 10:150–60.

    Article  PubMed  CAS  Google Scholar 

  14. Ware, J.E., Jr and Gandek, B. (1998). Overview of the SF-36 Health Survey and the International Quality of Life Assessment (IQOLA) Project. J Clin Epidemiol 51:903–12.

    Article  PubMed  Google Scholar 

  15. Hurst, N.P., Kind, P., Ruta, D. et al. (1997). Measuring health-related quality of life in rheumatoid arthritis: validity, responsiveness and reliability of EuroQol (EQ-5D). Br J Rheumatol 36:551–9.

    Article  PubMed  CAS  Google Scholar 

  16. Tilyard, M.W., Spears, G.F., Thomson, J. et al. (1992). Treatment of postmenopausal osteoporosis with calcitriol or calcium. N Engl J Med 326:357–62.

    Article  PubMed  CAS  Google Scholar 

  17. Pocock, S.J. (1983). Clinical Trials: A Practical Approach. Chichester: John Wiley & Sons.

    Google Scholar 

  18. Reginster, J.Y., Deroisy, R., Lecart, M.P. et al. (1995). A double-blind, placebocontrolled, dose-finding trial of intermittent nasal salmon calcitonin for prevention of postmenopausal lumbar spine bone loss. Am J Med 98:452–8.

    Article  PubMed  CAS  Google Scholar 

  19. Cranney, A., Tugwell, P., Zytaruk, N. et al. (2002). Meta-analyses of therapies for postmenopausal osteoporosis. VI. Meta-analysis of calcitonin for the treatment of postmenopausal osteoporosis. Endocr Rev 23:540–51.

    Article  PubMed  CAS  Google Scholar 

  20. Hubbard, W.K. (1998). International Conference on Harmonization: Guidance on Statistical Principles for Clinical Trials. Federal Register 63:49583–98 http://www.fda.gov/cder/guidance/91698.pdf accessed 13/11/06

    Google Scholar 

  21. Kim, J.S. (1997). Determining Sample Size for Testing Equivalence. MDDI May:114–17 http://www.devicelink.com/mddi/archive/97/05/020.html accessed 13/11/06

    Google Scholar 

  22. Ettinger, B., Pressman, A. and Silver, P. (1999). Effect of age on reasons for initiation and discontinuation of hormone replacement therapy. Menopause 6:282–9.

    Article  PubMed  CAS  Google Scholar 

  23. Faulkner, D.L., Young, C., Hutchins, D. et al. (1998). Patient noncompliance with hormone replacement therapy: a nationwide estimate using a large prescription claims database. Menopause 5:226–9.

    PubMed  CAS  Google Scholar 

  24. Vestergaard, P., Hermann, A.P., Gram, J. et al. (1997). Improving compliance with hormonal replacement therapy in primary osteoporosis prevention. Maturitas 28:137–45.

    Article  PubMed  CAS  Google Scholar 

  25. Cummings, S.R., Black, D.M., Thompson, D.E. et al. (1998). Effect of alendronate on risk of fracture in women with low bone density but without vertebral fractures: results from the Fracture Intervention Trial. JAMA 280:2077–82.

    Article  PubMed  CAS  Google Scholar 

  26. Cole, R.P., Palushock, S. and Haboubi, A. (1999). Osteoporosis management: physicians’ recommendations and women’s compliance following osteoporosis testing. Women Health 29:101–15.

    Article  PubMed  CAS  Google Scholar 

  27. Kurland, E.S., Cosman, F., McMahon, D.J. et al. (2000). Parathyroid hormone as a therapy for idiopathic osteoporosis in men: effects on bone mineral density and bone markers. J Clin Endocrinol Metab 85:3069–76.

    Article  PubMed  CAS  Google Scholar 

  28. Stewart, A.F., Cain, R.L., Burr, D.B. et al. (2000). 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 15:1517–25.

    Article  PubMed  CAS  Google Scholar 

  29. Hodsman, A.B., Kisiel, M., Adachi, J.D. et al. (2000). 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 27:311–18.

    Article  PubMed  CAS  Google Scholar 

  30. Altman, D.G. (1996). Better reporting of randomised controlled trials: the CONSORT statement. BMJ 313:570–1.

    PubMed  CAS  Google Scholar 

  31. ICH Harmonized Tripartite Guideline E6 Good Clinical Practice: Consolidated Guidance. http://www.fda.gov/cder/guidance/959fnl.pdf accessed 13/11/06

    Google Scholar 

  32. Rice, P.L. and Ezzy, D. (1999). Qualitative Research Methods: A Health Focus. Oxford: Oxford University Press.

    Google Scholar 

  33. Holloway, W. and Jefferson, T. (2000). Doing Qualitative Research Differently. London: Sage Publications.

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Medical Physics and Clinical Engineering, Nottingham University Hospitals NHS Trust, Nottingham, UK

    Dr Derek Pearson

  2. Medical Affairs, Bio-Imaging Technologies Inc., Newtown, PA, USA

    Dr Colin G. Miller (Senior Vice President)

Authors
  1. Dr Derek Pearson
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Dr Colin G. Miller
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Medical Physics & Clinical Engineering Department, Nottingham University Hospitals NHS Trust, Nottingham, UK

    Derek Pearson BSc, PhD (Joint Service Manager) (Joint Service Manager)

  2. Medical Affairs, Bio-Imaging Technologies Inc., Newtown, PA, USA

    Colin G. Miller PhD, FICR (Sr. Vice President) (Sr. Vice President)

Rights and permissions

Reprints and permissions

Copyright information

© 2007 Springer-Verlag London Limited

About this chapter

Cite this chapter

Pearson, D., Miller, C.G. (2007). Study Design and Endpoints. In: Pearson, D., Miller, C.G. (eds) Clinical Trials in Osteoporosis. Clinical Trials. Springer, London. https://doi.org/10.1007/978-1-84628-587-5_2

Download citation

  • DOI: https://doi.org/10.1007/978-1-84628-587-5_2

  • Publisher Name: Springer, London

  • Print ISBN: 978-1-84628-389-5

  • Online ISBN: 978-1-84628-587-5

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation