Skip to main content

Advertisement

SpringerLink
Log in

AAPS/RAPS/CAPRA collaborative program: Exploring the challenges of drug regulation in a global environment: Clinical concerns

  • Published:
AAPS PharmSci Aims and scope Submit manuscript

Abstract

Globalization of the pharmaceutical industry has led to a need to harmonize the regulatory requirements governing the marketing of medicinal products. To minimize the barriers impeding global drug product registration, the International Conference on the Harmonization of Technical Requirements of Pharmaceuticals for Human Use (ICH) was established in 1990. The ICH has developed a series of guidelines that reflect agreements reached by participating nations on aspects of the chemistry and clinical technical sections that will fulfill the regulatory requirements of these various jurisdications. Nevertheless, there continue to be points of divergent perspectives and barriers that can impede the use of foreign clinical data. Given the importance of these issues, the Regulatory Science (RS) section of the American Association of Pharmaceutical Scientists (AAPS), in conjunction with the Regulatory Affairs Professional Society (RAPS) and the Canadian Association of Professional Regulatory Affairs (CAPRA) cosponsored a public forum on this topic. This manuscript provides a summary of the speaker presentations and audience discussions regarding the design of clinical trials and the extrapolation of results from these trials to support international drug registration.

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

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Guidance for Industry Clinical Development of Steroidal Contraceptives Used by Women. Health Products and Food Branch. Available at: http://www.hc-sc.gc.ca/hpfb-dgpsa/tpd-dpt/steroidal_contraceptives_e.html. Accessed August 2003.

  2. Therapeutic Products Programme policy, Submissions for Topical Non-Steroidal Anti-inflammatory Drugs (Topical NSAID's). Available at: http://www.he-sc.gc.ca/hpfb-dgpsa/tpd-dpt/topnsaid_e.html. Accessed August 2003.

  3. Note for guidance on the clinical investigation of medicinal products in the treatment of asthma. EMEA, CPMP. Available at: http://www.emea.eu.int/pdfs/human/ewp/29220len.pdf.Accessed August 2003.

  4. Points to consider on clinical investigation of medicinal products for acute stroke. EMEA, CPMP. Available at: http://www.emea.eu.int/pdfs/human/ewp/056098en.pdf. Accessed August 2003.

  5. Appendix to the note for guidance on the clinical investigation of medicinal products in the treatment of schizophrenia-methodology of clinical trials concerning the development of depot preparations of approved medicinal products in schizophrenia. EMEA, CPMP. Available at: http://www.emea.eu.int/pdfs/human/ewp/004901en.pdf. Accessed August 2003.

  6. White HD. International differences: selection, noise, or real? Eur Heart J. 2000;21:339–342.

    Article  CAS  PubMed  Google Scholar 

  7. Davis AF, Long RM. Pharmacogenetics research network and knowledge base second scientific meeting. Pharmacogenomics J. 2002;2:293–296.

    Article  CAS  PubMed  Google Scholar 

  8. Evans WE, Relling MV. Pharmacogenomics: translating functional genomics into rational therapeutics. Science. 1999;286:487–491.

    Article  CAS  PubMed  Google Scholar 

  9. ICH Topic E10: Choice of Control Group in Clinical Trials dated 27 July 2000. Available at: http://www.ich.org/ich5e.html. Accessed August 2003.

  10. Berkowitz SD, Granger CB, Pieper KS, et al. Incidence and predictors of bleeding after thrombolytic therapy for myocardial infarction. Circulation. 1997;95:2508–2516.

    Article  CAS  PubMed  Google Scholar 

  11. Graf J, Doig GS, Cook DJ, Vincent JL, Sibbald WJ. Randomized, controlled clinical trials in sepsis: has methodological quality improved over time? Crit Care Med. 2002;30:461–472.

    Article  PubMed  Google Scholar 

  12. Medical Dictionary for Regulatory Activities. Available at: http://www.meddramsso.com/new webaug 2001/meddramsso/med dra/index.htm. Accessed August 2003.

  13. Labs KH, Dormandy JA, Jaeger KA, Stuerzebecher CS, Hiatt WR. Transatlantic conference on clinical trial guidelines in PAOD (peripheral arterial occlusive disease) clinical trial methodology. Eur J Vasc Endovasc Surg. 1999;18:253–265.

    Article  CAS  PubMed  Google Scholar 

  14. Ono S, Kodama Y, Nagao T, Toyoshima S. The quality of conduct in Japanese clinical trials: deficiencies found in GCP inspections. Control Clin Trials. 2002;23:29–41.

    Article  PubMed  Google Scholar 

  15. Patriarca PA, Wright PF, John TJ. Factors affecting the immunogenicity of oral poliovirus vaccine in developing countries: review. Rev Infect Dis. 1991;13:926–939.

    Article  CAS  PubMed  Google Scholar 

  16. O'Shea JC, Califf RM. International differences in cardiovascular clinical trials. Am Heart J. 2001;141:866–874.

    Article  PubMed  Google Scholar 

  17. O'Shea JC, Califf RM. International differences in treatment effects in cardiovascular clinical trials. Am Heart J. 2001;141:875–880.

    Article  PubMed  Google Scholar 

  18. O'Shea JC, DeMets DL. Statistical issues relating to international differences in clinical trials. Am Heart J. 2001;142:21–28.

    Article  PubMed  Google Scholar 

  19. Akkerhuis KM, Deckers JW, Boersma E, et al. Geographic variability in outcomes within an international trial of glycoprotein IIb/IIIa inhibition in patients with acute coronary syndromes. Results from PURSUIT. Eur Heart J. 2000;21:371–381.

    Article  CAS  PubMed  Google Scholar 

  20. Shapito ED. Protective efficacy trials. In: Ellis RW, Granoff DM, eds. Development and Clinical Uses of Haemophilus b Conjugate Vaccines. New York, NY: Marcel Dekker; 1994:339–356.

    Google Scholar 

  21. Points to consider on switching between superiority and noninferiority, EMEA, CPMP. Available at: http://www.emea.eu.int/pdfs/human/ewp/048299en.pdf. Accessed August 2003

  22. Khan A, Khan S, Brown WA. Are placebo controls necessary to test new antidepressants and anxiolytics? Int J Neuropsychopharmacol. 2002;5:193–197.

    Article  CAS  PubMed  Google Scholar 

  23. Hypericum Depression Trial Study Group. Effect of Hypericum perforatum (St John's wort) in major depressive disorder: a randomized controlled trial. JAMA. 2002;287:1807–1814.

    Article  Google Scholar 

  24. Simon RM, Steinberg SM, Hamilton M, et al. Clinical trial designs for the early clinical development of therapeutic vaccines. J Clin Oncol. 2001;19:1848–1854.

    CAS  PubMed  Google Scholar 

  25. Haffner ME. Designing clinical trials to study rare disease treatment. Drug Inf J. 1998;32:957–960.

    Google Scholar 

  26. Evans WE, Relling MV. Pharmacogenomics: translating functional genomics into rational therapeutics. Science. 1999;286:487–491.

    Article  CAS  PubMed  Google Scholar 

  27. Meisel C, Gerloff T, Kirchheiner J, et al. Implications of pharmacogenetics for individualizing drug treatment and for study design. J Mol Med. 2001;81:154–167.

    Google Scholar 

  28. Nebert DW. Pharmacogenetics and pharmacogenomics: why is this relevant to the clinical geneticist? Clin Genet. 1999;56:247–258.

    Article  CAS  PubMed  Google Scholar 

  29. Carson PE, Flanagan CL, Ickes CE, Alvong AS. Enzymatic deficiency in primaquine sensitive erythrocytes. Science. 1956;124:484–485.

    Article  CAS  PubMed  Google Scholar 

  30. ICH Harmonised tripartite guideline: Ethnic factors in the acceptability of foreign clinical data. International Conference on Harmonisation of technical requirements for registration of pharmaceuticals for human use, 5 February 1998. Available at: http://www.ich.org/pdfICH/e5.pdf. Accessed August 2003.

  31. Davis AF, Long RM. Pharmacogenetics research network and knowledge base second scientific meeting. Pharmacogenomics J. 2002;2(5):293–296.

    Article  CAS  PubMed  Google Scholar 

  32. Drazen JM, Yandava CN, Dube L, et al. Pharmacogenetic association between ALOX5 promoter genotype and the response to anti-asthma treatment. Nat Genet. 1999;22:168–170.

    Article  CAS  PubMed  Google Scholar 

  33. Palmer LJ, Silverman ES, Weiss ST, Drazen JM. Pharmacogenetics of asthma. Am J Respir Crit Care Med. 2002;165:861–866.

    Article  PubMed  Google Scholar 

  34. Kottakis J, Wood R, Le Gros V, Della Cioppa G. Clinical efficacy with formoterol in the absence of a response to salmeterol: a review. Int J Clin Pract. 2001;55:476–479.

    CAS  PubMed  Google Scholar 

  35. Rutledge DR. Race and hypertension. What is clinically relevant? Drugs. 1994;47:914–932.

    Article  CAS  PubMed  Google Scholar 

  36. Saunders E. Tailoring treatment to minority patients. Am J Med. 1990;88:21S-23S.

    Article  CAS  PubMed  Google Scholar 

  37. Lau EMC, Lee JK, Suriwongpaisal P, et al. The incidence of hip fracture in four Asian countries: the Asian osteoporosis study (AOS). Osteoporos Int. 2001;12:239–243.

    Article  CAS  PubMed  Google Scholar 

  38. Ross PD, Huang C. Hip fracture incidence among Caucasians in Hawaii is similar to Japanese. A population-based study. Aging (Milano). 2000;12:356–359.

    CAS  Google Scholar 

  39. Cummings SR, Cauley JA, Palermo L, et al. Racial differences in hip axis lengths might explain racial differences in rates of hip fracture. Study of Osteoporotic Fractures Research Group. Osteoporos Int. 1994;4:226–229.

    Article  CAS  PubMed  Google Scholar 

  40. Glasel JA. Drugs, the human genome, and individual-based medicine. Prog Drug Res. 2002;58:1–50.

    Article  CAS  PubMed  Google Scholar 

  41. Al Suwaidi J, Salam AM. Platelet glycoprotein IIb/IIIa receptor blockade in coronary artery disease. Curr Control Trials Cardiovasc Med. 2001;2:171–179.

    Article  PubMed  PubMed Central  Google Scholar 

  42. Cheng JW. Efficacy of glycoprotein IIb/IIIa-receptor inhibitors during percutaneous coronary intervention. Am J Health Syst Pharm. 2002;59(suppl 7):S5-S14.

    CAS  PubMed  Google Scholar 

  43. Schwartz LM, Fisher ES, Tosteson NA, et al. Treatment and health outcomes of women and men in a cohort with coronary artery disease. Arch Intern Med. 1997;157:1545–1551.

    Article  CAS  PubMed  Google Scholar 

  44. Talley NJ, Stanghellini V, Heading R, Koch KL, Malagelada JR, Tytgat GNJ. Functional gastroduodenal disorders. Gut. 1999;45(suppl 2):I37-I42.

    Google Scholar 

  45. American Gastroenterological Association (AGA) Clinical Practice and Practice Economics Committe. American Gastroen-terological Association medical position statement: evaluation of dyspepsia. Gastroenterology, 1998;114:579–581.

    Article  Google Scholar 

  46. Veldhuyzen van Zanten SJ, Flook N, Chiba N, et al. An evidence-based approach to the management of uninvestigated dyspepsia in the era of Helicobacter pylori. Canadian Dyspepsia Working Group. CMAJ. 2000;162(suppl):S3–23.

    Google Scholar 

  47. Mark DB, Naylor CD, Hlatky MA, et al. Use of medical resources and quality of life after acute myocardial infaction in Canada and the United States. N Engl J Med. 1994;331:1130–1135.

    Article  CAS  PubMed  Google Scholar 

  48. Rouleau JL, Moye LA, Pfeffer MA, et al. A comparison of management patterns after acute myocardial infarction in Canada and the United States. N Engl J Med. 1993;328:779–784.

    Article  CAS  PubMed  Google Scholar 

  49. Glick HA, Polsky D, Willke RJ, Alves WM, Kassel N, Schulman K. Comparison of the use of medical resources and outcomes in the treatment of aneurysmal subarachnoid hemorrhage between Canada and the US. Stroke. 1998;29:351–358.

    Article  CAS  PubMed  Google Scholar 

  50. Fu Y, Chang WC, Mark D, et al. Canadian-American differences in the management of acute coronary syndromes in the GUSTO IIb trial: one-year follow-up of patients without ST-segment elevation. Circulation. 2000;102:1375–1381.

    Article  CAS  PubMed  Google Scholar 

  51. Haraoui B, for the Subcommittee on Biologic Agents, Canadian Rheumatology Association. Position on the use of biologic agents for the treatment of rheumatoid arthritis. Available at: http://www.cra.ucalgary.ca/cral/announcements/CRA FinalPositionStatement.pdf. Accessed August 2003.

  52. Ontario Drug Benefit Formulary. Available at: http://www.health.gov.on.ca/english/providers/program/drugs/odb_f_mn.html. Accessed August 2003.

  53. Lewis SJ. Further disquiet on the guidelines front. CMAJ. 2001;165:180–181.

    CAS  PubMed  PubMed Central  Google Scholar 

  54. Canadian Medical Association Infobase: clinical practice guidelines. Available at: http://mdm.ca/cpgsnew/cpgs/index.asp. Accessed August 2003.

  55. Graham ID, Beardall S, Carter AO, et al. What is the quality of drug therapy clinical practice guidelines in Canada. CMAJ. 2001;165:157–163.

    CAS  PubMed  PubMed Central  Google Scholar 

  56. Hunt RH, Thomson ABR. Canadian Helicobacter pylori Consensus Conference. Can J Gastroenterol. 1998;12:31–41.

    CAS  PubMed  Google Scholar 

  57. Hunt RH, Fallone CA, Thomson ABR, for the Canadian Helicobacter Study Group. Canadian Helicobacter pylori consensus Conference update: infection in adults. Can J Gastroenterol. 1999;13:213–217.

    CAS  PubMed  Google Scholar 

  58. Thomson AB, for the Canadian Helicobacter Study Group. Risks and benefits of Helicobacter pylori eradication: current status. Can J Gastroenterol. 2002;16:57–62.

    PubMed  Google Scholar 

  59. Veldhuyzen van Zanten SJ, Sherman PM, Hunt RH, Helicobacter pylori: new developments and treatments, CMAJ. 1997;156:1565–1574.

    CAS  PubMed  PubMed Central  Google Scholar 

  60. Peterson WL, Graham DY, Marshall B, et al. Clarithromycin as monotherapy for eradication of Helicobacter pylori: a randomized, double-blind trial. Am J Gastroenterol. 1993;88:1860–1864.

    CAS  PubMed  Google Scholar 

  61. Lind T, Veldhuyzen van Zanten SJ, Unge P, et al. Eradication of Helicobacter pylori using one-week triple therapies combining omeprazole with two antimicrobials: the MACH I Study. Helicobacter. 1996;1:138–144.

    Article  CAS  PubMed  Google Scholar 

  62. ICH Harmonised tripartite guideline: Preclinical safety evaluation of biotechnology-derived pharmaceuticals. International Conference on Harmonisation of technical requirements for registration of pharmaceuticals for human use, 16 July 1997. Available at: http://www.ich.org/pdfICH/s6.pdf.Accessed August 2003.

  63. Kirby JT, Mutnick AH, Jones RN, Biedenbach DJ, Pfaller MA. Geographic variations in garenoxacin (BMS284756) activity tested against pathogens associated with skin and soft tissue infections: report from the SENTRY Antimicrobial Surveillance Program (2000). Diagn Microbiol Infect Dis. 2002;43:303–309.

    Article  CAS  PubMed  Google Scholar 

  64. Diekema DJ, Pfaller MA, Schmitz FJ, et al. Survey of infections due to Staphylococcus species: frequency of occurrence and antimicrobial susceptibility of isolates collected in the United States, Canada, Latin America, Europe, and the Western Pacific region for the SENTRY Antimicrobial Surveillance Program, 1997–1999. Clin Infect Dis. 2001;32(suppl 2):S114-S132.

    Article  CAS  PubMed  Google Scholar 

  65. Gales AC, Jones RN, Turnidge J, Rennie R, Ramphal R. Characterization of Pseudomonas aeruginosa isolates: occurrence rates, antimicrobial susceptibility patterns, and molecular typing in the global SENTRY antimicrobials surveillance program, 1997–1999 Clin Infect Dis. 2001;32(suppl 2):S146-S155.

    Article  CAS  PubMed  Google Scholar 

  66. Pfaller MA, Diekema DJ, Jones RN, et al. International surveillance of blood infections due to Candida species: frequency of occurrence and in vitro susceptibilities to fluconazole, ravuconazole, and voriconazole of isolates collected from 1997 through 1999 in the SENTRY antimicrobial surveillance program. J Clin Microbiol. 2001;39:3254–3259.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Meis J, Petron M, Bille J, Ellis D, Gibbs D. A global evaluation of the susceptibility of Candida species to fluconazole by disk diffusion. Diagn Microbiol Infect Dis. 2000;36:215–223.

    Article  CAS  PubMed  Google Scholar 

  68. Liebowitz LD, Ashbee HR, Evan EGV, et al. A two-year global evaluation of the susceptibility of Canadida species to fluconazole by disk diffusion. Diagn Microbiol Infect Dis. 2001;40:27–33.

    Article  CAS  PubMed  Google Scholar 

  69. Winokur PL, Canton R, Casellas J-M, Legakis N. Variations in the prevalence of strains expressing an extended-spectrum β-lactamase phenotype and characterization of isolates from Europe, the Americas, and the Western Pacific region. Clin Infect Dis. 2001;32(suppl 2):S94-S103.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Center for Veterinary Medicine, Food and Drug Administration, 20855, Rockville, MD

    Marilyn N. Martinez

  2. McGilveray Pharmacon Inc, Ontario, Canada

    Iain McGilveray

Authors
  1. Marilyn N. Martinez
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Iain McGilveray
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Marilyn N. Martinez.

Additional information

Published: October 23, 2003

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Martinez, M.N., McGilveray, I. AAPS/RAPS/CAPRA collaborative program: Exploring the challenges of drug regulation in a global environment: Clinical concerns. AAPS PharmSci 5, 27 (2003). https://doi.org/10.1208/ps050427

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1208/ps050427

Keywords

Search

Navigation