A comparison of interventional clinical trials in rare versus non-rare diseases: an analysis of ClinicalTrials.gov

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• 作者：Stuart A Bell (1)
  Catrin Tudur Smith (1)
  
  1. Department of Biostatistics ; University of Liverpool ; Duncan Building ; Daulby Street ; Liverpool ; L69 3GA ; UK
  
• 关键词：Rare disease clinical trial ; ClinicalTrials.gov
• 刊名：Orphanet Journal of Rare Diseases
• 出版年：2014
• 出版时间：December 2014
• 年：2014
• 卷：9
• 期：1
• 全文大小：687 KB
• 参考文献：1. Office of Rare Diseases Research: / Frequently Asked Questions. http://rarediseases.info.nih.gov/about-ordr/pages/31/frequently-asked-questions. (accessed 13 November 2013).
  2. The Council of the European Union: REGULATION (EC) No 141/2000. / Off J Eur Union 2000, L18/1:5.
  3. Orphanet Consortium: / Rare disease search. http://www.orpha.net/consor/cgi-bin/index.php?lng=EN. (accessed 20 June 2013).
  4. Kesselheim, AS, Myers, JA, Avorn, J (2011) Characteristics of clinical trials to support approval of orphan vs nonorphan drugs for cancer. JAMA 305: pp. 2320-2326 CrossRef
  5. Orfali, M, Feldman, L, Bhattacharjee, V, Harkins, P, Kadam, S, Lo, C, Ravi, M, Shringarpure, DT, Mardekian, J, Cassino, C, Cote, T (2012) Raising orphans: how clinical development programs of drugs for rare and common diseases are different. Clin Pharmacol Ther 92: pp. 262-264 CrossRef
  6. Kesselheim AS, Avorn J: Drug labels: a flawed source of data for studying orphan drug approvals. / Clin Pharmacol Ther 2012, 92(6):694. doi:10.1038/clpt.2012.166 [published Online First: 17 October 2012].
  7. Picavet E, Cassiman D, Hollak CE, Maertens JA, Simoens S: Clinical evidence for orphan medicinal products--a cause for concern? / Orphanet J Rare Dis 2013, 8(1):164. doi:10.1186/1750-1172-8-164 [published Online First: 16 October 2013].
  8. Joppi, R, Bertele, V, Garattini, S (2013) Orphan drugs, orphan diseases. The first decade of orphan drug legislation in the EU. Eur J Clin Pharmacol 69: pp. 1009-1024 CrossRef
  9. Ross JS, Mulvey GK, Hines EM, Nissen SE, Krumholz HM: Trial publication after registration in ClinicalTrials.Gov: a cross-sectional analysis. / PLoS Med 2009, 6(9):e1000144. doi:10.1371/journal.pmed.1000144 [published Online First: 8 September 2009].
  10. Subramanian, J, Madadi, AR, Dandona, M, Williams, K, Morgensztern, D, Govindan, R (2010) Review of ongoing clinical trials in Non-small cell lung cancer a status report for 2009 from the ClinicalTrials.gov website. J Thorac Oncol 5: pp. 1116-1119 CrossRef
  11. Tasneem A, Aberle L, Ananth H, Chakraborty S, Chiswell K, McCourt BJ, Pietrobon R: The database for aggregate analysis of ClinicalTrials.gov (AACT) and subsequent regrouping by clinical specialty. / PLoS One 2012, 7(3):e33677. doi: 10.1371/journal.pone.0033677 [published Online First: 16 March 2012].
  12. Califf, RM, Kramer, JM, Tasneem, A, Zarin, DA, Sherman, RE, Aberle, LH (2012) Characteristics of clinical trials registered in clinicaltrials.gov, 2007鈥?010. JAMA 307: pp. 1838-1847 CrossRef
  13. Hirsch, BR, Califf, RM, Cheng, SK, Tasneem, A, Horton, J, Chiswell, K, Schulman, KA, Dilts, DM, Abernethy, AP (2013) Characteristics of oncology clinical trials: insights from a systematic analysis of ClinicalTrials.gov.. JAMA Intern Med 173: pp. 972-979 CrossRef
  14. Clinical Trials Transformation Initiative: / AACT Database. http://www.ctti-clinicaltrials.org/what-we-do/analysis-dissemination/state-clinical-trials/aact-database. (accessed 26 June 2013).
  15. US National Library of Medicine: / Medical subjects heading. http://www.nlm.nih.gov/mesh/obtain.html. (accessed 26 June 2013).
  16. US National Library of Medicine: / MeSH record types. www.nlm.nih.gov/mesh/intro_record_types.html. (accessed 1 July 2013).
  17. Orphanet Consortium: / Rare diseases and cross-referencing. www.orphadata.org/cgi-bin/inc/product1.inc.php. (accessed 21 June 2013).
  18. Office of Rare Diseases Research: / Genetic and Rare Diseases Information Center. http://rarediseases.info.nih.gov/gard. (accessed 26/06/2013).
  R: A Language and Environment for Statistical Computing. R Foundation for Statistical Computing, Vienna, Austria
  19. ClinicalTrials.gov: / Protocol Data Element Definitions (draft). http://prsinfo.clinicaltrials.gov/definitions.html. (accessed 1 July 2013).
  20. Mitsumoto, J, Dorsey, ER, Beck, CA, Kieburtz, K, Griggs, RC (2009) Pivotal studies of orphan drugs approved for neurological diseases. Ann Neurol 66: pp. 184-190 CrossRef
  21. Ger脽, W, K枚pcke, W Clinical Trials and Rare Diseases. In: Paz Posada, M, Groft, SC eds. (2010) Rare Diseases Epidemiology. Springer, Netherlands, pp. 173-190 CrossRef
  22. Richesson, RL, Sutphen, R, Shereff, D, Krischer, JP (2012) The rare diseases clinical research network contact registry update: features and functionality. Contemp Clin Trials 33: pp. 647-656 CrossRef
  23. Putzeist, M, Heemstra, HE, Garcia, JL, Mantel-Teeuwisse, AK, Gispen-De Wied, CC, Hoes, AW, Leufkens, HG (2012) Determinants for successful marketing authorisation of orphan medicinal products in the EU. Drug Discov Today 17: pp. 352-358 CrossRef
  24. Heemstra, HE, Leufkens, HG, Rodgers, RP, Xu, K, Voordouw, BC, Braun, MM (2011) Characteristics of orphan drug applications that fail to achieve marketing approval in the USA. Drug Discov Today 16: pp. 73-80 CrossRef
  25. Day, S (2010) Evidence-based medicine and rare diseases. Adv Exp Med Biol 686: pp. 41-53 CrossRef
  26. Spodick, DH (1983) Randomize the first patient: scientific, ethical, and behavioral bases. Am J Cardiol 51: pp. 916-917 CrossRef
  27. Cornu, C, Kassai, B, Fisch, R, Chiron, C, Alberti, C, Guerrini, R, Rosati, A, Pons, G, Tiddens, H, Chabaud, S, Caudri, D, Ballot, C, Kurbatova, P, Castellan, AC, Bajard, A, Nony, P (2013) Experimental designs for small randomised clinical trials: an algorithm for choice. Orphanet J Rare Dis 8: pp. 48 CrossRef
  28. Gupta, S, Faughnan, ME, Tomlinson, GA, Bayoumi, AM (2011) A framework for applying unfamiliar trial designs in studies of rare diseases. J Clin Epidemiol 64: pp. 1085-1094 CrossRef
  29. Lilford, RJ, Thornton, JG, Braunholtz, D (1995) Clinical trials and rare diseases: a way out of a conundrum. BMJ 311: pp. 1621-1625 CrossRef
  30. Chow, SC, Chang, M (2008) Adaptive design methods in clinical trials - a review. Orphanet J Rare Dis 3: pp. 11 CrossRef
  31. Reaves, ND (2003) A model of effective health policy: the 1983 Orphan Drug Act. J Health Soc Pol 17: pp. 61-71 CrossRef
  32. Tambuyzer, E (2010) Rare diseases, orphan drugs and their regulation: questions and misconceptions. Nat Rev Drug Discov 9: pp. 921-929 CrossRef
  33. Dupont, AG, Wilder, PB (2011) Access to orphan drugs despite poor quality of clinical evidence. Br J Clin Pharmacol 71: pp. 488-496 CrossRef
  
• 刊物主题：Medicine/Public Health, general; Pharmacology/Toxicology; Medicinal Chemistry;
• 出版者：BioMed Central
• ISSN：1750-1172

文摘

Objectives To provide a comprehensive characterisation of rare disease clinical trials registered in ClinicalTrials.gov, and compare against characteristics of trials in non-rare diseases. Design Registry based study of ClinicalTrials.gov registration entries. Methods The ClinicalTrials.gov registry comprised 133,128 studies registered to September 27, 2012. By annotating medical subject heading descriptors to condition terms we could identify rare and non-rare disease trials. A total of 24,088 Interventional trials registered after January 1, 2006, conducted in the United States, Canada and/or the European Union were categorised as rare or non-rare. Characteristics of the respective trials were extracted and summarised with comparative statistics calculated where appropriate. Main outcome measures Characteristics of interventional trials reported in the database categorised by rare and non-rare conditions to allow comparison. Results Of the 24,088 trials categorised 2,759 (11.5%) were classified as rare disease trials and 21,329 (88.5%) related to non-rare conditions. Despite the limitations of the database we found that rare disease trials differed to non-rare disease trials across all characteristics that we examined. Rare disease trials enrolled fewer participants (median 29 vs. 62), were more likely to be single arm (63.0% vs. 29.6%), non-randomised (64.5% vs. 36.1%) and open label (78.7% vs. 52.2%). A higher proportion of rare disease trials were terminated early (13.7% vs. 6.3%) and proportionally fewer rare disease studies were actively pursuing, or waiting to commence, enrolment (15.9% vs. 38.5%). Conclusion Rare disease interventional trials differ from those in non-rare conditions with notable differences in enrolment, design, blinding and randomisation. However, clinical trials should aim to implement the highest trial design standards possible, regardless of whether diseases are rare or not.