Validation of Instruments for Assessing Drug Safety Management During the Conduction of Clinical Trials

Document Type : Original Article

Authors

1 Group of Health Technology Assessment, Institute of Molecular Immunology, Havana, Cuba

2 Research Department, Joaquin Castillo Duany’s Hospital, Santiago de Cuba, Cuba

Abstract

Background
The management of drug safety with the collection of reliable safety data during the conduction of clinical trials conduct is essential for the registry and marketing of products. The systematic evaluation of this process, based on objective measures, requires the application of quality instruments. This study was aimed to design and validate eight instruments through the components of quality (structure, process, and results), for characterizing and assessing the process of drug safety management, during the conduction of clinical trials.

 
Methods
The eight instruments were designed according to the international recommendations for Good Clinical Practice (GCP) and comprise a knowledge survey for professionals at the investigational sites, a satisfaction scale of internal and external clients and a satisfaction survey for patients with the treatment of the adverse events. The instruments also include a checklist to evaluate the safety management infrastructure (human, material and organizational resources) in the sponsoring center, a checklist to evaluate the same criterion at the investigational sites and three checklists that evaluate adherence to regulatory requirements of essential documents (investigator’s brochure, protocol, and informed consent form). The content validity was evaluated by Delphi method and the reliability was determined by Cronbach α test.

 
Results
All the items were valued as very adequate after the second round of the expert panel. The instruments were deemed as appropriate and understandable in the pre-test performed. All responders agreed with the options given and the accessibility of the application. Only 10% of professionals at the research sites suggested that the knowledge survey was too long. Cronbach α values between .66 and .93 were obtained.

 
Conclusion
The structure, process, and outcome framework allowed for the characterization of drug safety management during clinical trials, providing a useful approach for the promoter to systematically measure and evaluate the process. The eight instruments were deemed as reliable, feasible and easy to be used for examining drug safety management while carrying out clinical trials.

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Keywords

Main Subjects

References

  1. Francis D, Roberts I, Elbourne DR, et al. Marketing and clinical trials: a case study. Trials. 2007;8:37. doi:10.1186/1745-6215-8-37
  2. Outsourcing clinical trial data management. Clinical Trials. http://www.sciformix.com/wp-content/uploads/Outsourcing-Clinical-Trial-Safety-Data-Management-July-2014.pdf.   Accessed May 17, 2016. Published 2014.
  3. Dagalur S.  CTMS: What you should know. Applied Clinical Trials website. http://www.appliedclinicaltrialsonline.com/clinical-trial-management-systems-what-you-should-know.      Accessed May 29, 2016. Published 2016.
  4. Simplify, Streamline, Standardize: CTMS transforms the management of clinical research. Mayo Clinic website. http://www.mayo.edu/research/labs/clinical-trials-management-system/overview.     Accessed May 29, 2016.
  5. Oracle Argus Safety. Oracle data sheet, 2009. http://www.epharmaday.org/download/Oracle%20Argus%20Safety%203%20Pages.pdf.    Accessed May 29, 2016.
  6. Rodríguez L, Hernández MD, Díaz R, Martínez E, Hernández L, González L. ALASCLÍNICAS: Clinical trial management system. RCIM. 2012;4(1):5-16.
  7. Álvarez M, Corrales E, Viada C. Desarrollo de un modelo estándar de Eventos Adversos para el software AlasClinicas. Editorial Académica Española. https://businessarticles2011.info/211220929-desarrollo-de-un-modelo-estandar-de-ea-para-el-software-alasclinicas-by-alvarez-cardona-mabel.html.  Accessed May 29, 2016. Published 2013.
  8. Smith MY, Benattia I. The patient’s voice in pharmacovigilance: pragmatic approaches to building a patient-centric drug safety organization. Drug Saf. 2016;39:779-785. doi:10.1007/s40264-016-0426-9
  9. Sasaki H, Doi H, Ishii T, et al. Establishment and effect of the drug safety management monitoring system. Yakugaku Zasshi. 2003;123(10):893-900.
  10. Raizada M. Technology – a boon to drug safety industry trends and the importance of Drug safety. Pharma Times. 2015;47(08):22-24.
  11. Chuang-Stein C, Xia HA. The practice of pre-marketing safety assessment in drug development. J Biopharm Stat. 2013;23:3-25. doi:10.1080/10543406.2013.736805
  12. Rowe J, Calaprice-Whitty D. Quality Metrics for Clinical Trials. Applied Clinical Trials website. 2015. http://www.appliedclinicaltrialsonline.com/quality-metrics-clinical-trials.  Accessed July 29, 2017. Published 2015.
  13. Singh S, Loke YK. Drug safety assessment in clinical trials: methodological challenges and opportunities. Trials. 2012(13):138. doi:10.1186/1745-6215-13-138  
  14. Maennl U. Pharmacovigilance: A Company-Wide Challenge. Applied Clinical Trials website. http://www.appliedclinicaltrialsonline.com/pharmacovigilance-company-wide-challenge.  Accessed May 29, 2016. Published 2008.
  15. Safety Research Interest Group (SRIG) of the Center for Drug Evaluation and Research (CDER). Assessing CDER’s Drug Safety-Related Regulatory Science Needs and Identifying Priorities. https://www.fda.gov/downloads/drugs/scienceresearch/ucm438138.pdf.  Published 2015. 
  16. Swain E, Morgan S, Brewster W, Kauser S. Early communication of drug safety concerns: a feasibility study on enhancing interaction between the pharmaceutical industry and regulators. Pharmacoepidemiol Drug Saf. 2010;19:232-237. doi:10.1002/pds.1898
  17. Yao B, Zhu L, Jiang Q, Xia HA. Safety Monitoring in Clinical Trials. Pharmaceutics. 2013;5(1):94–106.  doi:10.3390/pharmaceutics5010094
  18. Food and Drug Administration (FDA). Guidance for Industry, Premarketing Risk Assessment. http://www.fda.gov/downloads/RegulatoryInformation/Guidances/ucm126958.pdf.   Accessed  October 9, 2016. Published 2005.
  19. Food and Drug Administration (FDA). Guidance for Industry, Development and Use of Risk Minimization Action Plans. http://www.fda.gov/downloads/RegulatoryInformation/Guidances/UCM126830.pdf.  Accessed October 9, 2016. Published 2005.
  20. Food and Drug Administration (FDA). Guidance for Industry, Good Pharmacovigilance Practices and Pharmacoepidemiologic Assessment. http://www.fda.gov/downloads/RegulatoryInformation/Guidances/UCM126834.pdf.  Accessed October 9, 2016. Published 2005.
  21. Crowe BJ, Xia HA, Berlin JA, et al. Recommendations for safety planning, data collection, evaluation and reporting during drug, biologic and vaccine development: A report of the safety planning, evaluation and reporting team. Clin Trials. 2009;6:430-440. doi:10.1177/1740774509344101
  22. Johnson T, Joyner M, DePourcq F, et al. Using research metrics to improve timelines: proceedings from the 2nd Annual CTSA Clinical Research Management Workshop. Clin Transl Sci. 2010;3(6):305-308. doi:10.1111/j.1752-8062.2010.00246.x
  23. García VM, Suárez MM. El método Delphi para la consulta a expertos en la investigación científica. Rev Cubana Salud Pública. 2013;39(2):253-267.
  24. Cardona JA, Luján JA. Construcción y validación de escalas de medición en salud: revisión de propiedades psicométricas. Arch Med. 2015;11(3).
  25. Calabuig F,  Crespo J. Uso del método Delphi para la elaboración de una medida de calidad percibida de los espectadores de eventos deportivos. Revista Retos Nuevas tendencias en Educación Física Deporte y Recreación. 2009;(15):21-25.
  26. Otero J, Jaime I, Otero I. Avedis Donabedian y la calidad de la atención de salud. http://www.gerenciasalud.com.  Accessed May 12, 2016.
  27. International Conference on Harmonisation. E6 (R1)- Good Clinical Practice: consolidated guidelines, Step 5. https://www.ich.org/fileadmin/Public_Web_Site/ICH_Products/Guidelines/Efficacy/E6/E6_R1_Guideline.pdf.  Accessed July 30 , 2017. Published May 1996.
  28. Council for International Organizations of Medical Sciences. Working Group VI. Geneva: CIOMS; 2005. https://cioms.ch/wp-content/uploads/2017/01/Mgment_Safety_Info.pdf.   Accessed July 15, 2017.
  29. Hurtado S. Criterio de expertos. Su procesamiento a través del método Delphy. http://www.ub.es/histodidactica/Epistemolog%EDa/Delphy.htm.   Accessed May 29, 2016. Published 2002.
  30. Hernández R, Fernández C, Baptista P. Metodología de la investigación. 5th ed. New York: McGraw-Hill/Interamericana; 2006:256-266.
  31. Holey EA, Feeley JL, Dixon J, Whittaker VJ. An exploration of the use of simple statistics to measure consensus and stability in Delphi studies. BMC Med Res Methodol. 2007;7:52. doi:10.1186/1471-2288-7-52
  32. Morales P. La fiabilidad de los tests y escalas. Madrid: Universidad Pontificia; 2007. http://www.upcomillas.es/personal/peter/estadisticabasica/Fiabilidad.pdf.   Accessed May 12, 2016.  
  33. Moráguez Iglesias A. El método Delphi. http://www.gestiopolis.com/canales6/eco/metodo-delphi-estadistica-de-investigacion-cientifica.htm.   Accessed May 12, 2016.
  34. Moraes CL, Reichenheim ME. Cross-cultural measurement equivalence of the Revised Conflict Tactics Scales. Portuguese version used to identify violence within couples. Cad Saúde Publica. 2002;18:783-796
  35. Rajadhyaksha V. Training for clinical research professionals: Focusing on effectiveness and utility. Perspect Clin Res. 2010;1(4):117-119. doi:10.4103/2229-3485.71767
  36. Horner E,  Kline B. Ensuring quality throughout the clinical process. Life Science Leader. Available from: https://www.clinicalleader.com/doc/ensuring-quality-throughout-the-clinical-process-0001.  Accessed May 29, 2016.   Published December 2010.
  37. Nelson G. Implementing Metrics Management for Improving Clinical Trials Performance. Beye Network. July 2008. Online. http://www.b-eye-network.com/view/7981.  Accessed July 29, 2016.  
  38. Ruiz TR. Utilización del Método de los expertos Delfos para la validación de una estrategia pedagógica. Órbita Científica. 2012;18(69):12. [Spanish].
  39. Boulkedid R, Abdoul H,  Loustau M, Sibony O, Alberti C. Using and reporting the Delphi method for selecting healthcare quality indicators: a systematic review. PLoS One. 2011;6(6):e20476. doi:10.1371/journal.pone.0020476

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History

  • Receive Date: 27 January 2017
  • Revise Date: 28 November 2017
  • Accept Date: 03 December 2017
  • First Publish Date: 01 July 2018

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