The Life Cycle and Management of Protocol Deviations

Therapeutic Innovation and Regulatory Science

Volumn 48, Issue 6, 2014, Pages 762-777

  Mehra, Munish ^a   Kurpanek, Katharina ^b   Petrizzo, Maryrose ^c   Brenner, Sonia ^d   McCracken, Yvonne ^e   Katz, Terry ^f   Gurian, Margaret ^g  

^a Quantum BioPharma   (United States)

^b The QM Company   (Belgium)

^c Halloran Consulting Group   (United States)

^d KYOWA HAKKO KOGYO CO LTD   (Japan)

^e PMG Research Inc ^*  (United States)

^f MERCK ANIMAL HEALTH   (United States)

^g CompleWare Corp ^*  (United States)

Author keywords

corrective action; corrective action preventive action; departure; deviation; fraud; good clinical practice; noncompliance; preventive action; professional misconduct; protocol deviations; protocol violations; serious breach; variance; violation; waiver

Indexed keywords

ARTICLE; CLASSIFICATION; CLINICAL PROTOCOL; CLINICAL STUDY; CLINICAL TRIAL (TOPIC); DATA ANALYSIS; DRUG EFFICACY; DRUG INDUSTRY; DRUG SAFETY; GOOD CLINICAL PRACTICE; HUMAN; PATIENT ASSESSMENT; PATIENT SAFETY; PRIORITY JOURNAL; QUALITY CONTROL; RISK ASSESSMENT; STATISTICAL ANALYSIS; STUDY DESIGN;

EID: 84921023606     PISSN: 21684790     EISSN: 21684804     Source Type: Journal    
DOI: 10.1177/2168479014530119     Document Type: Article

References (25)

1. MARC Research. Top 5 FDA warning letters for clinical investigators. http://www.imarcresearch.com/top-5-2012-download/. Accessed April 23, 2012.
2. US Food and Drug Administration. Inspections, compliance, enforcement, and criminal investigations: enforcement actions, warning letter. http://www.fda.gov/ICECI/EnforcementActions/WarningLetters/ucm248222.htm. Updated March 28, 2011. Accessed November 8, 2013.
3. US Food and Drug Administration. Inspections, compliance, enforcement, and criminal investigations: enforcement actions, warning letters. http://www.fda.gov/ICECI/EnforcementActions/WarningLetters/default.htm. Updated November 4, 2013. Accessed October 22, 2013.
4. Secretary’s Advisory Committee on Human Research Protections. SACHRP minutes, February 28-29, 2012. http://www.hhs.gov/ohrp/sachrp/mtgings/2012%20Feb%20Mtg/meetingminutes.pdf. Accessed October 22, 2013.
5. US Food and Drug Administration. CFR: Code of Federal Regulations Title 21. http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm?fr=812.150. Updated April 1, 2013. Accessed October 23, 2013.
6. US Food and Drug Administration. Compliance program guidance manual: program 7348.811. http://www.fda.gov/downloads/ICECI/EnforcementActions/BioresearchMonitoring/UCM133773.pdf. Accessed October 23, 2013.
7. US Food and Drug Administration. Guidance for industry, investigator responsibilities: protecting the rights, safety, and welfare of study subjects. http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM187772.pdf. Accessed October 23, 2013.
8. International Standards Organization. Document 14155: clinical investigation of medical devices for human subjects—good clinical practice. http://www.unil.ch/webdav/site/fbm/shared/cercfbm/ISO-14155-2011.pdf. Published February 1, 2011. Accessed October 23, 2013.
9. International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use. E3 guideline: structure and content of clinical study reports, questions & answers. http://www.ich.org/fileadmin/Public_Web_Site/ICH_Products/Guidelines/Efficacy/E3/E3_QAs_R1_Step4.pdf. Published July 6, 2012. Accessed October 23, 2013.
10. International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use. E3 guideline: structure and content of clinical study reports. http://www.fda.gov/downloads/RegulatoryInformation/Guidances/UCM129456.pdf. Published July 1996. Accessed October 23, 2013.
11. Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) statement. http://www.spirit-statement.org/. Published January 30, 2013. Accessed October 23, 2013.
12. Clinical Data Interchange Standards Consortium. Organizing and accelerating the clinical research process from the beginning: the CDISC protocol representation model and toolkit. http://www.cdisc.org/stuff/contentmgr/files/0/58c41a172c8dc8863083b6ea233f1a54/misc/prm_document___april_2012fin.pdf. Published April 2012. Accessed October 23, 2013.
13. Sprenger K,Nickerson D,Meeker-O’Connell A,Morrison BW.Quality by design in clinical trials: a collaborative pilot with FDA [published online October 25, 2012].Drug Inf J.:
14. Kramer MJ,Grandinetti C,Kramer JM,Morrison BW,Ball L,Sherman RE.Clinical trials: rethinking how we ensure quality.Drug Inf J. 2012;46:657
15. Clinical Trials Transformation Initiative. Expert meeting summary, principles document. http://www.trialstransformation.org/what-we-do/investigational-plan/qbd-qrm/products. Accessed November 6, 2013.
16. US Food and Drug Administration. Guidance for industry: oversight of clinical investigations—a risk-based approach to monitoring. http://www.fda.gov/downloads/Drugs/./Guidances/UCM269919.pdf. Published August 2013. Accessed October 23, 2013.
17. European Medicines Agency. Reflection paper on risk based quality management in clinical trials. http://www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2013/11/WC500155491.pdf. Published November 18, 2013. Accessed November 28, 2013.
18. National Research Council of the National Academies. The prevention and treatment of missing data in clinical trials. http://www.nap.edu/openbook.php?record_id=12955&page=R1. Published 2010. Accessed October 23, 2013.
19. European Medicines Agency. Guideline on missing data in confirmatory clinical trials. http://www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2010/09/WC500096793.pdf. Published July 2, 2010. Accessed November 15, 2013.
20. European Medicines Agency. Home, regulatory, human medicines, inspections, GCP compliance, Q&A, GCP matters, response to question 1. http://www.ema.europa.eu/ema/index.jsp?curl=pages/regulation/q_and_a/q_and_a_detail_000016.jsp&mid=WC0b01ac05800296c5. Accessed October 23, 2013.
21. Federal Register. 2009;74 (153): 40211
22. European Medicines Agency. Reflection paper on risk based quality management in clinical trials. http://www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2013/11/WC500155491.pdf. Published November 18, 2013. Accessed November 28, 2013.
23. European Medicines Agency. Procedure for reporting of GCP inspections requested by the Committee for Medicinal Products for Human Use (CHMP). http://www.ema.europa.eu/docs/en_GB/document_library/Regulatory_and_procedural_guideline/2009/10/WC500004479.pdf. Published March 18, 2013. Accessed November 15, 2013.
24. Medicines and Healthcare Products Regulatory Agency. Guidance for the notification of serious breaches of GCP or the trial protocol, version 4 (Final 291013). http://www.mhra.gov.uk/home/groups/is-insp/documents/websiteresources/con060111.pdf. Published October 29, 2013. Accessed November 15, 2013.
25. Danish Health and Medicines Authority. Notification of serious or repeated non-compliance with good clinical practice in clinical trials. http://sundhedsstyrelsen.dk/en/medicines/regulation/clinical-trials/inspection-of-clinical-trials-gcp-inspection/notification-of-serious-or-repeated-non-compliance. Published August 25, 2010. Updated April 20, 2012. Accessed November 15, 2013.