Copyright (c) 2020 Mohammad Younis Bhat
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.
Role of Quality Assurance and Quality Control in Clinical Trials – Need for Harmonization
Corresponding Author(s) : Mohammad Younis Bhat
International Journal of Allied Medical Sciences and Clinical Research,
Vol. 3 No. 1 (2015): 2015 Volume 3- Issue -1
Abstract
Clinical trials may be defined as biomedical or health related research studies in human beings that follows a pre-defined protocol. Clinical trials are the link between the results of preclinical testing and actual clinical practice. They are conducted to collect the data necessary to provide information for academia, industry and regulators and it is only through trials that progress is made on new medicines including drugs, vaccines, and devices, as well as improved treatments for diseases. Clinical trials involves interplay between clinical investigators (often referred as Principal Investigator or PI), patients, sponsors, control research organization (CRO), clinical laboratories with the overall objective of improving healthcare to ensure subject safety, validity, accuracy and credibility of data generated. To ensure that these concerns are adequately addressed in a study, regulations and guidelines have been developed like following the protocol, complying with regulatory and Good Clinical Practice (GCP) standards, collecting and reporting quality data and overall monitoring of the progress of trial. Maintaining accuracy and quality throughout the clinical study is a continuous dynamic process. There is increasing focus on having quality system in place throughout the planning stages of clinical trials with specific standards for each clinical trial process to produce a more reliable and useful end product – high quality data without compromising the rights and welfare of human subjects. Globalization, outsourcing and increasing complexity of clinical trials have made the target of achieving global quality challenging. Although the study requirements are carefully set forth initially, expectation and requirements can change during a study and coordination and harmonization throughout the trial is essential.
Keywords
Clinical trials
academia
industry
regulators
control research organization (CRO)
Good Clinical Practice (GCP)
References
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[1] Freedland KE, Carney RM. Data management and accountability in behavioral and biomedical research. Am Psychol 1992; 47: 640-5.
[2] Gassman JJ, Owen WW, Kuntz TE, et al. Data quality assurance, monitoring, and reporting. Control Clin Trials 1995; 16(2 Suppl): 104S-36S.
[3] Prud'homme GJ, Canner PL, Cutler JA. Quality assurance and monitoring in the Hypertension Prevention Trial. Hypertension Prevention Trial Research Group. Control Clin Trials 1989; 10(3 Suppl): 84S-94S.
[4] Karrison T. Data editing in a clinical trial. Control Clin Trials 1981; 2: 15-29.
[5] Marinez YN, McMahan CA, Barnwell GM, et al. Ensuring data quality in medical research through an integrated data management system. Stat Med 1984; 3: 101-ll.
[6] Bagniewska A, Black D, Molvig K, et al. Data quality in a distributed data processing system: the SHEP Pilot Study. Control Clin Trials 1986; 7: 27-37.
[7] Severe JB, Schooler NR, Lee JH, et al. Ensuring data quality in a multicenter clinical trial: remote site data entry, central coordination and feedback. Psychopharmacol Bull 1989; 25: 488-90.
[8] Sforza VA. Quality data: what are they? Ann 1st Super Sanita 1994; 30: 439-43.
[9] Hohnloser JH, Puerner F, Soltanian H. Improving coded data entry by an electronic patient record system. Methods Inf Med 1996; 35: 108-11.
[10] Canner PL, Borhani NO, Oberman A, et al. The Hypertension Prevention Trial: assessment of the quality of blood pressure measurements. Am J Epidemiol 1991; 134: 379-92.
[11] Keltner JL, Johnson CA, Beck RW, et al. Quality control functions of the Visual Field Reading Center (VFRC) for the Optic Neuritis Treatment Trial (ONTT). Control Clin Trials 1993; 14: 143-59.
[12] Habig RL, Thomas P, Lippel K, et al. Central laboratory quality control in the National Cooperative Gallstone Study. Control Clin Trials 1983; 4: 101-23.
[13] Correa A, Stewart WF, Yeh HC, et al. Exposure measurement in case-control studies: reported methods and recommendations. Epidemiol Rev 1994; 16: 18-32.
[14] Bergman LR. Measurement and data quality in longitudinal research. Eur Child Adolesc Psychiatry 1996; 5(Suppl 1): 28-32.
[15] Johstone FD, Brown MC, Campbell D, et al. Measurement of variables: data quality control. Am J Clin Nutr 1981; 34(Suppl 4): 804-6.
[16] Tillotson JL, Gorder DD, DuChene AG, et al. Quality control in the Multiple Risk Factor Intervention Trial Nutrition Modality. Control Clin Trials 1986; 7(3 Suppl): 66S-9OS.
[17] Dischinger P, DuChene AG. Quality control aspects of blood pressure measurements in the Multiple Risk Factor Intervention Trial. Control Clin Trials 1986; 7(3 Suppl): 137S-57S.
[18] Cooper GR, Haff AC, Widdowson GM, et al. Quality control in the MRFIT local screening and clinic laboratory. Control Clin Trials 1986; 7(3 Suppl): 158S-65S.
[19] Neaton JD, Duchene AG, Svendsen KH, et al. An examination of the efficiency of some quality assurance methods commonly employed in clinical trials. Stat Med 1990; 9: 115-24.
[20] van der Putten E, van der Velden JW, Siers A, et al. A pilot study on the quality of data management in a cancer clinical trial. Control Clin Trials 1987; 8: 96-100.
[21] FDA ORA Quality Manual. http://www.fda.gov/AboutFDA/Centers Offices/ORA/UCM 135836.htm
[22] A Guided Self-Assessment for Human Research Protection Programs. http://www.hhs.gov/ohrp/qi/.
[23] Salewski JP. FDA Expectations of Clinical Trials and Investigators. [Last accessed 2011 Mar 1]. Available from: http://www.fda.gov/downloads/ScienceResearch/ SpecialTopics/CriticalPathInitiative/Spotlighto nCPIProjects/UCM236735.ppt.
[24] US FDA Information Sheet Guidance for IRBs, Clinical Investigators, and Sponsors FDA Inspections of Clinical Investigators. [Last accessed on 2011 Aug 08]. Available from: http://www.fda.gov/downloads/RegulatoryInformation /Guidances/UCM126553.pdf.
[25] Lou A. Preparing for an FDA Medical Device Sponsor Inspection. [Last accessed on 2011 Jul 28]. Available from: http://www.fda.gov/downloads/Training /CDRHLearn/UCM176843.pdf .
[26] Korieth K. Spike in warning letters sends tremors through industry. Centerwatch Mon. 2010; 17: 1–9.
[27] Lou A. Preparing for an FDA Institutional Review Board Inspection. [Last accessed on 2011 Jul 28]. Available from: http://www.fda.gov/Training/CDRHLearn/ ucm180891.htm.
[28] Kleppinger CF, Ball LK. Building Quality in clinical trials with use of a quality systems approach. Clin Infect Dis. 2010; 51(Suppl 1): S111–6.
[29] Research needs quality management. Article, quality management. http:///www.therqa.com/assets/js/tiny_mce/plugins/ilemanager/iles/Committees/Quality/Research_needs_quality_management_system.pdf.
[30] Ann Meeker-O’Connell. Enhancing clinical trial quality: CDER perspective. http:///www.fdanews.com/ext/iles/conference/FIS10Presentations/MeekerOConnell-HarmonizingRegulatoryApproaches.pdf.
[31] Clinical Trials Transformation Initiative (CTTI): Conducting Multicenter Clinical Trials: New Recommendations and Tool for Research. http://www.ctti-clinicaltrials.org/.
[32] Clinical Trials Transformation Initiative. Scope statement. http://www. trialstransformation.org/scope.
[33] Code of Federal Regulations Title 21. US Food and Drug Administration, Department of Health and Human Services. Subchapter H: medical devices. Part 812 – investigational device exemptions. Subpart C: responsibilities of sponsors. Sec 812.40. General responsibilities of sponsors. http://frwebgate. access.gpo.gov/cgi-bin/get cfr.cgi?TITLEp21@PARTp812&SECTIONp40&TYPEp TEXT
[34] Arun Bhatt. Quality of clinical trials: A moving target. Perspectives in Clinical Research. 2011. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3227329/.
References
[1] Freedland KE, Carney RM. Data management and accountability in behavioral and biomedical research. Am Psychol 1992; 47: 640-5.
[2] Gassman JJ, Owen WW, Kuntz TE, et al. Data quality assurance, monitoring, and reporting. Control Clin Trials 1995; 16(2 Suppl): 104S-36S.
[3] Prud'homme GJ, Canner PL, Cutler JA. Quality assurance and monitoring in the Hypertension Prevention Trial. Hypertension Prevention Trial Research Group. Control Clin Trials 1989; 10(3 Suppl): 84S-94S.
[4] Karrison T. Data editing in a clinical trial. Control Clin Trials 1981; 2: 15-29.
[5] Marinez YN, McMahan CA, Barnwell GM, et al. Ensuring data quality in medical research through an integrated data management system. Stat Med 1984; 3: 101-ll.
[6] Bagniewska A, Black D, Molvig K, et al. Data quality in a distributed data processing system: the SHEP Pilot Study. Control Clin Trials 1986; 7: 27-37.
[7] Severe JB, Schooler NR, Lee JH, et al. Ensuring data quality in a multicenter clinical trial: remote site data entry, central coordination and feedback. Psychopharmacol Bull 1989; 25: 488-90.
[8] Sforza VA. Quality data: what are they? Ann 1st Super Sanita 1994; 30: 439-43.
[9] Hohnloser JH, Puerner F, Soltanian H. Improving coded data entry by an electronic patient record system. Methods Inf Med 1996; 35: 108-11.
[10] Canner PL, Borhani NO, Oberman A, et al. The Hypertension Prevention Trial: assessment of the quality of blood pressure measurements. Am J Epidemiol 1991; 134: 379-92.
[11] Keltner JL, Johnson CA, Beck RW, et al. Quality control functions of the Visual Field Reading Center (VFRC) for the Optic Neuritis Treatment Trial (ONTT). Control Clin Trials 1993; 14: 143-59.
[12] Habig RL, Thomas P, Lippel K, et al. Central laboratory quality control in the National Cooperative Gallstone Study. Control Clin Trials 1983; 4: 101-23.
[13] Correa A, Stewart WF, Yeh HC, et al. Exposure measurement in case-control studies: reported methods and recommendations. Epidemiol Rev 1994; 16: 18-32.
[14] Bergman LR. Measurement and data quality in longitudinal research. Eur Child Adolesc Psychiatry 1996; 5(Suppl 1): 28-32.
[15] Johstone FD, Brown MC, Campbell D, et al. Measurement of variables: data quality control. Am J Clin Nutr 1981; 34(Suppl 4): 804-6.
[16] Tillotson JL, Gorder DD, DuChene AG, et al. Quality control in the Multiple Risk Factor Intervention Trial Nutrition Modality. Control Clin Trials 1986; 7(3 Suppl): 66S-9OS.
[17] Dischinger P, DuChene AG. Quality control aspects of blood pressure measurements in the Multiple Risk Factor Intervention Trial. Control Clin Trials 1986; 7(3 Suppl): 137S-57S.
[18] Cooper GR, Haff AC, Widdowson GM, et al. Quality control in the MRFIT local screening and clinic laboratory. Control Clin Trials 1986; 7(3 Suppl): 158S-65S.
[19] Neaton JD, Duchene AG, Svendsen KH, et al. An examination of the efficiency of some quality assurance methods commonly employed in clinical trials. Stat Med 1990; 9: 115-24.
[20] van der Putten E, van der Velden JW, Siers A, et al. A pilot study on the quality of data management in a cancer clinical trial. Control Clin Trials 1987; 8: 96-100.
[21] FDA ORA Quality Manual. http://www.fda.gov/AboutFDA/Centers Offices/ORA/UCM 135836.htm
[22] A Guided Self-Assessment for Human Research Protection Programs. http://www.hhs.gov/ohrp/qi/.
[23] Salewski JP. FDA Expectations of Clinical Trials and Investigators. [Last accessed 2011 Mar 1]. Available from: http://www.fda.gov/downloads/ScienceResearch/ SpecialTopics/CriticalPathInitiative/Spotlighto nCPIProjects/UCM236735.ppt.
[24] US FDA Information Sheet Guidance for IRBs, Clinical Investigators, and Sponsors FDA Inspections of Clinical Investigators. [Last accessed on 2011 Aug 08]. Available from: http://www.fda.gov/downloads/RegulatoryInformation /Guidances/UCM126553.pdf.
[25] Lou A. Preparing for an FDA Medical Device Sponsor Inspection. [Last accessed on 2011 Jul 28]. Available from: http://www.fda.gov/downloads/Training /CDRHLearn/UCM176843.pdf .
[26] Korieth K. Spike in warning letters sends tremors through industry. Centerwatch Mon. 2010; 17: 1–9.
[27] Lou A. Preparing for an FDA Institutional Review Board Inspection. [Last accessed on 2011 Jul 28]. Available from: http://www.fda.gov/Training/CDRHLearn/ ucm180891.htm.
[28] Kleppinger CF, Ball LK. Building Quality in clinical trials with use of a quality systems approach. Clin Infect Dis. 2010; 51(Suppl 1): S111–6.
[29] Research needs quality management. Article, quality management. http:///www.therqa.com/assets/js/tiny_mce/plugins/ilemanager/iles/Committees/Quality/Research_needs_quality_management_system.pdf.
[30] Ann Meeker-O’Connell. Enhancing clinical trial quality: CDER perspective. http:///www.fdanews.com/ext/iles/conference/FIS10Presentations/MeekerOConnell-HarmonizingRegulatoryApproaches.pdf.
[31] Clinical Trials Transformation Initiative (CTTI): Conducting Multicenter Clinical Trials: New Recommendations and Tool for Research. http://www.ctti-clinicaltrials.org/.
[32] Clinical Trials Transformation Initiative. Scope statement. http://www. trialstransformation.org/scope.
[33] Code of Federal Regulations Title 21. US Food and Drug Administration, Department of Health and Human Services. Subchapter H: medical devices. Part 812 – investigational device exemptions. Subpart C: responsibilities of sponsors. Sec 812.40. General responsibilities of sponsors. http://frwebgate. access.gpo.gov/cgi-bin/get cfr.cgi?TITLEp21@PARTp812&SECTIONp40&TYPEp TEXT
[34] Arun Bhatt. Quality of clinical trials: A moving target. Perspectives in Clinical Research. 2011. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3227329/.
[2] Gassman JJ, Owen WW, Kuntz TE, et al. Data quality assurance, monitoring, and reporting. Control Clin Trials 1995; 16(2 Suppl): 104S-36S.
[3] Prud'homme GJ, Canner PL, Cutler JA. Quality assurance and monitoring in the Hypertension Prevention Trial. Hypertension Prevention Trial Research Group. Control Clin Trials 1989; 10(3 Suppl): 84S-94S.
[4] Karrison T. Data editing in a clinical trial. Control Clin Trials 1981; 2: 15-29.
[5] Marinez YN, McMahan CA, Barnwell GM, et al. Ensuring data quality in medical research through an integrated data management system. Stat Med 1984; 3: 101-ll.
[6] Bagniewska A, Black D, Molvig K, et al. Data quality in a distributed data processing system: the SHEP Pilot Study. Control Clin Trials 1986; 7: 27-37.
[7] Severe JB, Schooler NR, Lee JH, et al. Ensuring data quality in a multicenter clinical trial: remote site data entry, central coordination and feedback. Psychopharmacol Bull 1989; 25: 488-90.
[8] Sforza VA. Quality data: what are they? Ann 1st Super Sanita 1994; 30: 439-43.
[9] Hohnloser JH, Puerner F, Soltanian H. Improving coded data entry by an electronic patient record system. Methods Inf Med 1996; 35: 108-11.
[10] Canner PL, Borhani NO, Oberman A, et al. The Hypertension Prevention Trial: assessment of the quality of blood pressure measurements. Am J Epidemiol 1991; 134: 379-92.
[11] Keltner JL, Johnson CA, Beck RW, et al. Quality control functions of the Visual Field Reading Center (VFRC) for the Optic Neuritis Treatment Trial (ONTT). Control Clin Trials 1993; 14: 143-59.
[12] Habig RL, Thomas P, Lippel K, et al. Central laboratory quality control in the National Cooperative Gallstone Study. Control Clin Trials 1983; 4: 101-23.
[13] Correa A, Stewart WF, Yeh HC, et al. Exposure measurement in case-control studies: reported methods and recommendations. Epidemiol Rev 1994; 16: 18-32.
[14] Bergman LR. Measurement and data quality in longitudinal research. Eur Child Adolesc Psychiatry 1996; 5(Suppl 1): 28-32.
[15] Johstone FD, Brown MC, Campbell D, et al. Measurement of variables: data quality control. Am J Clin Nutr 1981; 34(Suppl 4): 804-6.
[16] Tillotson JL, Gorder DD, DuChene AG, et al. Quality control in the Multiple Risk Factor Intervention Trial Nutrition Modality. Control Clin Trials 1986; 7(3 Suppl): 66S-9OS.
[17] Dischinger P, DuChene AG. Quality control aspects of blood pressure measurements in the Multiple Risk Factor Intervention Trial. Control Clin Trials 1986; 7(3 Suppl): 137S-57S.
[18] Cooper GR, Haff AC, Widdowson GM, et al. Quality control in the MRFIT local screening and clinic laboratory. Control Clin Trials 1986; 7(3 Suppl): 158S-65S.
[19] Neaton JD, Duchene AG, Svendsen KH, et al. An examination of the efficiency of some quality assurance methods commonly employed in clinical trials. Stat Med 1990; 9: 115-24.
[20] van der Putten E, van der Velden JW, Siers A, et al. A pilot study on the quality of data management in a cancer clinical trial. Control Clin Trials 1987; 8: 96-100.
[21] FDA ORA Quality Manual. http://www.fda.gov/AboutFDA/Centers Offices/ORA/UCM 135836.htm
[22] A Guided Self-Assessment for Human Research Protection Programs. http://www.hhs.gov/ohrp/qi/.
[23] Salewski JP. FDA Expectations of Clinical Trials and Investigators. [Last accessed 2011 Mar 1]. Available from: http://www.fda.gov/downloads/ScienceResearch/ SpecialTopics/CriticalPathInitiative/Spotlighto nCPIProjects/UCM236735.ppt.
[24] US FDA Information Sheet Guidance for IRBs, Clinical Investigators, and Sponsors FDA Inspections of Clinical Investigators. [Last accessed on 2011 Aug 08]. Available from: http://www.fda.gov/downloads/RegulatoryInformation /Guidances/UCM126553.pdf.
[25] Lou A. Preparing for an FDA Medical Device Sponsor Inspection. [Last accessed on 2011 Jul 28]. Available from: http://www.fda.gov/downloads/Training /CDRHLearn/UCM176843.pdf .
[26] Korieth K. Spike in warning letters sends tremors through industry. Centerwatch Mon. 2010; 17: 1–9.
[27] Lou A. Preparing for an FDA Institutional Review Board Inspection. [Last accessed on 2011 Jul 28]. Available from: http://www.fda.gov/Training/CDRHLearn/ ucm180891.htm.
[28] Kleppinger CF, Ball LK. Building Quality in clinical trials with use of a quality systems approach. Clin Infect Dis. 2010; 51(Suppl 1): S111–6.
[29] Research needs quality management. Article, quality management. http:///www.therqa.com/assets/js/tiny_mce/plugins/ilemanager/iles/Committees/Quality/Research_needs_quality_management_system.pdf.
[30] Ann Meeker-O’Connell. Enhancing clinical trial quality: CDER perspective. http:///www.fdanews.com/ext/iles/conference/FIS10Presentations/MeekerOConnell-HarmonizingRegulatoryApproaches.pdf.
[31] Clinical Trials Transformation Initiative (CTTI): Conducting Multicenter Clinical Trials: New Recommendations and Tool for Research. http://www.ctti-clinicaltrials.org/.
[32] Clinical Trials Transformation Initiative. Scope statement. http://www. trialstransformation.org/scope.
[33] Code of Federal Regulations Title 21. US Food and Drug Administration, Department of Health and Human Services. Subchapter H: medical devices. Part 812 – investigational device exemptions. Subpart C: responsibilities of sponsors. Sec 812.40. General responsibilities of sponsors. http://frwebgate. access.gpo.gov/cgi-bin/get cfr.cgi?TITLEp21@PARTp812&SECTIONp40&TYPEp TEXT
[34] Arun Bhatt. Quality of clinical trials: A moving target. Perspectives in Clinical Research. 2011. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3227329/.