PREP Course # 17 Integrating Quality in Research II

Study Conduct

Presented by: Evelyn Huang & Leah Shuchter Office of Research Compliance

CME Disclosure Statement • The North Shore LIJ Health System adheres to the ACCME’s new

Standards for Commercial Support. Any individuals in a position to control the content of a CME activity, including faculty, planners, and managers, are required to disclose all financial relationships with commercial interests. All identified potential conflicts of interest are thoroughly vetted by the North Shore-LIJ for fair balance and scientific objectivity and to ensure appropriateness of patient care recommendations.

• Course Director and Course Planners: Kevin Tracey, MD, Cynthia Hahn, Emmelyn Kim, MPH, and Tina Chuck, MPH have nothing to disclose.

• Course Speakers: Evelyn Huang and Leah Shuchter have nothing to disclose

Course Objectives

Identify essential quality elements when conducting a research study. Acquire techniques to embed quality controls and assurance into a research framework.

Topics Covered

•Building an effective internal quality system for research program

•Commonly overlooked aspects of conducting a study

Key Elements to Build an Effective Internal Quality System for a Research Program

A. Setting quality standards B. Building quality control checks into a study at

the early stage C. Monitoring and measuring internal quality

systems throughout the study D. Sustaining competencies of staff E. CAPA and Continuing Improvement Process

What are Quality & Quality System?

• Quality: the total set of characteristics of a product or service that affect its ability to satisfy a customer's stated or implied needs.

• Quality system: the organizational structure, responsibilities, procedures, processes, and resources for implementing quality management 2

Set Quality Standards

• Regulatory requirements: FDA, HIPAA, DOD, NIH, State law, etc.

• Best practices: GCP/ALCOA/ ISO14155 • Institutional policies • Sponsor expectations

Quality Guidance - GCP

• All clinical trial information should be recorded, handled, and stored in a way that allows it’s accurate reporting, interpretation, and verification. (GCP 2.10)

• Systems with procedures that assure the quality of every aspect of the trial should be implemented. (GCP 2.13)

Tips for Setting the Standard

Change the Culture! A research program cannot achieve success without

first addressing the “Culture” that impacts the activities, the ability, and the desire to be compliant with all the different requirements. 2

Creating an environment in which each individual understands their role in the research enterprise and conducts their activities in a responsible manner. 2

What are QC & QA?

Quality Control: reviewing the details (viewing the tree) Quality Assurance: testing the systems (viewing the forest)

QC and QA

Both quality control and quality assurance are parts of quality management.

• Quality control (QC): periodic operational checks within each functional department to verify that clinical data are generated, collected, handled, analyzed, and reported according to protocol, SOPs, and GCPs.1

• Quality assurance (QA): the systematic and independent examination of all trial-related activities and documents. These audits determine whether the evaluated activities were appropriately conducted and that the data were generated, recorded, analyzed, and accurately reported according to protocol, standard operating procedures (SOPs), and good clinical practices (GCPs).1

The Shewhart Model – the Best Guide for Ensuring Quality is Inherent in Every Aspect of the Process 3

Building QC Checks Into a Study Early On

For study sites, the following QC checks can be built in the plan as early as possible:

• Operational QC • Data Management QC

Operational QC - 1

• SOP, MOP, Pharmacy Manual: standardized process throughout the program/study

• Document management to be used for QC at each operational stage : CRFs, source documents template, checklists, DARF, subject medication diary, etc

Operational QC-2

• Communication plan- effective communication: regular meeting with the sponsor/medical monitor, regular research team staff meeting,

• Self monitoring plan-how to evaluate if your program works efficiently and normally: regular review of study application process and timeframe, DSMB/DSMC, protocol compliance

• Study monitoring plan for sponsor-investigator held IND/IDEs: how to monitor for protocol compliance? How to validate the data?

Data Management QC-1

Data entry, cross-check and verification plan: 1. Data entry time frames & expectations 2. Delegating an independent data entry person to

enter data, and another person to review and verify data (CRF vs. Source) on a regular basis

3. For electronic databases, as data is entered, the database can be QC'd by comparing the database to the CRFs from which the data was entered.

Data Management QC-2

• Data Cleaning-Query Resolution: Work closely with the study monitor, data coordination center or delegated QC reviewer, to resolve queries timely if applicable.

• Data Report: When designing a database, build controls in the system: error alert, query report analysis, deviation rate/type report, enrollment report, etc.

Tips for QC

• Plan- Appropriate planning during the trial • Do- Adequate oversight, delegation, and

training during the trial • Check- Self-verification/monitoring to ensure

compliance with study, regulation, and institutional policies requirements

• Act- revise your SOP, protocol, ICF, MOP or etc timely

QA- Monitoring and Measuring Internal Quality Systems Throughout the Study

• An internal QA plan is important for a successful research program and includes the activities to be conducted throughout the clinical trial

• QA will focus on the bigger picture and not only

one aspect

"What gets measured, gets managed." - Peter Drucker

QA Process Plan: Plan for the internal audit/self-check?

– What needs to be self-audited/reviewed? Why? Risk Assessment? When?

Process: Standardize the processes for the internal audit?

- Who will conduct the audit? Delegation, training, tools, processes, etc.

Analyze: Analyze your audit data and see of your research program is

working well – How to interpret the findings/results?

Action: Actions to be implemented after the QA review? - How to make changes on the study based on the QA review?

Tips for QA

• A key person who is responsible for the QA activities – qualified and properly trained

• Tools and templates for QA activities- ORC website or “Google it”

• Utilize the QA findings for improvements to the program – SOP, MOP, policies, etc

• Obtain support and resources from departmental leadership/ administration

Sustaining Competencies of Staff

• Set the performance standard for your research program at the beginning: qualification, experience, etc.

• Have a written plan for key personnel coverage • Have a plan for continuing education/training process

and assess the adequacy of training: protocol training, professional training/certification, human subject protection and GCP training, conferences and meetings, etc.

• Have a process to validate the competencies : annual quiz on the research topics, annual performance review, license / certificate renewal, etc.

CAPA and Continuing Improvement Process-1

Corrective And Preventive Action Plans • The purpose: to ensure that complaints,

discrepancies, and non-compliance are visible, prioritized, and tracked, and that the root cause is determined and resolved.

• A system to track issues of noncompliance that have not been resolved.

• It requires identifying a person responsible for defining and tracking the process.

Remember the 5 Why’s!

CAPA and Continuing Improvement Process-2

The continual improvement process • What is the goal for improvement? • What are the processes? • Who is watching them? • When to evaluate the processes? How? • What is the next goal?

Commonly Overlooked Aspects of Conducting a Study

• Issue escalation process: abnormal lab findings / exam result, what can you do?

• Cooperate with other departments/team: data management team, study monitors, IRB, etc.

• Be sensitive with research subjects’ experience with the study - cultural competency, discuss responsibilities

• Stay alert with regulation or institutional policies changes

Case Study A research team was audited by the sponsor for a

phase 2 randomized trial. During the review, major issues related to the informed consent and randomization were identified:

a. Executed consent forms missing, expired consent version used (major change of the study procedures), re-consent was not obtained after the new risk information was available, etc.

b. Randomization assignment record did not match the 3 subjects’ treatment records

What can they do?

Tips: adapted from http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3227329/?report=classic

Plan Identify the error in the process. The root-cause-analysis would consider the process employed by the personnel authorized and their training. The plan would focus on re-training the persons who have committed the error.

Do This step would require applying the planned changes. This

means re-training the persons who have committed the error.

Check This would require monitoring of the consent and

randomization process, to check whether the errors continue, by observing the staff during the process and

auditing a select number of records.

Act If all records are signed and dated, then the plan could be

applied to the whole team. If the errors persist, the cycle is repeated

What did the team do?

Plan: Study enrollment was put on hold. Develop a comprehensive CAPA for the issues

Do: implement all the changes for the informed consent and randomization process and documentation: new form & template to be used, cross check, etc

Check: have a delegated person who is independent from the study conduct the routine self-audit

Act: no more major issues for the audits occurred after the CAPA implemented, and SOP is finalized

Issues were resolved!

Questions and Comments?

Research is all about Quality

YOU are the owner of the internal quality system for your research program! Start from today!

References 1. http://www.appliedclinicaltrialsonline.com/appliedclinicaltrials/CRO

%2FSponsor+Articles/Quality-Control-and-Assurance-in-Clinical-Research/ArticleStandard/Article/detail/310811

2. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3088954/ 3. http://www.pfizer.com/files/research/research_clinical_trials/Qualit

yManagement_ClinicalTrials_030209.pdf 4. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3227329/?report=cl

assic

Acknowledgements Thank you to Lori Megherian, Janith Stieb and Emmelyn

Kim for assisting in the development of this presentation

Office of Research Compliance

Evelyn Huang Manager, Office of Research Compliance

(516) 321-2110 ehuang2@nshs.edu

Leah Shuchter Manager, Office of Research Compliance

(516) 321-2109 lshuchter@nshs.edu