Another new requirement from ISO/DIS 14155 (2009) Workshop presented by Dr. Nancy J Stark,available OnDemand
The revisions to ISO 14155 "Clinical investigation of medical devices in human subjects—good clinical practices" will bring sweeping changes to device clinical research everywhere. One of the new challenges for sponsors will be determining how to meet the requirements for clinical quality assurance and quality control. Here is an excerpt from ISO/DIS revisions published in September 2009.
Implement and maintain clinical quality procedures, maintain records, ensure auditing requirements, justify and document exceptions, integrate into the sponsor's overall quality system, and see ISO 13485 for more information? These are requirements for clinical research (CR) that do not exist today!
Crafting a Quality Management System for Clinical Research A useful approach to get you started is to view the clinical research function as a "contractor" for the sponsor. Your "customers" are top management, product development, marketing, regulatory, FDA and foreign regulators. Your "suppliers" are investigators, investigative sites, central laboratories, central IRBs, CROs, and other outsourced services. Your "products" are data, reports about data, and publications about data. Now you have the foundation for building a workable quality management system (QMS) for clinical research, because you can identify CR's relationship to other functions and parties in the system.
Parts of a Quality Management System It's all how you like to slice and dice things, but I organize my QMS into nine parts:
 Content description of the quality manual (i.e., the physical binder that houses CR's QMS) including: ...[a] Table of Contents. ...[b] A statement—composed, signed, and dated by top management—of their commitment to assure training and compliance to good clinical practices and the procedures it contains. ...[c] Statements of top management's vision and mission for the clinical research function. ...[d] An operations manual describing how clinical trials fit into the overall product development cycle. ...[e] Cross-functional flowcharts for inter-departmental and within-department operations. ...[f] Job descriptions. ...[g] Procedure "style manual". ...[h] Documentation matrix—(a cross-check to regulations and other functions) to assure that there are procedures in place for every regulatory, ethical, and business activity the CR function is expected to fulfill. ...[i] Communications procedure. ...[j] List of procedures and procedure numbers.  Procedures for Prestudy Tasks  Procedures for Study Tasks  Procedures for Close-Out Tasks  Procedures for Data Management Tasks: Database Design  Procedures for Data Management Tasks: Data Entry & Analysis  Procedures for Other Tasks, including: ...[a] Studies on Healthy, Employee Volunteers. ...[b] Label Copy Review. ...[c] QMS Maintenance. ...[d] Training.  Bibliography.  Glossary.
ISO 13485 Quality management systems, Part 820 Quality system regulation The standard, ISO 13485 "Medical devices—Quality management systems—Requirements for regulatory purposes" (2003) was written to assist medical device manufacturers in understanding how to apply ISO 9000 to the medical device development process. In a nutshell, the idea is to ensure a quality product by maintaining a quality process using a system of quality: i.e., the organizational structure, procedures, processes and resources needed to implement quality control, quality assurance, and quality improvement.
The corollary in the US system is the quality system regulation, 21 CFR Part 820; also known as the "QSR". The QSR views clinical trials as simply one more tool in the toolbox of tests to verify a device's design. In a little bit of circularity, Part 820.30 Design Controls is applicable to investigational devices.
The Clinical Research Quality Management System from CDG
CDG's Clinical Research Quality Management System is a comprehensive collection of statements, policies, procedures, templates, and supporting documents that contains everything you need to set up a clinical research function.
Each procedure is designed to tell you 'how to' do something and results in a work product such as a document or report. The procedures are organized chronologically, the way you would organize a project schedule, to walk you step-by-step through the process of running a clinical trial and a clinical department.The manual is divided in sections that follow the major activities of a clinical project. For more information click here.
Monitoring compliance and performance You cannot expect what you do not inspect, so monitoring CR's compliance to good clinical practices and performance against procedures is part and parcel of the system. Most device clinical research functions fall woefully short of measuring either.
Monitoring compliance Compliance is best monitored by an audit. Most large firms have corporate auditing departments. If you are smaller, you can outsource an audit to an independent expert. An entire study, or a single site, or even a few subjects may be selected. Then follow the data starting from the moment the data were recorded in the source files. Was their transfer to case report forms complete and accurate? Was their input into the database complete and accurate? Does a statistical reanalysis give the same results? And do those results support the label copy?
In one firm the label copy claimed that "fifty leading cardiologists" used the device. Corporate auditing made marketing change the copy because it could not be shown that all fifty cardiologists were leading.
Monitoring performance Performance should be monitored ongoingly. When the clinical research staff turn in their monthly time-sheets, they should assign their hours and costs to primary study tasks. You may need to establish a baseline newly. Start by making a list of important tasks and items for a study.
Task duration and labor Next, record the start-date and completion-date for each task. The completion-date minus the start-date gives you the duration for the task. I have actually had to pull this information from old email messages! Then, estimate the number of person-hours for the task as best you can, this gives you the hours of labor for the task.  Count the number of items As you work, record the number of investigative sites per study, the number of monitoring visits per study, the number of monitoring visit-days per study, the number of data queries per study, the enrollment rate of subjects, and any other item that can be counted.  Assign costs to tasks or items As you work, assign the costs that were charged to the study to the tasks involved in implementing the study or to the items accumulated during the study.
Now, when staff turn in their monthly time sheets you can use the information to monitor department performance against a historical reference. Is the number of days to IRB approval longer at one site than another? Is the number of data queries higher for one site than another? Is it higher than one monitor than for another? Is the subject enrollment rate faster or slower? Such department metrics are used ongoingly to monitor performance and prospectively to plan schedules and estimates for future studies.
Procedures and work instructions A good set of procedures is so much more than simply a set of plans, it is the set of proprietary business operations for the clinical research function and is protected as part of your company's proprietary business information. Procedures can be written broad and shallow, where one procedure covers a whole collection of tasks. Or they can be written narrow and deep, where one procedure is written around one task and results in one work product.
A procedure that describes an important task, one who's poor implementation could jeopardize subject safety or data integrity, should be signed by department management or higher. But procedures that are routine, like how to FedEx case report forms to the data center, can be signed off by lower management and are often called work instructions. If you don't write a procedure that CR needs, they will do it for you. You will find them on Post-It Notes, little binders by their desks, scraps of paper taped to the copying machine, or shared by email.
Benefits of a quality management system There are many benefits to having a quality management system for clinical research: 1) managers have better control over their staff and the work product they produce, 2) professional staff have a better understanding of what is expected of them, and 3) the rest of your company has a clearer expectation of what they will receive, what it will cost, and how long it will take to get it.
Perhaps the biggest benefit of a quality management system is that you'll gain some control over study costs by learning how to plan a study. You'll understand where the money goes and be able to make realistic trade-offs between cost and quality.
Learning objective of the workshop The learning objective for the workshop is to learn how to develop a quality management system for clinical research and how to apply it to achieve quality trials.
You will receive [x] PowerPoint slides. [x] A five-hour presentation, informal, and incorporating a variety of learning methods. [x] A 30-minute quiz. [x] An expert speaker (to her chagrin, Dr. Stark has nearly 30 years experience.) [x] Selected procedures. [x] An example documentation matrix. [x] An example of a performance time sheet. [x] A chance for Q&A. [x] 0.55 CEUs and Certificate of Attendance for registered learners who: ...[x] complete 90% attendance, ...[x] are 70% attentive (workshop is the active screen), ...[x] ask one meaningful question, ...[x] take the quiz, and ...[x] provide course feedback. [x] One computer connection to the event. [x] The opportunity for colleagues to audit the event.
Please note: CDG's model Clinical Research Quality System may be purchased separately and is not required for the workshop.
Who should attend [x] People who manage clinical research functions. [x] Clinical research professionals who want a better understanding of their roles. [x] Quality system managers who want to apply quality theory to specific functions. [x] Anyone who will audit a clinical research function. [x] Top management.