Within the past few years in the biopharmaceutical industry, there has been an increase in outsourcing Clinical Data Management (CDM) and related services to qualified outsourced partners, e.g., Contract Research Organizations. Because of the recent need, a Roles and Responsibility matrix (bid grid), as well as defined processes, such as a Guidance Document, have been created for the internal departments involved to better understand and follow the necessary steps for any outsourced study or study-related services.
The bid grid is owned typically by the sponsor procurement or vendor management office. The bid grid serves two purposes: 1) Captures the study-specific cost drivers and 2) Allows the outsourced partner to assign price to cost drivers. Some examples of CDM cost drivers include:
- Number of unique electronic case report forms (eCRFs)
- Number of total CRF pages or eCRF equivalent
- Number of cleanup listings
- Number of external data sources(e.g., central labs, eDiaries, etc.)
- Number of queries to be programmed
- Number of Data Clarification Forms (DCFs)
- Number of terms to be encoded
- Number of data review rounds
- Number of data transfers to SP
- Number of CDM status teleconferences
- Number of interim database locks
As noted earlier, the actual bid for the study is the second half of the document. It reflects all of the possible tasks that an outsourced partner may be required to perform during the course of the trial and is separated out by the various departments/functions. The outsourced partner provides the dollar amount for each requested task.
In addition to Clinical Data Management, the other departments represented in the Guidance Document include Clinical Programming, Statistics and Medical Communications.
The intent of this article is to only discuss the CDM portions of the Guidance Document.
It focuses on four phases of study activities:
- Pre-contract
- Start-up
- Conduct
- Close-out
Pre-Contract Activities
This phase mainly centers on communication with the outsourced partner, sharing documents, as well as meeting to review the accuracy of the bid (ensuring all necessary activities are present with a corresponding cost). Examples of activities performed by the CDM Project Lead during this phase include, but are not limited to, the following:
- Meets with outsourced partner to discuss CDM expectations for deliverables as outlined in the bid.
- Agrees upon and documents turn around times for review or other actions the outsourced partner may have for the task at hand. It is important that both minimum and maximum timeframes are agreed upon.
- Provides standard eCRFs and related standards documents to the outsourced partner representative.
- For paper studies, reviews and approves allowable data corrections unless the outsourced partner is following sponsor process.
- Provides sponsor Global Coding Conventions to ensure adherence to sponsor’s coding standards.
- Provides and agrees upon the standard fields that sponsor would typically require to be encoded.
- Ensures the outsourced partner has responsibility for User Acceptance Testing (UAT)for all data collection tools and external data feeds (eCRF, eDiary, etc.).
- Defines the expected level of data quality.
- If any tasks are likely to be outsourced by the outsourced partner to a third party vendor, makes note to confirm if the vendor selected is on the list of sponsor qualified vendors.
- Discusses with outsourced partner if third party vendors are being used, the outsourced partner will be responsible for defining the specifications, associated databases for receipt of the data and edit checks that will be reviewed and approved by sponsor.
- When only data management is outsourced, ensures other internal, ancillary departments are consulted for CDM tasks that may be required (e.g., study team listings, additional transfers for Clinical Programming or Statistics).
- Reviews and agrees upon issue escalation.
- Reviews and provides requirements for transfer of data to sponsor.
- Defines the expectations with each data transfer – e.g., if in addition to the data set a listing is expected, ensure this is stated.
- Provides requirements for ongoing transfer of data used for internal review.
Start-Up Activities
The CDM Project Lead must bear in mind Good Clinical Data Management Practices, not necessarily the sponsor’s process in determining the quality of data management the outsourced partner is providing. Examples of activities performed by the CDM Project Lead during this phase include, but are not limited to, the following:
- Meets with outsourced partner as needed to assure the outsourced partner’s staff understand the format and intent of all documents, references, and other materials provided to them by CDM Project Lead.
- Provides sponsor expectations on CRF training at PI Meetings. Reviews final training materials.
- Reviews and approves the outsourced partner’s data cleanup plan and database lock criteria.
- Reviews and provides Serious Adverse Event (SAE) cleanup guidelines with the outsourced partner, including sponsor minimum requirements for reconciliation of Serious Adverse Events.
- Reviews and agrees upon expectations of data turnaround times.
- Reviews and gains agreement on proposed data Quality Control (QC) with outsourced partner to ensure it is adequate and performed at pre-defined intervals.
Conduct Activities
After the start-up processes have been implemented, the next step is the actual execution of the clinical trial. As stated previously, it is imperative that the sponsor define the level of quality oversight and share the quality expectations with the outsourced partner. It is important to keep in mind the goal is not to duplicate the work of the outsourced partner, but to ensure the data quality process is sufficient to meet the sponsor’s defined level of data quality.
During the conduct of the study, the CDM Project Lead will follow the Data Quality Plan and perform the following activities, not limited to:
- Reviews a limited set of safety and efficacy exception and/or listing reports at predefined intervals to ensure data quality is provided. The predefined intervals will be study dependent based on the size, complexity, or key deliverables (DMB, interim lock) of the study.
- Ensures synonym tables are sent to the outsourced partner at the expected timeframe.
- Reviews encoding at predefined intervals using the agreed upon dictionary versions.
- Reviews SAS annotated eCRFs/CRFs.
- Ensures SAE reconciliation is conducted according to predefined intervals.
- Reviews and approves the allowed data corrections (paper CRF studies only) and provides to outsourced partner.
- Attends study team meetings that are coordinated, conducted, and minuted by the outsourced partner.
- Reviews status reports on an ongoing basis. Examples of status reports are enrollment data, open/answered queries, percent of data entered, and percent data clean.
- Request updates on external data reconciliation (e.g., PK, central labs, ECG).
- Retains relevant correspondence related to data quality in the Project Notebook after each review cycle.
Closeout Activities
The closeout activities surround the database finalization process, lessons learned session, and archival of documents. For the purposes of this abstract, the database finalization process will focus on database lock and post-lock activities.
- Ensure final SAS transport files and derivations have been received
- Final SAS annotations have been provided by the outsourced partner
- Project Notebook is current
- Database is locked
- Randomization code is transferred to/from outsourced partner as appropriate
- Lessons learned session held with key stakeholders
- Archival CDs (EDC) have been provided to investigator sites
- Archival of study documents
The standardized process outlined in this abstract serves to provide continuity within the data management function in working across therapeutic areas on outsourced clinical trials. Key to a successful outsourced partner relationship is setting clear expectations, using standardized tools and processes, and most frequently cited in any business relationship, communication... communication...communication.
Sandra Hudgens is a Project Manager in GCDM at Schering-Plough and among her responsibilities participates in developing standardized processes when working with outsource partners.
Sandra began her career in the biopharmaceutical industry seventeen years ago at Covance Central Laboratory Services in managerial roles supporting sponsors and investigators in the Protocol Administration and Investigator Services departments. After six years, Sandra joined Eli Lilly where she served as a GCDM Team Leader and GCDM Consultant. In her GCDM Consultant role, Sandra was involved with developing standardized practices and tools for functional outsourcing.
Sandra joined Schering-Plough in 2007 and continues her passion for working with internal and external colleagues that maximizes the potential for both sponsor and outsourced partner’s organizations.
Sandra attended Purdue University where she majored in Medical Technology. She received her Bachelor in Science in Accounting from Indiana University and completed her Master in Business Administration from Indiana Wesleyan University.
Robin Still is a Manager in GCDM at Schering-Plough. Her Therapy Areas include Asthma/Allergy, Infectious Disease, HIV and Dermatology. She has recently been involved with revitalizing the Outsourcing approach within data management at SPRI.
Robin’s career in the data management arena spans over the past twelve years. It includes managing at a CRO, Covance Central Labs and the past six years at Schering-Plough.
Robin received an Associate in Science in Respiratory Therapy at Indiana University School of Medicine, a Bachelor in Science in Allied Health Management from Indiana University, and completed her Masters in Science in Holistic Nutrition from the Clayton School of Natural Healing.
This article was printed in the January/February 2010 issue of Pharmaceutical Outsourcing, Volume 11, Issue 1. Copyright rests with the publisher. For more information about Pharmaceutical Outsourcing and to read similar articles, visit www.pharmoutsourcing.com and subscribe for free.