The benefits of a relational database design improve tissue core performance by precise organization, ease of use, and funding opportunities.

Laszlo Radvanyi, Ph.D.
Associate Professor, Melanoma /Medical Oncology
University of Texas M. D. Anderson Cancer Center
Houston, TX 77030

Summary

An organization often needs to make significant changes to existing methods to sustain organizational, technical, and regulatory compliance in a constantly changing research laboratory environment. The management system in place at a tissue core must ensure regulatory compliance is maintained, important lab resources are preserved, and valuable, yet finite, lab space is not wasted. Over the past ten years and spanning several grants, the use of spreadsheets for tissue management has grown. However, lab personnel promotions and movements to other positions combined with changes in the regulatory environment resulted in less than optimal data maintenance for valuable tissue samples, inefficient use of storage space and finally, the need to audit the tissue management process.

We collaborated with a local software developer (Aptia Systems, Inc., Houston, TX) to develop a web-based relational database application on a secure server named Visual Specimen Manager™. A summer student entered ten years of tissue samples into VSM in just three months. Now drop down menus and a graphical user interface enables computer experts and novices alike to enter the data from a set of samples in less than a minute. We believe the advancement of implementing a relational database tissue management system played an important role in our lab recently being awarding a P01 grant. VSM has shown it saves time and labor while facilitating regulatory compliance.

The Problem

The problems our lab faced are the same as other labs at similar research institutions across the United States. Personal −80º freezer space or tissue core freezer space is often kept track of using spreadsheet software and sometimes even in lab notebooks. Spreadsheet programs have become very powerful since their introduction in the 1980’s. We used spreadsheets for many years for the many types of tissue we banked including peripheral blood mononuclear cells (PBMC), serum, plasma, cell lines, and tumor cells. The shortcomings of using spreadsheets became more apparent as the number of tissue samples in the bank grew. The number of samples that could be entered on each spreadsheet was limited as were the number of comments about each sample. Each spreadsheet would have a number of sub-sheets designed to look like the freezer boxes that samples are stored in and the tube’s contents would be entered here for cataloging each tube.

This entire process created more opportunities for typing and other human mistakes and searching for a specific vial nearly impossible unless its location was known to be in a certain area. In late 1997 the FDA introduced 21CFR Part 11 to regulate electronic record keeping. This regulation requires electronic systems that manage regulated electronic records or use electronic signatures must contain several key technical controls. The four key aspects that systems are evaluated by are authenticity, data and system integrity, confidentiality, and non-repudiation.

Popular spreadsheet programs such as Microsoft’s Excel™ were not designed to accommodate the complex electronic validation of data and users now required. Security of the data entered now must also be considered. Generally, thorough password controls can be implemented for user validation but must also protect the configuration of a spreadsheet, including all cell contents, macros, and Visual Basic Applications, from modifications. A major inherent limitation of electronic spreadsheet applications is the lack of an audit trail. This flaw allows data entries on the same spreadsheet to be altered by multiple users without generating a permanent audit trail of what has transpired. According to FDA, the lack of audit trails in a spreadsheet yields the greatest degree of compromise in data integrity.

Solution

Over the past several years the NIH and FDA has begun to more rigorously enforce regulations concerning the use of human tissue in research. Our lab contracted with Aptia Systems, Inc. to develop VSM to meet our needs so we would have a user-friendly relational database application that is compliant with all regulations. A relational database is ideal for managing our tissue and cell sample core data and maintaining compliance with government regulations. Members of our lab have described VSM as easy to learn, user-friendly, and versatile.

VSM is web-based for convenient usage and its graphical user interface has drop down, pre-filled menus for accuracy. VSM can be easily learned and used by lab members of all competencies including high-school summer students. Freezers, tanks, and virtually any storage media are represented by clickable icons. Information windows on boxes and individual samples open when clicked on (below). The search function locates individual samples among the thousands stored. Increased workflow and reduced labor costs puts more lab resources into research that benefits everyone.

The NIH and other grant agencies are constantly looking for ways to stretch research dollars. We recently applied and were awarded a P01 grant where the VSM was described as a powerful new tool to keep track of all human blood and tissue samples from both clinical trial and lab-based research project in the grant. This played a role in getting this P01 awarded, as it convinced reviewers that we had an excellent sample tracking and retrieval database system for the many samples to be studied. Features such as ease-of-use, expandability, being web based, security, and ability to conform to regulatory compliance in an environment that is increasingly protective of the information gathered from humans make VSM an investment in the lab. Bar code scanning and the Cancer Bioinformatics Grid (caBIG) bronze certification are planned for the next VSM release. The National Cancer Institute’s caBIG is a network between the country’s major cancer centers designed to enhance communication and research into cures and treatments for all types of cancer. We look forward to being ready for caBIG and the ability to adapt to changes in research methods not yet imagined.

Screen snapshots of two interfaces of the new VSM LN tank and -80 freezer inventory handling system. The VSM system is a web-based interactive system allowing users to store different specimen types, enter appropriate vial information, move vials from place to place, and take out vials. The system has a password-protected log-on page (not shown) and only authorized users (PI and designates have access.) The PIs have authority to limit personnel to only viewing and manipulating specimens in certain freezers or LN tanks.

The pages are visual in their content allowing personnel to pick the freezer or LN tank they want simply by moving the mouse over the container they want to see and clicking. As shown in A, a rack of a -80 freezer is shown with all its boxes. By clicking, the contents of the box and its related vial information open. By toggling over a particular vial, information specific for that particular vial appears as shown in B. To take out specimens, the user highlights the vial or vials of interest and clicks to remove it. The VSM automatically updates the data with the number, type, and date the vials were removed. Recent updates of the software have drop-down menus to speed up data entry and quickly capture other useful information such as sample HLA subtype.