Low-Hanging Fruit: A Pilot Project to Standardize Case Report Forms

The Association of Clinical Research Organizations (ACRO) has provided extensive input to the FDA since the March 2004 publication of "Innovation/Stagnation: Challenge and Opportunity on the Critical Path to New Medical Products." ACRO represents leading clinical research organizations whose primary tasks include increasing efficiencies in clinical research while protecting patient safety and data integrity.

Douglas Peddicord, PhD

Like all of the stakeholders, we support big ideas that may speed development, including the use of biomarkers and surrogate endpoints, and adaptive trial designs. But these ideas may be complicated and slow to implement, particularly since the FDA lacks budget and manpower resources needed to facilitate great leaps forward. So to support the FDA initiative, ACRO member companies, which are involved in a majority of U.S. clinical trials, looked for "low hanging fruit" along the Critical Path.

Sponsors, CROs, sites and investigators use hundreds and thousands of nonstandard case report forms (CRFs) to collect clinical trial data. While a small part of this variability results from the unique data needs of specific studies, the lack of "standardized" case report forms is unnecessary and inefficient, and introduces potential error into an already complicated data collection process.

ACRO proposed to the FDA that we would draft standardized templates for two central measures of clinical trial data: the CRFs for adverse events (AEs) and concomitant medications (CMs). We chose these CRFs because AE and CM data is central to safety assessment during the clinical trial. Thus, standardizing these forms—making important data more consistent and more accessible—has the potential to improve safety as well as efficiency.

Agreeing on the standards

After first reviewing de-identified sample CRFs typically used by member CROs, ACRO convened a project team that included experts in clinical operations, regulatory affairs, biostatistics, data management, and quality assurance. The project team, led by Paul Covington, MD, executive vice president for development, PPD, Inc., agreed that standardized AE, CM, and other CRF templates should:

• Comply with regulatory requirements

• Include data fields that capture required and necessary data, and limit demands for extraneous information

• Not duplicate information collected on other CRFs, where possible

• Allow consistent and efficient data collection, transmission, and analysis

• Be clear and user friendly, to facilitate adoption by all stakeholders

• Be appropriate for use with both pre-approval and postapproval studies, where possible

• Facilitate the transition to electronic data capture

• Be available to all stakeholders for voluntary adoption

As we pursued this pilot project, ACRO looked to work actively with the Clinical Data Interchange Standards Consortium (CDISC), and to keep PhRMA, BIO, and others apprised of our efforts. Specifically, the template AE and CM case report forms drafted by ACRO are intended to be consistent with the data standards of CDISC.

Less than five months after our initial conversation, ACRO was pleased to deliver template adverse event and concomitant medication case report forms to the FDA that, we believe, could facilitate the collection of required, meaningful, consistent, nonduplicative clinical trial data.

Proving safety and efficacy

Our intention, as stated by the project team chair, Alberto Grignolo, PhD, corporate vice president, PAREXEL International, during a meeting with FDA Acting Deputy Commissioner Janet Woodcock, was to provide a proof of concept for one small method of increasing efficiency and reducing error in the conduct and reporting of clinical trials.

The members of ACRO believe that simplifying the basic tools used to assess new product safety and efficacy would facilitate a small but meaningful improvement in the clinical development pathway, and we look forward to working further with the FDA and other stakeholders on developing a set of voluntary, modifiable, standardized case report forms.

Douglas Peddicord, PhD, Executive Director, ACRO