INTRODUCTION

The Consortium on Clinical Trials in ALS, a Subcommittee of the Motor Neuron Diseases Research Group of the World Federation of Neurology (WFN), met at Airlie House, Warrenton, Virginia, April 2 to 4, 1998, to refine and expand the consensus Guidelines for Clinical Trials in ALS/MND that were formulated at the first Airlie House Conference held in 1994. Participants included clinical investigators, FDA officials, representatives of the Pharmaceutical sector and patient advocates. The purpose of this meeting was to improve the efficiency and consistency of trial analysis and design and to facilitate entry to clinical trials of patients earlier in the disease process.

Several new concepts were discussed, including adoption of the Consort Guidelines for the conduct and reporting of clinical trials, ethical issues, protection of patient interests, statistical analytic methods, better definition of surrogate measures of survival, and techniques for measuring strength and respiratory function. Quality of life measures for patients with ALS/MND were elaborated for the first time, and progress was made in agreeing upon methods for measuring bulbar function. Substantial consensus was achieved in elaborating guidelines for investigator and industry collaboration. The important emerging trend to evidence-based medicine became apparent in formulating these guidelines. In each major area, issues which deserve further investigation were identified.

A draft of the document was posted on the website of the World Federation of Neurology (http://www.wfnals.org) for widespread dissemination. This document represents the consensus view of the participants and of the Committee on ALS/MND of the WFN, and includes feedback from experts in the field who commented on the draft.

The process of developing clinical trial guidelines in ALS/MND is a dynamic one, evolving as we gain experience and promising new therapeutic agents. The design of clinical trials has to take into account several conflicting needs in the current climate. The importance of selecting patients by rigorous exclusion and inclusion criteria versus the desire to include patients at the earliest stages of the disease, the wish to design a trial to detect only a meaningful clinical effect versus the risk of missing a small effect, the need to conduct trials in the climate of other approved treatments versus the need for placebo controlled trials, and the lower expense of a short trial using sensitive sophisticated measurements versus the larger and longer scale required by survival measures.

These guidelines should be regarded as recommendations that should be read in the context of the Helsinki Guidelines for the conduct of clinical trials, themselves derived from the Nuremberg declaration. These documents provide the contemporary ethical basis for the conduct of clinical trials.

These clinical trial guidelines are not meant to be an inflexible, final or complete document. Rather, they should be viewed as an attempt to gain a degree of consensus. A third meeting to refine, expand and detail the guidelines is planned in another four years.

The specific guidelines are followed by several appendices which amplify various aspects of the meeting.

The Committee welcomes further comments.

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