GOAL: What Have We Learned?

A recent study entitled “Can Guideline-Defined Asthma Control Be Achieved?”1 stands out as one of the most noteworthy clinical studies of the past year because of the important concepts it confirms and because of the many significant questions it raises. Published online in July 2004 and in print in October of the same year, it is referred to by most as the GOAL trial (from the now familiar acronym for “Gaining Optimal Asthma controL”). Based on what we have learned from the GOAL trial, it is likely that the next iteration of asthma guidelines will be somewhat more stringent in their acceptance of symptoms that define “well-controlled asthma” or “acceptable control.” To fully appreciate the study, it is necessary to highlight two previous hypothesis-generating studies2,3 that led to the development of the GOAL trial protocol. In the first of the two studies, the authors pooled data from eight trials using inhalers containing combined salmeterol and fluticasone propionate.2 The data were reanalyzed with a new endpoint based on a composite measurement of asthma control as defined in guidelines published by the Global Initiative for Asthma (GINA). This was the first time a composite endpoint based on current asthma guidelines was used, as opposed to the majority of asthma studies to date, which have selected single-variable endpoints. The results of this analysis indicated that guideline-defined asthma control can be achieved and led to the development of a prospective protocol using the composite measure as the endpoint. The second hypothesis-generating study also indicated that improved quality of life was realized as the level of control improved, control again being defined by a guideline-based composite measure.3 A significant observation across both studies was that similar proportions of individuals were achieving the same levels of asthma control2,3 and improvements in quality of life3 in the populations studied, regardless of the severity of asthma. This suggests that patients with more severe asthma should be taught to expect the same level of control and the same quality of life as those with milder asthma. The GOAL trial was then developed as a “proof of concept” that asthma control according to the GINA guideline-based definition is achievable. The primary objective of the study was to compare the proportion of individuals who achieved a composite guideline-based measure of well-controlled asthma by using an inhaled corticosteroid alone with the proportion of those who achieved the same by using an inhaled corticosteroid in combination with a long-acting agonist. The patients were stratified before randomization, according to their prior exposure to inhaled corticosteroids. Patients in each stratum were started on an initial dose of fluticasone, and approximately half were also given salmeterol in a combination device. There were up to three treatment steps, depending on the stratum, during which the dose of inhaled corticosteroid was escalated to a maximum of 1,000 g of fluticasone propionate per day if patients did not meet the protocol-defined criteria for total control. If the composite measure of total control was achieved, the patient remained on the same dose until the completion of the 52-week study. If protocol-defined total control was not achieved by the time the patient reached the maximum dose, the maximum dose was continued until the end of the study. Editorial