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Communications to the Editor |

Withdrawal of Treatment in the ISOLDE StudyWithdrawal of Treatment in the ISOLDE Study FREE TO VIEW

Anthony D. D’Urzo, MD, MSC
Author and Funding Information

Affiliations: Primary Care Lung Clinic, Ontario, ON, Canada,  University Hospital Aintree, Liverpool, UK

Correspondence to: Anthony D. D’Urzo, MD, MSC, Primary Care Lung Clinic, 1670 Dufferin St, Suite 107, Ontario, ON, Canada M6H 3M2



Chest. 2004;125(6):2368. doi:10.1378/chest.125.6.2368
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To the Editor:

I read with interest the recent article by Calverley et al (October 2003),1 who address the use of withdrawal from treatment as an outcome in the Inhaled Steroids in Obstructive Lung Disease in Europe (ISOLDE) study. They conclude that losing patients with rapidly deteriorating health status and lung function from follow-up may reduce the power of a study to achieve its primary end point. While I am in complete agreement with this notion from a statistical perspective, I would like to comment on the clinical implications of their findings.

Approximately 58.5% and 41.5% of the fluticasone-treated patients completed and withdrew from the study, respectively. These numbers suggest that a substantial number of patients with COPD do not appear to benefit from inhaled corticosteroid therapy. While one could argue that a much larger sample size than that studied in the ISOLDE study would be needed to see a significant effect on the rate of decline in lung function with inhaled corticosteroids, such a study may not be helpful in guiding clinicians to identify those patients who might benefit from inhaled corticosteroids, particularly since the majority of primary care physicians do not utilize spirometry in the management of COPD.2 Increasing the statistical power of a study such as the ISOLDE study would do little to influence the proportion of patients who ultimately withdraw prematurely, thereby making it difficult to apply any positive statistical findings to the general COPD population. While there is little doubt that inhaled corticosteroids have an important role in the management of COPD, there remains a significant gap between what has been learned from pivotal trials such as the ISOLDE study and how such data may be applied in a real-world setting.

. on behalf of the ISOLDE study groupCalverley, PMA, Spencer, S, Willis, L, et al (2003) Withdrawal from treatment as an outcome in the ISOLDE study.Chest124,1350-1356. [CrossRef] [PubMed]
 
D’Urzo, AD Lung disease prevention: role of office spirometry.Prev Med Managed Care2001;2,167-176
 

Withdrawal of Treatment in the ISOLDE Study

To the Editor:

We are grateful for Dr. D’Urzo’s comments about our article, and agree with his conclusions about the gap between clinical trial data and how this relates to normal clinical practice. One of the purposes of our article was to highlight the conservative nature of any estimate of differences between treatment limbs with regard to rate of change of lung function or indeed symptomatic outcomes. If the study size had been much larger, it is possible that a difference in treatment might have emerged. As Dr. D’Urzo points out, this would still be a very conservative estimate of a “true” effect. The changes in lung function and indeed in symptomatic outcomes that we have seen in the ISOLDE study and other investigations we have undertaken suggest that patients cannot readily be classified into “responders” and “non-responders,” nor can these states be identified with commonly recommended tests such as acute treatment with bronchodilators or oral corticosteroids.12 As such, we will be more cautious than Dr. D’Urzo in suggesting that there was no benefit of treatment in those patients who withdrew from the 3 year trial while receiving fluticisone. What did appear to be the case, and which the trial was better constructed to address, was that taking the inhaled corticosteroid reduced the chances of withdrawing due to ill effects.

Randomized controlled trials remain the best and most robust way that we have for determining whether any treatment strategy is effective, and the magnitude of that effect in routine practice is not always easy to evaluate as Dr. D’Urzo suggests. The development of robust approaches that will do this remain a significant challenge.

References
Calverley, PM, Burge, PS, Spencer, S, et al Bronchodilator reversibility testing in chronic obstructive pulmonary disease.Thorax2003;58,659-664. [CrossRef] [PubMed]
 
Burge, PS, Calverley, PM, Jones, PW, et al Prednisolone response in patients with chronic obstructive pulmonary disease: results from the ISOLDE study.Thorax2003;58,654-658. [CrossRef] [PubMed]
 

Figures

Tables

References

. on behalf of the ISOLDE study groupCalverley, PMA, Spencer, S, Willis, L, et al (2003) Withdrawal from treatment as an outcome in the ISOLDE study.Chest124,1350-1356. [CrossRef] [PubMed]
 
D’Urzo, AD Lung disease prevention: role of office spirometry.Prev Med Managed Care2001;2,167-176
 
Calverley, PM, Burge, PS, Spencer, S, et al Bronchodilator reversibility testing in chronic obstructive pulmonary disease.Thorax2003;58,659-664. [CrossRef] [PubMed]
 
Burge, PS, Calverley, PM, Jones, PW, et al Prednisolone response in patients with chronic obstructive pulmonary disease: results from the ISOLDE study.Thorax2003;58,654-658. [CrossRef] [PubMed]
 
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