Response to placebo in patients with chronic obstructive pulmonary disease

Chronic obstructive pulmonary disease (COPD) is the name for a group of lung conditions that resulted in shortness of breath and long-term cough. COPD is a broad term that includes emphysema (damage to the air sacs in the lungs) and chronic bronchitis (long-term inflammation of the airways). COPD is most associated with cigarette smoking, but it is increasingly recognized that people who have never smoked can also develop COPD. It most commonly affects middle-aged or older adults. COPD does not have any cure, and treatment is mostly aimed at decreasing symptom burden. Treatment involves prescribing inhalers that are bronchodilators (medications that open up the airways and hence ease breathing) and inhaled corticosteroids (medications which decrease inflammation in the lungs).

Current treatment with inhaled long-acting bronchodilators and inhaled corticosteroids result in improvement in shortness of breath, flareups or exacerbations (worsening of symptoms), and quality of life. They also result in improvement in lung function. In clinical trials, these medications are compared with the effect of an inactive medication or placebo for the improvement of lung function, shortness of breath, and quality of life. Quality of life is frequently measured in clinical trials using the St. George's Respiratory Questionnaire (SGRQ) score. The SGRQ is a survey designed to measure the impact on overall health, daily life, and perceived well-being in patients with obstructive airways disease. The scale ranges from 1 to 100, where 0 indicates best health and 100 indicates worst health.

A reduction in the SGRQ score by at least 4 points is considered perceivable by patients and hence clinically meaningful. In clinical studies, approximately 55% of individuals prescribed these inhalers report a significant improvement in quality of life. It should however be noted that approximately 40% of individuals given inactive medication or placebo also report a significant improvement in quality of life.

These differences in the proportion of individuals who respond to these medications versus placebo can be used for calculating how many individuals should be enrolled in future clinical trials. Prior studies indicate that patients with milder disease (and thereby a lower SGRQ score) have a greater response to inhaled COPD medications than those with more severe disease. Whether individuals receiving the inactive medication or placebo respond differently depending on disease severity or symptom burden is not known. This study will look at whether the proportion of individuals who show a response in SGRQ will differ by disease severity within the placebo group as well. The analysis will include individuals enrolled in prior trials of bronchodilators and inhaled corticosteroid therapies.

Our findings could impact how future clinical trials are set up. For example, if patients with more serious illnesses or milder symptoms react very differently to a placebo, this needs to be considered in trials to accurately measure how well actual treatments work.