2 The Study

The accept package and application are based on the paper Development and External Validation of the Acute COPD Exacerbation Prediction Tool (ACCEPT), published in 2019.

2.1 Background

Chronic Obstructive Pulmonary Disease (COPD) affects 300 million people worldwide. Patients with COPD often experience what is called an acute exacerbation.

exacerbation: acute worsening of COPD symptoms; acute means sudden onset, short in duration; COPD symptoms include shortness of breath, wheezing, coughing up mucus, etc.

Exacerbation Severity

Patient has an increased need for medication, but does not need hospital care.
Patient has an increased need for medication, and seeks medical assistance.
Patient (caregiver) recongizes rapid deterioration in condition, requiring hospitalization.

2.2 The Study Population

The data for this study was taken from three different studies:

MACRO Clinical Trial

MACRO Paper

STATCOPE Clinical Trial

STATCOPE Paper

OPTIMAL Clinical Trial

OPTIMAL Paper

Clinical Trial 1: MACRO

Number of Participants: 1142

Type of Study: Clinical Randomized

Masking: Triple (Participant, Investigator, Care-Provider)

Criteria

  • Age: > 40 years old
  • COPD diagnosis
  • Does not have asthma
  • 10 pack years or more of smoking

Study Groups

    Placebo
Sugar Pill

The placebo group was given a sugar pill capsule to take once every day for 12 months.

    Treatment
Azithromycin (macrolide antibiotic)

The treatment group was given a 250 mg capsule of Azithromycin (macrolide antibiotic) to take once every day for 12 months.

Data Collection: Primary Metric

Number of COPD Exacerbations

The purpose of this study was to investigate the effects of azithromycin treatment on exacerbation rate. The number of COPD exacerbations during the 12 months of the study is the primary metric.

Number of Years: 1 year

Clinical Trial 2: STATCOPE

Number of Participants: 885

Type of Study: Clinical Randomized

Masking: Triple (Participant, Investigator, Care-Provider)

Criteria

  • Age: 40 - 80 years old
  • COPD diagnosis
  • Does not have asthma
  • 10 pack years or more of smoking

Study Groups

    Placebo
Sugar Pill

The placebo group was given a sugar pill capsule to take once every day for 37 months.

    Treatment
Simvastatin

The treatment group was given 40 mg of simvastatin to take once every day for 37 months.

Data Collection: Primary Metric

Rate of COPD Exacerbations

The purpose of this study was to investigate the effects of azithromycin treatment on exacerbation rate. The number of COPD exacerbations per year during the 37 months of the study is the primary metric.

Number of Years: 3 years

Clinical Trial 3: OPTIMAL

Number of Participants: 432

Type of Study: Clinical Randomized

Masking: Double (Participant, Investigator)

Criteria

  • Age: > 35 years old
  • COPD diagnosis
  • Does not have asthma
  • 10 pack years or more of smoking
  • at least 1 COPD exacerbation in the last year

Study Groups

    Placebo
Tiotropium + Placebo Inhaler

The placebo group was given 2 puffs/day from a placebo inhaler for 12 months

   Treatment 1
Tiotropium + Salmeterol Inhaler

The treatment group was given 2 puffs/day from a Salmeterol inhaler containing 25 ug/puff of salmeterol for 12 months.

   Treatment 2
Tiotropium + (Salmeterol + Fluticasone) Inhaler

The treatment group was given 2 puffs/day from an Advair inhaler containing 25 ug/puff of salmeterol and 250 ug/puff of fluticasone for 12 months.

Data Collection: Primary Metric

Number of COPD Exacerbations

The purpose of this study was to investigate the effects of Salmeterol and/or Advair treatment on exacerbation rate. The number of COPD exacerbations during the 12 months of the study is the primary metric.

Number of Years: 3 years

2.3 Data Collection: Combined Trials

For our study, we combined the results from the three trials described above.

Primary Metric

Exacerbation Rate

The purpose of this study was determine the exacerbation rate of a patient, defined as the # exacerbations / year. We break this down into severe exacerbation rate and overall exacerbation rate. Additionally, we include the results from the MACRO study to predict exacerbation rate with and without the use of Azithromycin as a treatment.

Secondary Metrics

Number of exacerbations (severe and mild/moderate) in the last year.
Prediction % FEV1 Score.
Whether or not a patient currently smokes. 1 = smoker, 0 = non-smoker
Patient age at the beginning of the study.
For the purpose of this study, we only looked at "Male" and "Female" genders.
Domiciliary Oxygen Therapy: At-home oxygen therapy, used to treat COPD. This metric measures whether or not a patient uses oxygen therapy, 1 = Yes, 0 = No.
St. George's Respiratory Questionnaire: This questionnaire is to help doctors/patients determine how much COPD is affecting day-to-day life. The score from the questionnaire is correlated to cough, sputum, and wheezing symptoms. Questionnaire Download
SGRQ Overview
Body Mass Index: ratio of weight (kg) to height squared (m^2)
Long-Acting Muscarinic receptor Antagonists: used for treatment of COPD. This metric asks whether or not a patient has used LAMAs in the past year.
Long-Acting β2 Agonists: used for treatment of COPD. This metric asks whether or not a patient has used LABAs in the past year.
Inhaled Glucocorticoids: used for treatment of COPD. This metric asks whether or not a patient has used inhaled glucocorticoids in the past year.
Statins: generally used to lower cholesteral in blood, but some studies have recently shown they can be effective in COPD treatment. This metric asks whether or not a patient has used statins in the past year.


2.4 Validation

We generated our regression model based on the OPTIMAL, STATCOPE, and MACRO studies. To test how well this model performed with new data, we used a fourth study, ECLIPSE.

Details of the study can be found here: Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints.

Criteria

  • Age: 40 - 75 years old
  • COPD diagnosis
  • Does not have asthma
  • 10 pack years or more of smoking
  • at least 1 COPD exacerbation in the last year