Apter 2011.

Methods	Randomized controlled trial
Participants	The study location was primary care and asthma specialty practices serving low‐income, inner‐city neighborhoods in Pennsylvania, USA 165 participants were randomized to the intervention group and 168 participants were randomized to the control group The inclusion criteria were (1) age of 18 years or greater; (2) physician's diagnosis of asthma; (3) prescription for an ICS‐containing medication for asthma; and (4) evidence of reversible airflow obstruction (i.e. either an increase of 15% or greater and 200 ml in FEV1 with asthma treatment over the previous 3 years or an increase in FEV1 or forced vital capacity (FVC) of 12% or greater and 200 ml in FEV1 within 30 minutes of inhaled albuterol) The exclusion criteria were patients with severe psychiatric problems, such as obvious mania or schizophrenia, which would make it impossible for them to understand or carry out problem solving
Interventions	Intervention: PROBLEM SOLVING INTERVENTION Participants met with a research co‐ordinator for 4 sessions of a problem solving (PS) intervention. PS comprised 4 30‐minute sessions. The individualized intervention involved 4 interactive steps, usually 1 per research session. For the 158 participants who reported missing doses of inhaled corticosteroids (ICS), the goal was to improve adherence. For the 7 participants who declared adherence to the prescribed regimen, the goal was to maintain adherence. The first PS step consisted of defining the problem: improving or preserving adherence to ICS use within the patient's unique context and orientation. Problem orientation facilitated the adoption of a rational, positive, and constructive appraisal of how to achieve adherence, with non‐adherence being presented as a problem to be solved. PS was presented as a means of coping with problems more generally and modifying attitudes or beliefs that inhibit or interfere with attempts to solve problems. It was a motivational technique to help the participant view the occurrence of problems as inevitable, normal, and solvable. This first step involved breaking problems into small achievable pieces. The second step was brainstorming for alternative solutions. The third step was choosing the best solution by weighing the consequences, both desirable and undesirable, of each candidate solution. Between the third and fourth meetings, the solution was tried. For the fourth step, the chosen solution was evaluated and revised. As part of this intervention, downloaded data from monitored ICSs were shared with the participant in a nonjudgmental fashion at each visit. At these sessions, subjects followed the same PS steps for addressing an additional problem of their own choosing, such as increasing physical activity. The problems were sometimes interrelated; for example, a father wants to play sports with his child, and improving asthma management makes this easier Control: ASTHMA EDUCATION Patients attended 4 30‐minute sessions, conducted by a research co‐ordinator. Each session was about an asthma education topic unrelated to self management, adherence, or inhaled corticosteroid (ICS) therapy. The topics covered, 1 at each session, were the following: (1) the proper technique for using an albuterol rescue metered‐dose inhaler and a dry powder inhaler or spacer, depending on the patient's medications; (2) the use of peak flow meters; (3) common asthma triggers; and (4) the pathophysiology of asthma. These sessions did not involve discussion of problem solving or adherence, only didactic presentation of health information
Outcomes	The measures of adherence were electronic monitoring. Date and time of ICS actuation was monitored. The electronic monitor can record multiple actuations over a short time period and thus can detect medication 'dumping', multiple actuations of an ICS unaccompanied by inhalation. Only 2 electronic monitors that measure the time and date of ICS use were available at the time of the study. Although no commercial monitor was available for fluticasone‐salmeterol, the most frequent ICS prescribed to subjects during the study period, we were able to use the Diskus Adherence Logger (DAL). Fluticasone and beclomethasone administered by means of metered‐dose inhalers were the next most frequently prescribed; for these, we used a commercial monitor, MDILog (Life Link Monitoring, Inc, Kingston, NY). Approximately 90% of study participants were prescribed an ICS that could be monitored with the DAL or MDILog. 14 patients were initially prescribed inhaled mometasone, but they were switched to a medication that could be monitored, fluticasone, during the study period with their physician's permission. We truncated adherence at 100% for each monitoring period to control for multiple actuations over a very short period of time and to provide a better measure of adherence The patient outcomes were asthma‐related quality of life, asthma control, FEV1, hospitalizations and emergency room visits. Asthma‐related quality of life (AQOL) was measured at visits 1, 5, and 8 with the Mini‐Asthma Quality of Life Questionnaire. This 15‐item questionnaire, reflecting well‐being over the past 2 weeks, has a 7‐point response scale that provides a mean summary score. A 0.5‐unit change is considered clinically meaningful. The Asthma Quality of Life Questionnaire has been shown to be a useful indicator of AQOL in low‐income adults. Asthma control was measured at each visit by using the 7‐item version of the Asthma Control Questionnaire, which asks about symptoms over the past week. The score is the mean of all responses (0, total control; 6, extremely uncontrolled). The minimal important clinical difference is 0.5. A score of greater than 1.5 is considered inadequate control. Spirometry was obtained by using American Thoracic Society procedures for FEV1 and FVC. At each research visit, participants reported hospitalizations and emergency department (ED) visits for asthma or any cause that had occurred since the previous meeting. Measures were taken by research co‐ordinators at each study visit, at monthly visits, for 8 months
Notes	―
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	2 weeks later (visit 2), subjects were randomized according to a computer‐generated algorithm in a 1:1 ratio to intervention or control group
Allocation concealment (selection bias)	Unclear risk	Allocation concealment is not specified. Only state: 2 weeks later (visit 2), subjects were randomized according to a computer‐generated algorithm in a 1:1 ratio to either the intervention or control group
Selective reporting (reporting bias)	Low risk	The study protocol is not available but it is clear that the published reports include all expected outcomes, including those that were pre‐specified
Other bias	High risk	The authors indicate on pg 522 that "The limitations of our study are informative. As noted, electronic monitoring of adherence cannot be achieved divorced from the Hawthorne effect. Because of monitoring, many members of the asthma education group (control group) (66%) thought researchers were teaching about adherence. Thus the interventions might have been perceived similarly by participants. Although the intervention was complicated and labor intensive, it focused only on the patient's behavior and did not consider the environment of the practice site or that of the patient's larger social context."
Blinding of outcome assessment (detection bias) Adherence measure	Low risk	(PRIMARY) ELECTRONIC MONITORING ‐ Objective measure/research co‐ordinator who collected the data was not blinded (was the one who delivered the intervention) but probably would not affect electronic monitor data
Blinding of outcome assessment (detection bias) Patient outcome	High risk	(PRIMARY) ASTHMA CONTROL QUESTIONNAIRE ‐ Open‐label trial/no mention of blinding of study staff/Subjective measure
Blinding of participants (performance bias) Adherence measure	Low risk	(PRIMARY) ELECTRONIC MONITORING ‐ Objective measure/data dumping is accounted for(pg 518) "We electronically monitored the date and time of ICS actuation. The electronic monitor can record multiple actuations over a short time period and thus can detect medication "dumping", multiple actuations of an ICS unaccompanied by inhalation."
Blinding of participants (performance bias) Patient outcome	High risk	(PRIMARY) ASTHMA CONTROL QUESTIONNAIRE ‐ Open‐label trial/no mention of blinding of patients/Subjective measure
Blinding of personnel (performance bias) Adherence measure	Low risk	(PRIMARY) ELECTRONIC MONITORING ‐ Objective measure
Blinding of personnel (performance bias) Patient outcome	High risk	(PRIMARY) ASTHMA CONTROL QUESTIONNAIRE ‐ Open‐label trial/no mention of blinding of study personnel/Subjective measure
Incomplete outcome data (attrition bias) Adherence measure	High risk	(PRIMARY) ELECTRONIC MONITORING ‐ A large amount of missing data for this measure. (pg 520) Monitor downloads failed in 380 (20%) of 2360 downloads, 18% of the PS group and 22% of the AE group. Failures were attributed to monitor failure, battery failure, and proximity to other batteries or magnets
Incomplete outcome data (attrition bias) Patient outcome	Unclear risk	(PRIMARY) ASTHMA CONTROL QUESTIONNAIRE ‐ Insufficient information