Salford Lung Studies: Follow-up Interviews on …...outcomes in the SLS-Asthma, specifically level...

Salford Lung Studies: Follow-up

Interviews on Patient-Centred

Outcomes

Asthma Research Protocol: FINAL Version 2.0 (14 September 2015)

Short Title: SLS-Asthma Follow-up Interviews

GSK Protocol No. 204500

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HEALTH OUTCOMES PROTOCOL

UNIQUE IDENTIFIER HO14-14871 / 204500

ABBREVIATED TITLE SLS-Asthma Follow-up Interviews

FINAL PROTOCOL

APPROVED

DD-MMM-YYYY (Date of last approval signature)

FULL TITLE Salford Lung Studies: Follow-up Interviews on Patient-

Centred Outcomes

SPONSORSHIP Sponsored by GSK

DIVISION GSK Pharma

BUSINESS UNIT Research & Development

DEPARTMENT VEO R&D

HO STUDY

ACCOUNTABLE

PERSON(S)

CONTRIBUTING

AUTHORS

RETENTION CATEGORY

INFORMATION TYPE Health Outcomes Observational (Non-Interventional) Protocol

KEY WORDS / MESH

HEADINGS / META DATA

SLS; Salford Lung Studies; COPD; asthma; patient symptom

and burden; patient priorities; risk factors; adherence barriers

ASSET ID Fluticasone furoate/Vilanterol (FF/VI;

GW685698+GW642444)

GSK ASSET Ellipta

INDICATION COPD and asthma

PPD

PPD

PPD

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SPONSOR SIGNATORY

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for electronic signature. Once signatures are complete, store in IMMS & archive to PIER.

PPD

PPD

PPD

PPD

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PROTOCOL SYNOPSIS

Unique Identifier HO-14-14871 / 204500

Abbreviated Title SLS-Asthma follow-up interviews on patient-centred outcomes

(as per track HO)

GSK Product Fluticasone furoate/Vilanterol (FF/VI)

Rationale The purpose of the study is to conduct follow-up interviews with

a subsample of patients completing the Salford Lung Study (SLS)

in asthma. The SLS-Asthma is an ongoing, 12-month, real-world

study of treatments (Fluticasone Furoate/Vilanterol Inhalation

Powder versus standard of care) in asthma. A mixed methods

approach will be adopted, whereby both quantitative and

qualitative data are collected to combine the need for both wide-

ranging and in-depth information. This exploratory study will be

used to gain insight into the patient experience in the SLS-

Asthma as well as the impact and management of disease from

the patient’s perspective.

Objectives

(Primary, Secondary

& Exploratory)

The primary objectives are as follows:

Describe the background and lifestyle characteristics of

patients taking part in the SLS-Asthma

Describe patient-centred outcomes beyond those captured

by standardised instruments administered in the SLS-

Asthma, focusing on aspects such as symptom experience,

sleep, impact on daily life, and overall quality of life

(QOL)

Describe patients’ experiences, perceptions and

management of disease, focusing on disease awareness,

self-management strategies, and treatment seeking

behaviours

Describe patients’ attitudes and potential barriers to

medication adherence

The secondary objectives are to explore how these factors and

outcomes relate to key outcomes in the SLS-Asthma, as follows:

Level of control as assessed by the Asthma Control Test

(ACT)

Treatment group

Analyses per treatment group are conditioned on the extent to

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which the sample for the follow-up interviews is representative of

the main SLS-Asthma sample.

An additional exploratory objective will be to do the following:

Explore how the primary and secondary objectives relate

to adherence as assessed in the SLS-Asthma

Study Design Exploratory face-to-face and telephone interviews, with a mixed-

methods approach. Closed-ended questions will be administered

to all SLS-Asthma patients participating in the follow-up

interviews. A subsample of patients (10% of follow-up sample)

also will be administered additional in-depth, open-ended

questions.

Study Population and

Sampling Methods

A sample of patients completing the SLS-Asthma who consent to

take part in follow-up interviews within 2 weeks of Visit 6 (end

of SLS-Asthma).

Specifically, the following inclusion criteria apply:

SLS-Asthma completion: Attending end of study (EOS)

visit (Visit 6)

Informed consent: Subjects must be able to provide

informed consent, and have their consent signed and

dated.

Ability to participate in an interview

Data Source SLS-Asthma patient pool

Data Analysis

Methods

Qualitative analysis of the open-ended data will be conducted

using the extended interview transcripts and facilitated by the use

of ATLAS.ti (version 7.1.4 or higher). All transcripts will be

subject to one primary coding and one secondary coding

conducted by separate researchers from RTI Health Solutions. A

qualitative description approach will be used.

Analysis of the closed-ended question data will be conducted

using SAS 9.3. The data will be analysed as observed, with no

imputation of missing data or aggregation across responses,

except in the case of two standardised instruments, which will be

scored according to their respective scoring guidelines. Study

variables will be analysed descriptively, entailing the following:

frequency and percentage distributions for categorical variables;

frequencies and percentages and/or medians and interquartile

ranges for ordinal variables; and means and standard deviations,

median and interquartile ranges, and score ranges for continuous

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measures. Selected variables also will be compared descriptively

across key SLS-Asthma subgroups (asthma control and treatment

group), as defined in the protocol.

Sample Size and

Power

Up to 400 (minimum 350 patients); power calculations not

applicable

Limitations Exploratory cross-sectional study with no a priori defined

statistical tests or hierarchy; 1-year outcomes based on patient

recall post SLS-Asthma exit

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TABLE OF CONTENTS

1 STUDY DESCRIPTION ...................................................................................... 1

1.1 Study Title .................................................................................................................... 1

1.2 Study Overview ............................................................................................................ 1

1.3 Study Objectives .......................................................................................................... 1

1.4 Research Questions ..................................................................................................... 2

1.5 Setting and Investigators .............................................................................................. 3

2 BACKGROUND ................................................................................................. 3

2.1 Burden of Asthma ......................................................................................................... 3

2.2 Assessing Outcomes in Asthma ................................................................................... 4

2.3 The Salford Lung Study in Asthma ............................................................................... 5

3 RATIONALE FOR THE SLS-ASTHMA FOLLOW-UP STUDY ......................... 5

4 METHODOLOGY ............................................................................................... 6

4.1 Study Design ................................................................................................................ 6

4.2 Sample Size ................................................................................................................. 6

4.3 Follow-up Interview Schedule ....................................................................................... 7

4.4 Electric Data Capture ................................................................................................... 8

4.5 Patient Recruitment ...................................................................................................... 9

4.5.1 Inclusion Criteria .............................................................................................................. 9 4.5.2 Patient Sampling Process ............................................................................................... 9 4.5.3 Patient Recruitment and Consent Process ................................................................... 10

4.6 Follow-up Interview Procedures ................................................................................. 11

4.6.1 Interview Format ............................................................................................................ 11 4.6.2 Interview Structure ........................................................................................................ 11 4.6.3 Adverse-Event Reporting .............................................................................................. 12 4.6.4 Data Entry and Transcription......................................................................................... 12

4.7 Data Analysis ............................................................................................................. 12

4.7.1 Assessment of the Representativeness of the SLS-Asthma Follow-up Sample .......... 13 4.7.2 Analysis of the Quantitative Data .................................................................................. 14 4.7.3 Analysis of the Qualitative Data .................................................................................... 18

5 DATA HANDLING AND SECURITY ............................................................... 19

6 REPORTING AND DISSEMINATION .............................................................. 20

7 STUDY LIMITATIONS ..................................................................................... 20

8 REFERENCES ................................................................................................. 22

APPENDIX A. MILESTONES AND DATA DISSEMINATION PLAN .................... A-1

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1 STUDY DESCRIPTION

1.1 Study Title

Salford Lung Studies in Asthma: Follow-up Interviews on Patient-Centred Outcomes

Short title: SLS-Asthma Follow-up Interviews

1.2 Study Overview

The purpose of this exploratory, descriptive study is to conduct follow-up interviews with a sample of

patients completing the Salford Lung Study (SLS) in Asthma (SLS-Asthma). The SLS-Asthma is an

ongoing, 12-month, real-world study of asthma treatments (fluticasone furoate/vilanterol inhalation

powder [Ellipta] vs. standard of care [SOC]). The follow-up study aims to complement the findings of

the SLS-Asthma by providing additional information on treatment outcomes as perceived by patients,

thus providing further context for the SLS-Asthma results. A replicate, follow-up study is ongoing in

chronic obstructive pulmonary disease (COPD), the SLS-COPD study, and will be linked with the

SLS-COPD study, but will not be described here.

A mixed-methods approach will be adopted for the follow-up study, whereby both quantitative and

qualitative data are collected to combine the need for both wide-ranging and in-depth information.

This exploratory study will be used to gain insight into the patient experience in the SLS-Asthma, as

well as the impact and management of disease from the patients’ perspective. The target sample size

for the interviews is between 350 and 400 patients with asthma.

The SLS-Asthma was granted ethics approval by National Research Ethics Service Greater

Manchester South (REC Ref: 12/NW/0455). The follow-up study will be submitted to the United

Kingdom’s (UK’s) National Health Service Research Ethics Committee for approval in August 2015.

1.3 Study Objectives

The purpose of the follow-up interviews is to capture patient-centred information in the context of the

SLS-Asthma.

The primary objectives are to:

Describe the background and lifestyle characteristics of patients taking part in the SLS-Asthma.

Describe patient-centred outcomes beyond those captured by standardised instruments

administered in the SLS-Asthma, focusing on aspects such as symptom experience, sleep,

impact on daily life, and overall quality of life (QOL).

Describe patients’ experiences, perceptions and management of disease, focusing on disease

awareness, self-management strategies, and treatment seeking behaviours.

SLS-Asthma Follow-up Interviews (Protocol No. 204500)

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Describe patients’ attitudes and potential barriers to medication adherence.

The secondary objectives are to explore how the above characteristics and outcomes relate to key

outcomes in the SLS-Asthma, specifically level of asthma control and randomised treatment group.

Analyses per treatment group are conditioned on the extent to which the sample for the follow-up

interviews is representative of the main SLS-Asthma sample, as defined in the following subsection

and in the data analysis plan (DAP) for this study.

An additional exploratory objective will be to explore how the above characteristics and outcomes

relate to adherence as assessed in the SLS-Asthma.

1.4 Research Questions

To meet the study objectives, the following primary and secondary research questions will be

addressed through the asthma follow-up interviews:

Primary question: What are the characteristics and disease impact in the SLS-Asthma sample,

in terms of the following variables, as assessed in the SLS-Asthma follow-up interviews?

1. Sociodemographic, general health, lifestyle, and behavioural and psychological variables

2. Symptoms, sleep, and physical, social and psychological burden, including patients’

priorities and perceptions of change related to these factors

3. Self-management practices and awareness of asthma

4. Patients’ preferences and satisfaction for preventer treatments

5. Medication adherence attitudes and barriers

Secondary question: How do the aforementioned characteristics and disease impact differ by

the following subgroups?

1. Level of asthma control (well controlled vs. not well controlled) as assessed by the

Asthma Control Test (ACT) in the SLS-Asthma and specified in the SLS-Asthma study

protocol (GlaxoSmithKline Research and Development Ltd [GSK] Protocol

No. HZA115150)

2. Randomised treatment (Ellipta vs. SOC)

Exploratory question: How do the aforementioned characteristics and disease differ by

subgroups based on 1) adherence with the study medication, as assessed by the Medication

Adherence Report Scale for Asthma (MARS-A); and 2) analysis of medications (prescribed,

dispensed and collected) in the SLS-Asthma, as specified in the SLS-Asthma study protocol

(GSK Protocol No. HZA115150)?

Details of which variables will be selected for subgroup comparisons are given in the DAP.


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1.5 Setting and Investigators

The SLS-Asthma and the parallel SLS-COPD are sponsored by GSK. Both studies are being

conducted in Salford, UK, and are a collaboration between GSK, Salford Royal NHS Foundation Trust

(SRFT), and the University of Manchester and North West e-Health (NWeH).

The interviews will be conducted by trained interviewers from the SLS community team. The data

collected during the interviews will be analysed by RTI Health Solutions (RTI-HS), a research

organisation located in Manchester. RTI-HS will not have access to any patient identifiable

information.

2 BACKGROUND

2.1 Burden of Asthma

Asthma is a heterogeneous respiratory disease characterised by chronic, reversible airway

inflammation and obstruction that is associated with increasing morbidity and mortality (Kämpe et al.,

2014; Global Initiative for Asthma [GINA], 2004; 2014). Asthma is caused by a variety of triggering

stimuli and is associated with recurrent episodes of wheezing, breathlessness, chest tightness, and

coughing, which are usually accompanied by reduced airflow in the lungs. Up to 300 million people

worldwide are currently estimated to live with the disease, and its prevalence is increasing in many

countries (GINA, 2004; 2014). Asthma accounts for 1 in every 250 deaths worldwide (Alvarez and

Fitzgerald, 2007); and although a decline in deaths and hospitalisation has been observed in some

countries, the disease continues to present an unacceptable burden on health care systems,

commercial and business interests (through lost productivity), and on the lives of patients and their

families (GINA, 2014).

Asthma is associated with considerable patient burden and can have a profound impact on health-

related quality of life (HRQOL) (Oh, 2008; Meltzer et al., 2011). Many patients with asthma experience

unpredictable, recurrent episodes of symptoms (Joshi et al., 2006), which in turn can disrupt physical

functioning and daily activities. Asthma symptoms frequently occur at night, resulting in sleep

disturbance and associated feelings of tiredness during the day (Juniper et al., 1992; Juniper, 2001;

Lanier and Nayak, 2008). Asthma also has significant negative implications for employment,

academic study, social relationships and interactions, and engagement in or enjoyment of sex (Nocon

and Booth, 1991; Milton et al., 2004; Carpentier et al., 2007; Kaptein et al., 2008; McClellan and

Garrett, 1990). People with asthma may experience more depression or anxiety, lower life

satisfaction, and higher levels of psychological distress than non-asthmatics (Ampon et al., 2005; Ten

Thoren and Petermann, 2000; Miles et al., 1997).

The economic costs associated with asthma are estimated to rank as one of the highest amongst

chronic diseases, due to the significant health care utilisation associated with this condition. A

significant proportion of total costs associated with asthma is due to poor control of the disease, which

leads to exacerbations that may require hospitalisations or accident and emergency department visits.

The most important drivers of the direct costs of asthma are hospitalisation and medications, whereas


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the greatest percentage of indirect costs is attributable to work and/or school absenteeism. The cost

of asthma also is strongly correlated with comorbidities, age, and severity of disease (Bahadori et al.,

2009).

2.2 Assessing Outcomes in Asthma

Until recently, clinical trials in respiratory diseases such as asthma have depended primarily on

clinical assessments, such as airway responsiveness and forced expiratory volume in one second, as

indicators of treatment outcome. However, there is increasing evidence that such clinical indicators do

not fully capture patients’ experiences and burden of disease (Eakin et al., 1995; Juniper et al., 1995).

Patients may experience an improvement in health status that is not reflected by clinical assessments

(Juniper, 1995). Given this possibility, it is important that patients’ perceptions of symptoms and

HRQOL are assessed, alongside clinical indicators, when evaluating treatment effectiveness.

Outcomes such as HRQOL are generally assessed through the administration of validated patient-

reported outcome (PRO) questionnaires. PRO measures provide a valuable means of capturing, in a

structured manner, patients’ views by allowing quantification of what is essentially qualitative

information. Such data have become essential for communicating the patient-perceived benefits of

treatment to regulators, payers, and health care professionals. There is increasing recognition of the

importance of collecting information on disease and treatment experience, from a patient-centred

perspective, which may not be captured through standardised questionnaires (Baldwin et al., 2011).

The collection of additional qualitative information, such as that captured through interviews

conducted upon a patient’s exit from a clinical trial, can further elucidate the patient’s experience,

outcomes, and preferences. Such interviews can collect information typically not assessed in clinical

trials, such as disease awareness, treatment-seeking behaviour, behavioural and lifestyle factors, and

patient priorities.

Historically, the aim of asthma treatment has been to minimise symptoms, optimise lung function, and

prevent exacerbations, with lung function frequently identified as the primary endpoint to be used in

clinical trials (Reddel et al., 2009). However, the importance of control in the management and

treatment of asthma has been recognised by GINA and the United States’ National Asthma Education

and Prevention program (Meltzer et al., 2011). Guidance from these bodies emphasises that the goal

of management interventions should be to keep asthma patients in a state of asthma control for as

long as possible and to minimise the risk of future exacerbations. Uncontrolled asthma does not

denote severity but rather the lack of response to adequate pharmacologic therapy. Recent surveys

have reported that between 51% and 59% of patients have uncontrolled asthma even with the use of

standard asthma medications (Meltzer et al., 2011).

Asthma control is defined as the extent to which the various manifestations of asthma have been

reduced or removed by treatment and is composed of two components: the patient’s recent clinical

state and current disease impact (symptoms, night awakenings, use of reliever, and lung function)

and the risk of future adverse events (exacerbations, decline in lung function, and side effects of

treatment). (Reddel et al., 2009; European Medicines Agency [EMA], 2013). Poor asthma control can

affect patients’ day-to-day lives, impact their mental and physical health, and is associated with higher


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risk of asthma exacerbations (Kämpe et al., 2014). Dean and colleagues (2009) reported a significant

association between HRQOL and poor asthma control, in particular nocturnal asthma. Because the

main objective in asthma treatment is to achieve and maintain asthma control (EMA, 2013), it is

critical to understand the contributory factors associated with different patients’ levels of control in

order to inform interventions.

2.3 The Salford Lung Study in Asthma

The SLS-Asthma is a 12-month, open-label, randomised, effectiveness study to evaluate fluticasone

furoate (GW685698) / vilanterol (GW642444) Inhalation Powder delivered once daily via a Novel Dry

Powder Inhaler compared with the existing asthma maintenance therapy alone in subjects with

asthma. The study, together with a parallel study in COPD, is being conducted in a primary care

population in Salford, UK.

The primary endpoint in the SLS-Asthma is the percentage of patients who have either an ACT total

score of ≥ 20 or an increase from baseline of ≥ 3 in ACT total score at week 24 (6-month)

assessment.

3 RATIONALE FOR THE SLS-ASTHMA FOLLOW-UP STUDY

There is increasing recognition of the importance of collecting information on disease and treatment

experiences, from a patient-centred perspective, that may not be captured through standardised PRO

questionnaires (Baldwin et al., 2011). Specific instruments that are used in many clinical studies are

routinely selected for their ability to measure patient-perceived benefits of treatment in relation to key

symptom areas (e.g., breathlessness or fatigue) and so may miss certain humanistic concepts, such

as identity and self-efficacy, and issues such as disease awareness and treatment seeking behaviour.

Moreover, randomised, clinical trials typically do not assess the relative importance of dimensions

potentially being affected by a disease and hence do not register the key priorities amongst patients.

Trials also do not routinely capture potential behavioural or lifestyle risk factors that may impact

clinical outcomes.

The purpose of this exploratory, descriptive follow-up study is to capture patient-centred information in

the context of the SLS-Asthma. It is intended that the resulting data will provide the following:

Patient-centred outcomes not typically captured by standardised outcome measures in asthma

clinical studies

Patients’ perceptions of the relative importance of different patient-centred outcomes in asthma

Potential behavioural, psychological, or other risk factors for poor asthma control and treatment

adherence in asthma


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4 METHODOLOGY

4.1 Study Design

This exploratory, qualitative study involves follow-up interviews with a sample of 350 to 400 asthma

patients who completed the SLS-Asthma. A mixed-methods approach will be taken. Quantitative data

will be collected through the administration of structured, closed-ended questions administered to all

patients recruited into the follow-up interview study. These data will be used to describe the

characteristics, experiences, and perceptions of patients in the SLS-Asthma sample beyond the

information captured in the main study. Qualitative data also will be collected through semi-structured,

open-ended questions on key topic areas; these questions will be administered to 10% of patients

selected at random from the overall asthma follow-up interview sample. The qualitative data will be

used to explore the concepts of interest in greater depth.

The interviews will be conducted, either by telephone or face to face, by trained interviewers from the

SLS community team using a structured interview schedule. Patients’ responses will be recorded

using an electronic data capture (EDC) application (see Section 4.4). The interviewers will receive full

training in the use of the interview schedules and the EDC application by RTI-HS researchers.

4.2 Sample Size

The target sample size for the main SLS-Asthma study is 4,000 patients. Between 350 and 400

patients who have completed the SLS-Asthma will be invited to participate in the follow-up interviews,

of which 10% will be selected at random to take part in an extended interview, including open-ended

questions in addition to the closed-ended questions.

Due to the exploratory nature of the research, inferential statistical tests of between-group differences

will not be performed, and a formal power calculation is not possible. The target sample size has been

set to balance the need to generate descriptive data that are sufficiently precise against the

administrative and patient burden involved in this additional follow-up study. Hence, the targeted

sample size represents a balance between precision and feasibility.

Using Cochran’s (1977) formulas for determining sample size, a sample of 350 to 400 patients from a

total population of 4,000 patients, as anticipated in the SLS-Asthma, will provide margin of error of

between 4.7% and 5.0%, at a confidence level of 95%, which is within the 5% margin of error

generally accepted for categorical variables in survey research (Bartlett et al., 2001). Thus, the

sample size will be sufficient to provide 95% confidence that a given outcome (e.g., percentage of

patients giving a particular response) in the overall SLS-Asthma sample will be plus or minus 4.7% to

5.0% of the outcome obtained in the follow-up sample. Please note, however, that this formula and

these thresholds are contingent upon the type and nature of the variables being analysed, including

assumptions regarding what constitutes the primary variable as well as variances that are unknown to

the researcher prior to analysis. Hence, rather than being viewed as a strict tool for defining

appropriate sample size, this formula should be interpreted as an approximation, weighing in


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pragmatic factors. Please also note that in this study no inferential tests will be performed from the

study, which otherwise would have further implications for sample size determination.

To facilitate the greater depth of analysis required for qualitative, open-ended data, the open-ended

questions will be administered to a subset of 10% of participants. A sample size of 35 to 40 is

considered sufficient to provide a qualitative description of the target topics of interest.

4.3 Follow-up Interview Schedule

An interview schedule has been developed for use with an EDC system. The schedule includes both

closed-ended questions (accompanied by yes/no or multiple response options) and open-ended

questions. The closed-ended questions will be administered to all 350 to 400 asthma patients

participating in the follow-up interviews. The 10% of patients selected to take part in an extended

interview will be administered the standard closed-ended questions, as well as the additional open-

ended questions. The process for the development of the interview schedule was as follows:

Targeted review of the conceptual and qualitative literature on health outcomes in asthma to

identify potential patient-centred concepts for inclusion in the interview schedules

Concept elicitation interviews conducted with an opportunistic sample of 20 patients with asthma

(recruited from a medical recruitment agency), to explore the relevance of the concepts arising

from the literature review and to identify any additional issues of importance to patients

Generation of closed-ended and open-ended questions, representing the different concepts and

issues identified, for inclusion in the interview schedules

Pilot testing of the draft questions with an opportunistic sample of five patients with asthma

(recruited from a medical recruitment agency)

Revision and finalisation of the follow-up interview schedule

The final follow-up interview schedule will target the following areas (see Asthma Follow-up Interview

Schedule included with this protocol):

Introductory demographics (including sociodemograhics and other health issues)

Asthma symptoms

Impact of asthma on daily life (functioning, activity limitations, relationships, psychological impact)

Trigger factors

Self-management and awareness of asthma

Experience and management of asthma attacks

Treatments


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Overall impact and overall QOL

Background and lifestyle information (including disease perceptions, general health, alcohol

consumption, activity levels, and other health issues)

Attention was given to not replicate information collected through the main SLS-Asthma. At the same

time, it was anticipated that the follow-up study would form a distinct data set to the main study; thus,

key background variables (such as age and gender) were collected at the time of interview in addition

to variables not captured in the main SLS-Asthma.

Two standardised instruments also will be administered to patients: the COPD and Asthma Sleep

Impact Scale (CASIS) (Pokrzywinski et al., 2009), and the Adherence Starts with Knowledge-12

(ASK-12) (Matza et al., 2009).

The CASIS is a seven-item measure of sleep impairment associated with respiratory disease,

specifically asthma and COPD, with a 1-week recall period. A single score is derived, with higher

scores indicating greater sleep impairment. The measure was developed simultaneously in the United

States and in the UK, using a systematic approach for PRO development. There is good evidence

supporting the internal consistency reliability, test-retest reliability, and concurrent and known groups

validity in patients with either asthma or COPD (Pokrzywinski et al., 2009).

The ASK-12 is a 12-item measure that assesses barriers to treatment adherence. Three subscale

scores (adherence behaviour, treatment beliefs, and inconvenience/forgetfulness) and a total score

are derived, with higher scores indicate greater barriers to adherence. The ASK-12 is a convenient,

brief measure that can be used to identify potential barriers to adherence that may limit treatment

effectiveness (Matza et al., 2009).

4.4 Electric Data Capture

Patients’ responses to the Asthma Follow-up Interview Schedule will be recorded using an EDC

application. For the 35 to 40 extended interviews, the EDC system will provide free text space for the

entry of key words from responses to the open questions. However, the extended interviews will be

audio-recorded, and the main analysis will be conducted using transcripts of the recordings.

The EDC system is a HTML application with a user interface optimised for use on laptops or tablets

and built by RTI-HS. Interviewers will access the application through a web link, using a secure login.

Upon entering the system, the interviewer will be select either the standard set of questions or the

expanded set, which includes the open-ended questions, depending upon the patient allocation

process described in Section 4.5.2. The data collected from each patient automatically will be

transferred from the EDC application over a secure Internet connection to a database server within

RTI-HS’s European office located in Manchester, UK.

Interviewers will be provided with mobile broadband units (MiFi) to conduct interviews in locations

where no Internet connection is available. In addition, interviewers will take paper versions of the

questionnaire to any remote interview locations as a back-up option in the event that an Internet link


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cannot be established. If the interviewer completes the interview using a paper form, he or she will

enter the data into the EDC system upon returning to the SLS offices.

4.5 Patient Recruitment

4.5.1 Inclusion Criteria

The specific inclusion criteria for participation in the follow-up interviews are described in this section.

Patients will be considered for inclusion only if they meet all of the specified criteria:

SLS-Asthma completion: Attending end of study (EOS) visit (Visit 6).

Informed consent: Subjects must be able to provide informed consent, and have their consent

signed and dated.

Ability to participate in a qualitative interview: Subjects must have sufficient command of the

English language to be able to participate in a qualitative interview with an English-speaking

interviewer. Given the nature of the study, language gains special importance as the means by

which the interviewee constructs their reality and the interviewer interprets their meaning. The

introduction of interpreters for non-English speakers will result in a loss of meaning and potential

misinterpretation that can introduce a bias into the analysis.

4.5.2 Patient Sampling Process

A modified consecutive sampling approach (whereby all members of the population of interest are

eligible to take part and are recruited as they become available) will be used to identify the 350 to

400 patients from the SLS-Asthma. Consecutive sampling is an approach commonly used in nursing

studies to access patients for studies involving a “rolling enrolment” of participants. This sampling

technique is particularly valuable when the recruitment period is sufficiently long to deal with potential

biases that reflect seasonal or other time-related fluctuations. When all members of an accessible

population are invited to participate in a study over a fixed time period, the risk of bias is greatly

reduced (Polit and Beck, 2010) and ensures that the sample is representative of the population from

which it is drawn. In that respect, consecutive sampling has been put forward as the ‘best’ sampling

technique (Kendall, 2003). Given that the SLS-Asthma is a randomised study, it is anticipated that a

consecutive sampling method will allow patients across the two treatment groups to be included in the

follow-up interview study.

The consecutive sampling approach will be modified to allow monthly monitoring of patient numbers

to ensure that patients are recruited to the follow-up study over a full 12-month study period, i.e.,

between third quarter 2015 and third quarter 2016; patients will be exiting the main SLS-Asthma

during the period from first quarter 2015 to first quarter 2017. Thus, if a high number of patients exit

the main SLS study in any one month, a ceiling may be placed on the number of patients enrolled into

the follow-up study for that month, to ensure that follow-up study results are not skewed by seasonal


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factors. In such an event, the consecutive approach will continue with the first patient exiting the SLS

in the following month.

The SLS community team’s nursing staff will present the study to SLS-Asthma patients as they attend

their EOS visit. The 350 to 400 patients who have completed the SLS-Asthma, agree to take part, and

meet the study criteria will be included in the follow-up interviews.

The subset of 10% of patients to take part in the extended interviews will be determined using a

simple random sampling process, with every tenth patient recruited into the follow-up study being

selected for an extended interview. It is anticipated that such a random selection process will ensure

that patients are sampled across different practices, demographic groups, and treatment regimens.

However, the SLS community team will monitor the characteristics of the extended interview sample,

and additional patients may be purposively selected if shortfalls are identified in any individual

subgroups. This sampling approach will be increased (e.g., to 1 in 7) if more patients are required to

achieve the target sample of 10% of the follow-up sample.

In order to control for any potential sample selection biases that may arise due to the fact that the

SLS-Asthma does not evenly recruit from the general practices and/or geographical areas over time

(i.e., with some practices or areas being targeted at earlier vs. later time periods throughout the main

study recruitment period), we will compare and test demographics characteristics and key clinical

features across various practices and geographical areas and evaluate how this may impact on the

overall findings.

4.5.3 Patient Recruitment and Consent Process

All eligible patients will be mailed a study information packet 1 to 2 weeks prior to their attendance at

their general practice for their SLS-Asthma EOS visit. The study information packet will include the

Study Invitation Letter and Participant Information Sheet.

Upon completion of the patient’s EOS visit, a member of the SLS community team’s nursing staff will

further discuss the follow-up study with the patient, to give the patient the opportunity to ask any

questions. Patients then will be asked by the nurse if they would like to participate in the study. If the

patient agrees to take part, the nurse will take the patient’s informed, written consent at that time. If

the patient wishes to take more time to consider the study, he or she will be invited to telephone the

SLS community team if he or she decides to take part. Patients contacting the SLS team by telephone

to agree to take part will be invited to return to their general practice to provide written consent with

one of the SLS nursing staff. Patients will not be included if they contact the team beyond the time

necessary to arrange for the interview to take place within the permissible time frame of the study (set

at a maximum of 2 weeks after the SLS-Asthma EOS visit).

Once consent has been obtained, patients will be asked to give an answer to a selected security

question (chosen by the patient from three options: “What was the name of your first pet?”, “What was

the name of your primary school?”, or “What was the colour of your first car?”) that will be used to

confirm their identity if they participate in a telephone interview. The nurse will record the selected

security question and answers, along with the patients’ contact telephone number on a paper


11

recruitment information form. This information will be transferred to the Study Coordinator (the

interviewer from the SLS community team will fulfil this role) and entered into an electronic database

held at the SLS central office. The entries on the database will be identified only by the individual’s

follow-up interview identifier code (see the following paragraph). The Study Coordinator then will

contact the patient to arrange a time and date for the follow-up interview to take place. The interview

will be conducted within 1 week of each patient’s EOS visit, wherever possible, but no longer than 2

weeks after the EOS visit. This time limit is intended to balance the need to allow sufficient time for

recruitment and arrangement of the interview with the potential confounding effects of recall bias

and/or new treatments being prescribed after leaving the SLS-Asthma.

Patients recruited to the study will be assigned a unique follow-up interview identifier code. This

activity will be undertaken by the Study Coordinator at the SLS central office in Salford. The

coordinator will maintain a database containing the follow-up interview identifier code and the

corresponding SLS-Asthma patient identifier code. This information, as well as security questions and

contact telephone numbers, will be kept separately from all study data (both SLS-Asthma and follow-

up interview data) and will not be accessible to anyone outside the SLS community team.

4.6 Follow-up Interview Procedures

4.6.1 Interview Format

The follow-up interviews will be conducted by trained interviewers from the SLS community team. It is

anticipated that the standard interviews will be conducted by telephone from the SLS central offices in

Salford, UK, thereby reducing the burden for both the patients and the SLS community team.

However, patients will be given the option of a face-to-face interview format if they prefer. In addition,

all extended interviews will be conducted face to face. Face-to-face interviews will take place either at

the patient’s own GP practice or at the patient’s home, if preferred. Telephone interviews will be one

on one, with home interviews conducted in accordance with GSK’s domiciliary standard operating

procedures.

4.6.2 Interview Structure

At the start of each interview, the patient will be asked if he or she still wishes to participate in the

follow-up interview. This will provide patients with the opportunity to indicate if they have changed

their mind since providing written consent. For telephone interviews, patients also will be asked to

confirm their identity through the answer they provided to their selected security question at the time

of consent. Verification of the security question and agreement to proceed will be recorded on the

electronic interview schedule response form.

The subject will be reminded that the information he or she provides will be treated confidentially and

that he or she may terminate the interview at any time. For the extended interviews, the interviewer

also will ask the subject for permission to audio-record the interview, explaining that transcripts will be

produced from the recording and that all references or names that might identify the subject will be

removed.


12

The main part of the interview will follow the structure set out in the interview schedule. Subjects will

be administered the two standardised instruments (CASIS and ASK-12) at the end of the interviews.

It is anticipated that the standard interviews (comprising closed-ended questions only) will take up to

60 minutes, and the extended interviews (comprising closed-ended questions plus open-ended

questions) will take up to 90 minutes. Subjects’ responses to the closed-ended questions will be

recorded by the interviewer on the EDC interview schedule. In the extended interviews, the

interviewer also will take field notes during the responses to the open-ended questions, although the

primary vehicle for recording these responses will be the audio-recordings.

At the close of the interview, the interviewer will ask the subject about his or her experience of taking

part in the interview and whether he or she has any comments or concerns. Each subject will be

thanked for his or her time and assured again that all of the information that he or she has given will

be treated as confidential. Subjects will receive a cash payment for their involvement in the study: £20

for the standard interview, and £25 for the extended interview. In line with arrangements used in the

SLS-Asthma, payments for the standard interviews will be held in named, sealed envelopes at the

participants’ respective general practice. Participants will be asked to collect their payment from their

practice following completion of their telephone interview. Participants taking part in the face-to-face

extended interviews will receive their payment from the interviewer on completion of the interview.

4.6.3 Adverse-Event Reporting

Subjects will not be asked specifically about the side effects of treatments. Nonetheless, any adverse

events spontaneously raised by a patient relating to any GSK product will be communicated through

the standard GSK adverse-event reporting mechanisms, as detailed in GSK’s standard operating

procedures. Interviewers will receive the required GSK training for adverse-event reporting.

4.6.4 Data Entry and Transcription

Responses entered into the EDC system will be stored directly onto a secure server at RTI-HS’s

offices in Manchester, UK.

On completion of each extended interview, the interviewer will upload the electronic audio file through

a secure web-based transfer system to a medical transcription agency for production of verbatim

transcripts. The audio data file will be stored on an encrypted USB storage device and then destroyed

after transcript production. Any identifying information will be removed from the transcripts to maintain

subject confidentiality.

4.7 Data Analysis

As an exploratory study, the focus of the analysis will be to describe the characteristics and

experiences of patients exiting the SLS-Asthma, rather than to test specific hypotheses. The interview

schedule questions will be analysed descriptively in order to inform the research questions set out in

Section 1.4. The asthma data will be analysed separately from the parallel SLS-COPD follow-up data.


13

On completion of the follow-up asthma interviews, RTI-HS will conduct the analysis of the quantitative

and qualitative data in accordance with the SLS-Asthma follow-up study DAP. The DAP specifies the

analytic methods that will be applied to the quantitative data from the closed-ended questions

administered to the full follow-up interview sample (in addition to selected variables from the SLS-

Asthma), as well as the analysis of the qualitative data from the open-ended questions administered

in the extended interviews with the 10% patient subset.

4.7.1 Assessment of the Representativeness of the SLS-Asthma Follow-up Sample

It is possible that the self-selecting nature of the study could introduce bias relating to patients with

different demographic characteristics or disease severity being more or less likely to agree to

participate in a follow-up interview study. Thus, it is important to explore the extent to which the follow-

up sample is representative of the overall SLS-Asthma sample.

Patients participating in the follow-up study and patients in the SLS-Asthma sample not participating

in the follow-up study will be compared on demographic characteristics (age and gender), as well as

on baseline ACT score [≥ 20, 16-19, or ≤ 15]). No treatment comparisons will be performed unless the

follow-up sample is deemed representative of the main SLS-Asthma sample in relation to these

characteristics.

Patients participating in the follow-up study and patients not participating also will be compared in

relation to SLS-Asthma ACT scores at week 52 (total score and increase from baseline) and to the

randomised treatment group.

Summary statistics for these characteristics (mean and standard deviation for continuous variables

[e.g., age] and frequency and percentage distributions for categorical variables [e.g., gender and

randomised treatment]) will be presented for the total SLS-Asthma sample, as well as for the samples

participating and not participating in the follow-up interview study. Assessment of the

representativeness of the follow-up interview sample will take account of the qualitative differences in

the characteristics of interest, as well as the statistical difference. Group differences will be tested by

independent samples t-test for continuous variables and chi-square test statistics for categorical

variables. Statistical significance will be determined at a probability level of 0.05, with adjustment as

appropriate to account for multiple testing (e.g., Bonferroni).

Similar comparisons also will be made for patients taking part in the standard versus extended

interviews within the follow-up study.

The possibility for geographical variability in patients taking part in the follow-up study will be explored

by examining the recruitment rate (i.e., the proportion of patients taking part in the follow-up study

from the original SLS-Asthma sample) across the different SLS-Asthma recruitment sites.


14

4.7.2 Analysis of the Quantitative Data

The quantitative analysis of the closed-ended question data, (detailed in the SLS-Asthma follow-up

study DAP and outlined in the following subsections) will be descriptive, with no inferential statistical

tests performed. The data (with the exception of the two standardised PRO instruments, as described

in the following paragraph) will be analysed as observed, with no imputation of missing data.

Individual study variables will require minimal computation from the observed closed-ended

responses to derive the analysis variable. Such computations include the numeric coding of Likert-

type responses and any associated recoding of “not applicable” responses (e.g., in the assessment of

the daily life impact of asthma). Individual missing items will be treated as missing, with other non-

missing items from that subject coded as previously stated. Per the study patient information sheet, if

a subject decides to terminate the interview part way through and withdraws from the study, his or her

data will be destroyed and none of that subject’s responses will contribute to the final data set.

The two standardised instruments, the CASIS and ASK-12, will be scored (including the treatment of

individual item non-response) according to the standardised scoring guidelines for each measure.

The analyses will be conducted using SAS 9.3 (version 2010; SAS Institute Inc.; Cary, North Carolina)

or higher.

4.7.2.1 Analysis Variables

The research questions and anticipated corresponding variables for analysis are outlined in Table 1.

Table 1. Overview of Potential Variables To Explore Research Questions

No. Research Question Key Variables

Variable

Types

Primary

1 What are the socio-

demographic, general

health, lifestyle,

behavioural, and

psychological characteristics

of the SLS-Asthma sample?

Follow-up Interview Schedule Section 2:

Sex and relationship or living status

Other health problems


Trigger avoidance

Other environmental triggers


Rating of control over disease (and

change over SLS-Asthma)


Employment status and type

Lifestyle assessment

Level of alcohol consumption

Experience of life events

Lifestyle activity level

Dog ownership

Binary/

categorical/

ordinal (1-5)


15


Variable

Types


Age

Age at diagnosis

Continuous

2 What is the disease impact

for the SLS-Asthma in

terms of symptoms, sleep,

physical, social, and

psychological burden,

including patients’ priorities

and perceptions of change

related to these factors?


Experience of symptoms

Severity of symptoms in last 7 days

Binary/

categorical


Perceived change in symptoms and

asthma overall over SLS-Asthma

Ordinal 1-5


Ratings of impact of asthma on daily

life domains (functioning, activities,

relationships, and psychological)

Ratings of impact of daily life domains

on QOL

Ratings of perceived change in daily life

domains over SLS-Asthma

Ordinal (1-4,

1-5)


Rating of overall QOL (and perceived

change over SLS-Asthma)

Follow-up Interview PRO scale:

CASIS total scores

Ordinal

(1-10) /

continuous

(0-100)

3 What are the self-

management practices and

awareness of asthma

amongst the SLS-Asthma

sample?


Day-to-day self-management

Ratings of feelings of control and

confidence in relation to asthma (and

perceived change over SLS-Asthma)


Ratings of severity of last attack

Self-management of last attack

Treatment-seeking behaviour for last

attack


Perceived barriers to accessing health

care

Binary/

categorical

4 What are patients’

preferences and satisfaction

for preventer treatments

used in the SLS-Asthma?


Preferences amongst preventer

treatments

Ratings of overall satisfaction with

preventer treatments

Ratings of likely future use of preventer

treatments

Binary/

categorical


16


Variable

Types

5 What is the level of

medication adherence

attitudes and beliefs for the

SLS-Asthma sample?


Ratings of agreement with adherence

attitudes

Categorical

Follow-up Interview PRO scale:

ASK-12 total scores

ASK-12 subscale scores

Continuous

(1-5)

Secondary

6 How do the aforementioned

characteristics and disease

impact differ by level of

asthma control in the SLS-

Asthma?

Asthma control as assessed by the ACT in

the SLS-Asthma

Categorical

variable

(groups to be

defined in

accordance

with the

analysis of

the ACT in

the SLS-

Asthma),

with

stratified

descriptive

statistics

reported for

selected

variables to

be defined in

the asthma

DAP



impact differ by treatment

in the SLS-Asthma (Ellipta

vs. SOC)?

SLS-Asthma randomised treatment group Binary

variable

(Ellipta vs.

SOC), with

stratified

descriptive

statistics

reported for

selected

variables to

be defined in

the asthma

DAP

Exploratory



impact differ by adherence

levels in the SLS-Asthma?

Adherence levels as assessed in the SLS-

Asthma

Categorical

variable

(groups to be

defined in

accordance

with the

analysis of

adherence in

the SLS-

Asthma),


17


Variable

Types

with

stratified

descriptive

statistics

reported for

selected

variables to

be defined in

the asthma

DAP

ACT = Asthma Control Test; ASK-12 = Adherence Starts with Knowledge-12; CASIS = COPD and Asthma Sleep Impact Scale;

DAP = data analysis plan; PRO = patient-reported outcome; QOL = quality of life; SLS-Asthma = Salford Lung Study in

Asthma; SOC = standard of care.

a Asthma control and adherence level groups to be determined based on analysis of the corresponding variables in the SLS-

Asthma, to be specified in the SLS-Asthma reporting and analysis plan.

Any potential bias resulting from the interview administration method (telephone vs. face to face),

interview format (standard vs. extended), and length of time between the SLS-Asthma EOS visit and

the follow-up interview (less than 1 week vs. 1-2 weeks) also will be explored through a visual

inspection of key variables (e.g., sociodemographic characteristics and disease impact).

4.7.2.2 Primary Descriptive Analysis for Overall Asthma Sample

Descriptive statistics will be calculated for all individual study variables (including the CASIS and

ASK-12) for the overall asthma follow-up sample as follows:

Categorical variables: Frequencies and percentages

Ordinal variables: Frequencies and percentages and/or medians and interquartile ranges, as

appropriate for the individual variable

Continuous variables: Mean and standard deviations, median and interquartile ranges, and score

ranges

4.7.2.3 Secondary Descriptive Analysis by Subgroups

The study was designed to provide descriptive data on patients’ characteristics and experiences,

rather than to test for statistically significant differences between patient groups. Thus, no inferential

statistical tests for differences between groups will be performed.

Descriptive statistics, as outlined in Section 4.7.2.2, will be calculated for selected variables, stratified

by key variables from the main SLS-Asthma data set, i.e., by asthma control and treatment group.

For asthma control, patients will be categorised according to their total and change from baseline ACT

score at week 52. Three groups will be defined as follows:

Group 1: poor and unchanged control (total score < 20 and change score < 3)


18

Group 2: good or improved control (total score ≥ 20 or change score ≥ 3)

Group 3: good and improved control (total score ≥ 20 and change score ≥ 3)

Subgroup analysis by treatment will be conducted only if no significant differences between the follow-

up sample and the remaining SLS-Asthma sample are found by age, gender, and baseline ACT score

(see Section 4.7.1).

A full list of follow-up study analysis variables selected for each group comparison will be presented in

the SLS-Asthma follow-up study DAP. The selection of variables will be based on methodological

factors, the fit with the clinical profile of Ellipta, the degree to which the variables complement data

collection within the main SLS-Asthma, and the variables’ relevance to the grouping variable of

interest.

4.7.2.4 Exploratory Descriptive Analysis by Subgroups

The study was designed to provide descriptive data on patients’ characteristics and experiences,

rather than to test for statistically significant differences between patient groups. Thus, no inferential

statistical tests for differences between groups will be performed.

Descriptive statistics, as outlined in Section 4.7.2.2, will be calculated for selected variables that have

been stratified by adherence level as assessed by the MARS-A in the SLS-Asthma. Three adherence-

level groups will be defined in accordance with the categorisation used in the SLS-Asthma.

In the SLS-Asthma, treatment adherence is also assessed through the analysis of medications

(prescribed, dispensed, and collected) during the study. The quality and completeness of these data

will be evaluated and, if appropriate, will be used to categorise adherence in patients taking part in the

follow-up interviews.

Subgroup analysis by treatment will be conducted only if no significant differences in age, gender, and

baseline ACT scores are found between the follow-up sample and the remaining SLS-Asthma sample

(see Section 4.7.1).

A full list of follow-up study analysis variables selected for each group comparison will be presented in

the SLS-Asthma follow-up study DAP. The selection of variables will be based on methodological

factors, the fit with the clinical profile of Ellipta, the degree to which the variables complement data

collection within the main SLS-Asthma, and the variables’ relevance to the grouping variable of

interest.

4.7.3 Analysis of the Qualitative Data

Qualitative analysis of the open-ended data will be conducted using the extended interview transcripts

and facilitated by the use of ATLAS.ti (Version 7.1.4 or higher; Scientific Software Development,

Berlin, Germany). All transcripts will be subject to one primary coding and one secondary coding

conducted by separate researchers from RTI-HS.


19

A qualitative description (QD) approach will be used for the analysis. QD is a form of qualitative

analysis that is particularly valuable in mixed-methods research and where the intention is to collect

information on individuals’ experiences in relation to a specific topic (Neergaard et al., 2009). The

focus of QD is to describe what informants say, rather than to extrapolate or make conceptual

inferences (Sandelowski, 2000).

An initial coding frame will be generated according the concepts reflected in the open-ended

questions (details presented in the SLS-Asthma follow-up study DAP). This coding frame will be

applied to the data by assigning codes to segments of text in the interview transcripts using ATLAS.ti.

The coding frame will be modified as the analysis progresses to accommodate new information

arising from the data (Sandelowski, 2000).

Once all transcripts have been coded, excerpts relating to each code within each theme will be

extracted and reviewed. The output of the qualitative analysis will be a descriptive summary of

patients’ experiences, perceptions, and explanations, which will be interpreted alongside the results of

the quantitative descriptive analysis.

5 DATA HANDLING AND SECURITY

Patient-identifiable data will not be shared with anyone outside the SLS community team. Signed

consent forms will be retained in a locked cabinet at the general practice of the Principal Investigator.

For patients taking part in the extended interviews, the interview audio file will be uploaded from a

password-protected laptop to the medical transcription agency through a secure web-based transfer

system. The audio files will be stored on an encrypted USB storage device and destroyed as soon as

the transcript has been produced and checked. Any identifying information will be removed from the

transcripts to maintain subject confidentiality.

The EDC application is configured with data validation controls to ensure the interviewer enters logical

information and can prompt the interviewer where data may be missing, incomplete or illogical. The

asthma follow-up interview data will be uploaded directly over a secure Internet connection to a

database server within RTI-HS’s Manchester, UK, office.

The follow-up interview Study Co-ordinator (a member of the SLS community team) will maintain a

database containing the follow-up interview identifier codes and the corresponding SLS-Asthma study

patient identifier codes. The coordinator will maintain a separate database containing contact

telephone numbers and memorable passwords for the telephone interviews, with entries identified

only by the individual’s follow-up interview identifier code. Both databases will be password-protected,

kept separately from all study data (SLS-Asthma and follow-up interviews) and will not be accessible

to anyone outside the SLS study team.

RTI-HS will have no access to personal identifying information (e.g., patient names, addresses or

telephone numbers) or the participants’ SLS-Asthma study patient identifier codes. Once available,

relevant variables from the SLS-Asthma data set will be extracted by the SLS team, and SLS-Asthma


20

patient identifier codes replaced by corresponding follow-up study identifier codes. The extracted data

will then be transferred to RTI-HS for merging with the follow-up study data.

RTI-HS have strict security processes in place to ensure the safety of all systems and data. RTI-HS is

fully compliant with EU data protection legislation (European Parliament Directives 95/46/EC and

2002/58/EC) with regard to the processing of personal data, the free movement of such data and on

privacy and electronic communications. RTI-HS also maintains standard operating procedures for

security and data handling processes, and staff are trained and monitored for compliance with

relevant standard operating procedures.

6 REPORTING AND DISSEMINATION

The results from the research will be written up as a Final Project Report. It is also anticipated that the

findings will be disseminated through presentations at conferences and publications in peer-reviewed

journals. Patients also will be invited to contact the SLS team if they would like to be informed of the

results of the study. For additional information on Milestones and Data Dissemination, please see

Appendix A.

7 STUDY LIMITATIONS

The purpose of the follow-up interviews is to collect patient-centred data not typically captured within

the context of a clinical study. The advantage of using the SLS-Asthma sample for this is that it allows

the follow-up study data to be explored in relation to clinical outcomes and standardised PRO

assessments. Nonetheless, any findings would need to be further verified beyond the present SLS-

Asthma population.

This study has been designed to balance the two key purposes of the follow-up interviews: 1) to

collect data from a sufficient number of patients taking part in the SLS-Asthma to allow the exploration

of patient-centred data beyond those captured within the main study, and 2) to collect qualitative

information to allow a more in-depth analysis of patient experience. Given the considerable resource

implications of conducting qualitative analysis of data from such a large sample (350-400 patients), it

has been decided to limit the collection of open-ended data from only a subset of 10% of the overall

sample.

It is likely that not all patients approached for inclusion in the follow-up interviews will agree to

participate. Furthermore, only patients who have completed the SLS-Asthma will be eligible for

participation in this follow-up study. Therefore, it is recognised that the interview sample may not be

representative of the SLS-Asthma study population from which it is derived. The demographic and

clinical characteristics of the follow-up interview sample and the remaining SLS-Asthma sample will

be compared to help determine any potential bias in the data collected. Key sources of comparison

will be age, gender, level of asthma control, and SLS-Asthma randomised treatment group.


21

It is anticipated that most of the standard interviews (including only the closed-ended questions) will

be conducted by telephone, thereby reducing the burden for both the patients and the SLS community

team. However, it is equally important to allow patients the option of a face-to-face interview format,

either because of physical difficulties talking on the telephone for any time or because they otherwise

feel uncomfortable with a telephone interview. Telephone interviews have been shown to be an

acceptable way to collect PRO data and have been shown to yield comparable results to face-to-face

administration in different asthma populations (McPhail et al., 2009; Lin et al., 2010) and stroke

(Hoffmann et al., 2010; Janssen et al., 2010). Nonetheless, the consistency of responses between the

administration formats in this study will be explored during the analysis to identify any potential biases.

Similarly, potential biases resulting from the inclusion of open-ended questions in the extended

interviews and the longer interval between SLS-Asthma EOS and the follow-up interviews also will be

explored.

A further limitation of this follow-up study is that interviews take place up to 2 weeks after patients

have completed the SLS-Asthma study. This time delay is unavoidable due to logistic issues

concerning the recruitment and consenting process, and the time needed to arrange and conduct the

interviews. Nonetheless, it is possible that events between SLS-Asthma study exit and the conduct of

the follow-up interview (not the least of which may be the cessation of SLS-Asthma study medication,

in some cases) could impact responses. Potential bias resulting from the length of time between the

SLS-Asthma EOS visit and the follow-up interview will be explored in the analysis as defined in the

DAP. Further, it is not known whether any bias will arise from the requirement for patients in the

follow-up study to be able to take part in an interview.

Some questions in this study ask about patients’ perception of change in symptoms, function, and

well-being over the 1-year SLS-Asthma study period. This recall period introduces the possibility of

recall bias. Whilst recognising the importance of this, recall bias is a common concern for questions

that target specific events, activities, or states, whereas it is less of an issue when patients are asked

about change or progression over time. For example, physicians routinely ask patients in clinical

practice about changes in disease state over time to support care management and justify any

changes in treatment. The questions in this follow-up study ask patients to assess their symptoms,

QOL, and disease status at the time of interview and whether they perceive these factors to have

improved, deteriorated, or remained unchanged. Thus, the study does not ask specific questions to

estimate a score or status at a past time period but rather the patients’ perception of change in that

dimension. Additionally, the questions that involve a recall period target central and tangible aspects

of asthma that are presumed to be of immediate importance to patients, further reducing the risk of

recall bias. Moreover, it should be noted that the questions have been tested in the concept validation

interviews, whereby potential recall issues were identified and questions modified or replaced

accordingly. Finally, the two standardised instruments have different recall periods to the individual

survey questions: the CASIS has a 1-week recall and the ASK-12 has variable recalls. These different

periods of recall will be taken into account when interpreting the results obtained.

Another potential limitation is attribution bias that may arise when patients mistakenly attribute

symptoms to a specific condition rather than other underlying comorbid factors or vice versa. In this

study, we ask patients to assess how various factors are affected ‘because of their asthma’, which


22

may result in attribution bias. However, the benefits of this approach outweigh the risks of attribution

bias, since focusing the discussion on a specific dimension will aid patients’ memory and reduce noise

created by potentially confounding conditions and thus promote an informed opinion and minimise

recall bias. This is also indirectly supported by findings from research investigating the validity of

disease-specific versus generic measures (e.g., Bessette et al., 1998). Again, the questions on

asthma specific symptoms or outcomes have been tested in the concept validation interviews, where

no such attribution bias was apparent.

Finally, this is an exploratory study, the focus of which is to describe the characteristics and

experiences of patients exiting the SLS-Asthma. As a consequence, the data will be analysed

descriptively. Subgroup analyses are proposed but no statistical tests of group differences will be

conducted. Moreover, due to the potential sample bias arising from the self-selected sample,

treatment group comparisons will be made only if the sample is found to be reasonably representative

of the overall SLS-Asthma sample. As the study was not powered to test for group differences, the

assessment of representativeness will be based on qualitative differences between the follow-up

sample and the main SLS-Asthma sample on key characteristics (e.g., age, gender, and treatment

group), as well as on statistical differences.

The exploratory nature of the study allows the consideration of a broad range of issues of potential

relevance to outcomes in asthma but limits the inferences that can be made from the results and

precludes definitive conclusions being drawn. In addition, the results from the study will not be

generalisable to the wider asthma population, and any findings would need to be verified in future

studies designed to test specific hypotheses.

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A-1

Appendix A. Milestones and Data

Dissemination Plan


A-2

Milestones

MILESTONE GUIDANCE OR

POLICY

REQUIREMENT

FORECAST

DATE

MM-YYYY

Forecast Final Protocol Approval

2015.08.31

Forecast GSK CSR Protocol Summary

2015.09.30

Forecast Statistical Analysis Plan Approved

2016.03.31

Forecast Statistical Analysis Complete

2017.11.30

Forecast Final Study Report Complete

2018.03.31

Forecast GSK CSR Results Summary

Posting

2018.04.30

Forecast Manuscript Submission

2018.05.30

Data Dissemination Plan

Attach the Manuscript & Congress Presentation Data Dissemination Plan (DDP) in the

MCQP DDP Powerpoint template. Should include the following information:

MANUSCRIPT PUBLICATION(S)

Note: Only 1 primary manuscript per study is permitted unless approval from Medical.

STUDY ID PUBLICATION

SHORT TITLE

LEAD

AUTHOR

STUDY

ACCOUNTA

BLE

PERSON

ESTIMATE

D

SUBMISSIO

N DATE

(< SAC + 18

months)

TARGET

JOURNAL

HZC115150 Patient burden,

priorities and risk

factors in asthma: an

exploratory interview

study of patients

completing the

Salford Lung Studies

TBD 2018.05.31 TBD

PPD


A-3

CONGRESS PRESENTATION(S)

STUDY ID ABSTRACT SHORT

TITLE

PRESENTER POSTER OR

ORAL

PRESENTATIO

N

CONG

RESS

CONGRESS

LOCATION

CONGRESS

DATE

HZC115150 Patient burden,

priorities and risk

factors in asthma

TBD TBD TBD TBD

DISCLOSURE PLAN

FORECAST

GSK CSR PROTOCOL SUMMARY

(FPA + 30 DAYS)

GSK CSR RESULTS SUMMARY

(SAC + 8 MONTHS)

FULL PROTOCOL POSTING DATE

(Manuscript submission actual + 30 days)

PPD

Salford Lung Studies: Follow-up Interviews on …...outcomes in the SLS-Asthma, specifically level...

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