http://informahealthcare.com/jas ISSN: 0277-0903 (print), 1532-4303 (electronic) J Asthma, 2014; 51(5): 536–543 ! 2014 Informa Healthcare USA, Inc. DOI: 10.3109/02770903.2014.888572
ADHERENCE AND ASTHMA CONTROL
Patient reminder systems and asthma medication adherence: a systematic review Nancy Tran, BA1, Janet M. Coffman, MA, MPP, PhD2, Kaharu Sumino, MD, MPH3, and Michael D. Cabana, MD, MPH4 College of Medicine, University of Vermont, Burlington, VT, USA, 2Department of Family and Community Medicine, Philip R. Lee Institute for Health Policy Studies, University of California, San Francisco (UCSF), San Francisco, CA, USA, 3Division of Pulmonary and Critical Care Medicine, Washington University School of Medicine, Saint Louis, MO, USA, and 4Department of Pediatrics, Epidemiology and Biostatistics, Philip R. Lee Institute for Health Policy Studies, University of California, San Francisco (UCSF), San Francisco, CA, USA
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Abstract
Keywords
Objective: One of the most common reasons for medication non-adherence for asthma patients is forgetfulness. Daily medication reminder system interventions in the form of text messages, automated phone calls and audiovisual reminder devices can potentially address this problem. The aim of this review was to assess the effectiveness of reminder systems on patient daily asthma medication adherence. Methods: We conducted a systematic review of the literature to identify randomized controlled trials (RCTs) which assessed the effect of reminder systems on daily asthma medication adherence. We searched all English-language articles in Pub Med (MEDLINE), CINAHL, EMBASE, PsychINFO and the Cochrane Library through May 2013. We abstracted data on the year of study publication, location, inclusion and exclusion criteria, patient characteristics, reminder system characteristics, effect on patient adherence rate and other outcomes measured. Descriptive statistics were used to summarize the characteristics and results of the studies. Results: Five RCTs and one pragmatic RCT were included in the analysis. Median follow-up time was 16 weeks. All of the six studies suggested that the reminder system intervention was associated with greater levels of participant asthma medication adherence compared to those participants in the control group. None of the studies documented a change in asthma-related quality of life or clinical asthma outcomes. Conclusion: All studies in our analysis suggest that reminder systems increase patient medication adherence, but none documented improved clinical outcomes. Further studies with longer intervention durations are needed to assess effects on clinical outcomes, as well as the sustainability of effects on patient adherence.
Asthma, cellular phone, electronic mail, patient adherence, reminder systems, telemedicine, telephone, text messaging
Introduction Asthma is a common chronic condition of the airways, affecting 418.9 million adults and 7.1 million children in USA [1]. Daily inhaled corticosteroids (ICS) have been shown to improve asthma control, but poor adherence to medication regimens is associated with increased asthma exacerbations [2]. In addition, studies have shown adherence rates in adult and pediatric populations to range from only 30–70% [3]. These findings are consistent worldwide [4]. The reasons for medication non-adherence are numerous and complex; however, one of the most common documented causes of medication non-adherence is forgetfulness [5,6]. To address poor patient adherence to daily controller medications, a potential clinical intervention is the use of patient reminder systems, which can employ
Correspondence: Michael D. Cabana, MD, MPH, University of California, San Francisco (UCSF) Laurel Heights Campus, 3333 California Street, Suite 245, San Francisco, CA 94118, USA. Tel: +415 514 2660. E-mail: [email protected]
History Received 25 October 2013 Revised 20 January 2014 Accepted 24 January 2014 Published online 13 February 2014
telecommunication technologies such as text messaging, telephone calls and/or interactive voice recognition software. Several recent randomized controlled trials (RCTs) have assessed the impact of specific reminder systems on medication adherence, perceived control of asthma and quality of life. Although there are systematic reviews on subsets of reminder systems on a variety of chronic conditions [7], there are no systematic reviews of the efficacy of general patient reminder system interventions on asthma medication adherence. Patient reminder systems have an increasing potential to improve adherence and affect clinical management of patients. As the use of text messaging has become more ubiquitous and reminder devices have become more compact and user-friendly, the potential for these devices to efficiently engage large numbers of patients has increased. However, it is possible that these types of interventions may only be effective for subsets of patients or clinical settings. To evaluate these interventions and their long-term impact, we conducted a systematic review of the effectiveness of a patient reminder system on adherence to daily asthma controller medications.
DOI: 10.3109/02770903.2014.888572
Methods Study design We conducted a systematic review of the literature to identify articles related to reminder systems and daily asthma medication adherence. We searched all English-language articles in Pub Med (MEDLINE), CINAHL, EMBASE, PsychINFO and the Cochrane Library through May 2013. Articles in our initial search had to have the text word or MeSH term ‘‘Asthma’’ and one of the following text words or MeSH terms: ‘‘Reminder system’’, ‘‘Telephone’’, ‘‘Cellular Phone’’, ‘‘Text Messaging’’, ‘‘Electronic Mail’’ or ‘‘Telemedicine’’. Experts in the field were contacted in order to identify other studies to be included in the analysis.
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age of participants, inclusion and exclusion criteria, characteristics of the reminder system, outcomes measured, intervention duration and adherence rate. We used descriptive statistics to summarize the characteristics of the studies. Overall trends were analyzed and presented. Because of the heterogeneous nature of the interventions, outcome measures and the study populations, we did not perform a meta-analysis. In addition, there were large differences in sample size. The largest study [10] had over 8000 more subjects than the next largest study [11]. Even if the studies did not display heterogeneity, the findings of a meta-analysis would have been heavily weighted towards this single study [12].
Results
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Study selection Two investigators (NTT, MDC) independently examined the full bibliographic citation and abstracts of candidate articles. After identifying articles with promising titles and abstracts, they independently reviewed the full text of this subset of articles to determine whether the studies met the inclusion criteria. Differences were resolved by informal consensus. We calculated a kappa score to measure the degree of agreement in the article selection process between reviewers [8]. The focus of our analysis was the application of reminder systems to improve adherence to daily asthma medication. We defined a reminder system as any mechanism (e.g. pager, text message and telephone call) to encourage the patient to adhere to a pre-established, daily medication regimen. We accepted RCTs that evaluated a reminder system for patients diagnosed with asthma. In addition, to be included in the analysis, the method to determine adherence had to be clearly defined in the study. Furthermore, the method had to account for adherence at the patient level. Examples of acceptable methods included patient self-reporting through recall or a diary, dose counters on controller medications, weight changes in the medications in between visits or rates of prescription refills. We excluded non-English language articles, letters, editorials, dissertations and clinical practice guidelines. Studies without a control group were also excluded because monitoring adherence alone may lead to improvement in adherence rates regardless of the type of intervention [9]. We also excluded articles with interventions that included distance assessment of asthma symptoms and/or medical management programs (e.g. tele-health programs), which have the purpose of potentially modifying an asthma regimen, as opposed to reinforcing adherence to a pre-established regimen. These types of interventions would require a different level of interaction and medical management, compared to reminder systems. We also excluded articles with interventions which were focused on annual reminders (e.g. clinic visit reminders) or reminder systems that targeted healthcare providers (e.g. reminder systems to physicians to administer annual influenza vaccinations to patients with asthma). Data extraction and analysis For the articles that met our inclusion criteria, we abstracted the following information: year of study publication, location,
From the 1115 candidate titles that were identified through the search (Figure 1), 145 were selected for abstract review (kappa score ¼ 0.84). Thirty-one of the 145 abstracts were then selected (kappa score ¼ 0.71) for further review. From the final 31 articles, six studies were selected based on an assessment of the full-text of the article. Ultimately, five RCTs and one pragmatic RCT were included in the analysis. The six studies were conducted in four different countries and published from 2006 to 2011. A more detailed description of the studies and study participants is in Appendix 1. All of the studies were delivered in an outpatient setting. Sample sizes ranged from 26 to 8517 participants. In total, there were 9131 subjects diagnosed with asthma based on clinical history, previous physician diagnosis or objective testing. The age of the subjects ranged from 12 to 98 years. Three studies included adolescent patients (12–18 years old), as well as adult patients [11,13,14]. All but one study [10] excluded participants with significant comorbidities (e.g. chronic obstructive pulmonary
1115 records identified through database searching (n=1111) and contacting experts (n=4)
145 records screened based on titles and abstracts
31 full-text articles assessed for eligibility
6 studies selected for analysis
Figure 1. Selection of studies for systematic review.
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disease, pregnancy and stomach surgery), and one study also used a smoking history of 410 pack years as exclusion criteria [15]. The studies had a median intervention duration of 16 weeks. The study by Vollmer et al. [10] incorporated the longest intervention duration (18 months) of the six trials. The intervention duration of the other five trials ranged from 8 to 24 weeks. Overall completion rates for most of the studies were 480%. The studies incorporated a variety of types of reminder systems, including mobile phone text messaging (n ¼ 2), telephone calls (n ¼ 3) or an audiovisual reminder function (AVRF) that was attached to the subjects’ metered dose inhalers (Table 1). The frequency with which patients received asthma medication reminders varied as well.
Text message reminders were sent once a day [15] or in a tapered schedule from twice a day to three times per week [14]. Telephone call frequency ranged from one call every 2 weeks [11] to once a month [16]. The frequency of the audiovisual reminder function (AVRF) was programmed to beep at twice a day, based on the twice daily schedule of the medication regimen [14]. The content of the reminder message also varied. Some studies included reminders with a standard message (e.g. ‘‘Remember to take your asthma medication morning and evening’’) [15]. In contrast, the text messages in one study [13] included any of 166 text messages based on the patient’s assessed illness and medication beliefs, which were thought to be potential risk factors for non-adherence.
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Table 1. Study characteristics.
Author
Year
Sample size
Intervention description Individually tailored text messages based on participant illness. The type of texts sent was determined by the participant’s baseline scores on the Brief Illness Perception Questionnaire (BIPQ) and the level of medication belief ratings Two calls separated by 1 month from an interactive voice response system (IVR). Participants who responded affirmatively to any of the questions were told that daily use of their controller medication should help prevent symptoms and were advised to discuss the symptoms with their physician The SMS reminder was sent daily. All patients received asthma education
Petrie [13]
2011
147 subjects randomized into a text message group (n ¼ 73) or a control usual care group (n ¼ 74)
Bender [16]
2010
50 subjects randomized into an intervention group (n ¼ 25) or control group (n ¼ 25)
Strandbygaard [15]
2009
Chatkin [11]
2006
Charles [14]
2007
26 subjects randomized into a SMS group (n ¼ 12) and a control group (n ¼ 14) 281 subjects randomized, but only 271 included in analysis. 140 participants analyzed in the intervention group; 131 in control group 110 subjects randomized into an audio-visual reminder function (AVRF) group (n ¼ 55) and a control group (n ¼ 55)
Vollmer [10]
2011
14 064 subjects were prerandomized, but only 8517 included in the analysis. 3903 subjects in intervention group; 4015 in usual care group
Telephone calls every 2 weeks with an emphasis on treatment adherence
An audiovisual reminder function (AVRF), which generated a single beep to notify the subject to take the medication. The device emitted the alarm at predetermined times twice a day Calls for a refill reminder call, a tardy refill call and an initiator/ restart call. Subjects who had 530 days supply remaining received the refill reminder call. The tardy refill call went to individuals who were 41 month past their projected refill date. The initiator/restart call was similar to the tardy refill call, but it was for subjects who were either new or restarting ICS users
Control or comparison group(s)
Intervention duration
No text messages
18 weeks
Subjects in the control group did not receive phone calls
10 weeks
All patients received asthma education, but no SMS reminders Subjects received only an initial and final telephone call, similar to the intervention group
8 weeks
No AVRF
24 weeks
The usual care group did not receive calls
18 months
3 months
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DOI: 10.3109/02770903.2014.888572
Some of the interventions encouraged the subjects to contact their healthcare provider if the subjects had any questions [10,16]. For example, the interactive voice response system (IVR) intervention studied by Bender et al. [16] advised participants to discuss any symptoms with their physicians. Participants in two studies received telephone calls and were required to answer questions about their asthma [11,16]. All of the six studies suggested that the reminder system intervention was associated with greater levels of participant asthma medication adherence compared to participants in the control group (Table 2). The control groups in each study did not receive any reminders (e.g. text messages or telephone calls). However, in reporting the results, only three of the six studies documented baseline adherence rates [10,13,15]. Although the other three studies reported greater adherence in the intervention groups relative to the control groups after the intervention was conducted, it is not known if the intervention and control groups started with the same levels of asthma medication adherence. Of the three studies that documented baseline adherence rates, Petrie et al. [13] and Strandbygaard et al. [15] reported increases of 12.1 and 17.8 percentage points, respectively, in the level of self-reported adherence in the intervention compared to the control group (Figure 2). Vollmer et al. [10] reported adherence based on the modified medication possession ratio (mMPR), which was calculated as the number of days’ supply of medication divided by the number of days in a time window. This study reported that the intervention group’s level of adherence was 2 percentage points higher than the control group’s level of adherence based on mMPR. In addition to medication adherence, other outcomes included: quality of life, symptom control, pulmonary function and patients’ perceptions of illness (Table 3). Three studies [10,15,16] did not note any significant differences in quality of life. There were no changes in asthma control [10,14–16]. In addition, no significant differences were found in PEF and FEV1 measurements [14,15]. Two studies assessed patients’ perceptions of illness; Strandbygaard et al. [15] documented an upward shift in positive medication beliefs based on the Beliefs about Medications Questionnaire (BMQ), while Petrie et al. [13] reported a shift in several patient beliefs in a direction consistent with greater adherence (e.g. increased perceived duration of asthma, increased perceived personal control and increased perceived necessity of preventer medication) based on the Brief Illness Perception Questionnaire (BIPQ).
Discussion Findings from all of the published studies included in our systematic review suggest that a reminder system improved adherence to asthma medication. These studies occurred in a variety of settings and used different types of reminder systems. Second, although medication adherence improved in the intervention groups, none of the studies were able to document a change in asthma-related quality of life or clinical asthma outcomes. However, many of the interventions had a limited duration, with a median time of 16 weeks.
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Although all the studies suggest that reminder systems can improve asthma medication adherence, they are few in number. In addition, there were some methodological limitations in the published literature. Three out of the six studies did not include baseline adherence data [11,14,16]. Despite the study design, randomization does not guarantee that all group characteristics (e.g. the baseline adherence levels) are similar in the intervention group and the control group. It is possible that the actual change, if any, (from baseline to final measurement) in adherence did not differ between the two groups. Two out of the six studies used text messaging [13,15], which is a relatively new technology. In comparison to other interventions (e.g. telephone or web-based programs), text messaging is easy and inexpensive to implement [17,18], which makes it an appealing method to increase adherence. This technology is increasingly being used as a tool for improving treatment adherence in other chronic conditions, such as diabetes [19,20]. Furthermore, one patient population that might benefit from this type of reminder system is the 18- to 24-year-old age group, which has been noted to be the most active and proficient users of text messaging [21]. In addition, a study conducted by Britto et al. [22], adolescents reported high ratings on the ease of use, acceptability and usefulness of a text messaging reminder system for asthma. Naimi et al. [23] conducted interviews with adolescents taking daily asthma medicines and found that adolescents specifically recommended reminder systems as a potential solution to poor adherence. As a result, reminder systems that use text messaging may be particularly helpful in engaging adolescents and young adult populations, which have some of the highest prevalence rates of asthma [24] and have traditionally been more difficult for clinicians to manage [23]. There were various limitations to our analysis. First, while we attempted to be thorough in our literature search, we were limited by our choice of search terms and thus, may not have been able to locate every potential study for analysis. We were also unable to pool the data from all of the studies since the methods used to measure adherence varied. Some studies relied on medication refill rates [10] while others used changes in canister weights [16] or electronic recording devices [14,16] to measure adherence. The age range of the participants in each study was large (12–98 years), which may strengthen the generalizability of the results; however, the adherence rates and patterns of medication use in subgroups (e.g. adolescents) may differ from those in other groups. None of the studies presented findings from subgroup analyses. In addition, the characteristics of the populations enrolled in the six studies overlapped too much to compare findings from subgroups of studies. The small number of studies also precluded us from drawing conclusions about the relative effectiveness of different types of reminder systems. Finally, it is also uncertain if the improvement in adherence would continue after the studies ended and the subjects knew they were no longer being monitored [9]. None of the studies assessed if the intervention led to a longer term, sustained change in self-management and adherence. Assessment of the sustainability of daily medication
Year
2011
2010
2009
2006
2007
2011
Author
Petrie [13]
Bender [16]
Strandbygaard [15]
Chatkin [11]
Charles [14]
Vollmer [10]
Table 2. Effect on medication adherence.
EMR-based
Electronic monitoring devices
Medicine dose-counter on devices
Medicine dose-counter on devices
Electronic monitoring devices
Self-reported
Method of measurement
Control: 0.42 Intervention: 0.42
Not documented
Not documented
Control: 84.2% Intervention: 77.9%
Not documented
Control: 54% Intervention: 56.5%
Baseline adherence
Adherence at 3 months (taking 485% of daily asthma medications): 51.9% (control) versus 74.3% (intervention) Mean percentage of medication taken in last 12 weeks of trial: 66% (control) versus 88% (AVRF) Median percentage of medication taken in last 12 weeks of trial: 74% (control) versus 93% (AVRF) Mean mMPR from baseline to follow-up: 0.04 ± 0.24 (usual care group) versus 0.02 ± 0.24 (intervention group); magnitude of the difference was small (0.02) The drops in mean mMPR from baseline reflect an upward bias in the baseline mMPR since all participants were required to have at least one ICS dispensing during baseline
Medication adherence level of the intervention group was greater compared to the adherence level for the usual care group. The absolute difference was 2 percentage points
Final medication adherence level (taking485% of daily asthma medications) was 22.4 percentage points greater in the intervention group. Final medication adherence level of AVRF group was 18 percentage points greater compared to the adherence level for the control group
Final medication adherence level of IVR group was 15.4 percentage points greater compared to the adherence level for the control group Intervention group had a greater improvement in mean adherence rate of 3.6 percentage points compared to 14.2 percentage points for the control group. The absolute difference was 17.8 percentage points
The intervention group had a greater improvement in mean adherence rate of 1.3 percentage points compared to 10.8 percentage points for the control group. The absolute difference was 12.1 percentage points The intervention group had a higher proportion of patients with adherence levels 480%
Average self-reported adherence: 43.2% (control) versus 57.8% (intervention); [SD ¼ 27.1, t(122) ¼ 3.06, p ¼ 0.003] The proportions with average adherence over 80% or above for the control group was 7 of 66 (10.6%) and for the intervention group 15 of 58 (25.9%) Mean ICS adherence rate greater in IVR group relative to control by a margin of 64.5–49.1% (F ¼ 9.66; p ¼ 0.0032) Mean adherence rate: 70.1% (control) versus 81.5% (SMS)
Adherence summary
Adherence measures
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540 N. Tran et al. J Asthma, 2014; 51(5): 536–543
Petrie, 2011
12
Strandbygaard, 2009
18
Bender, 2010
15
0 0 0 0 0
0 0
0
0
Strandbygaard [15] 2009 (n ¼ 26) Bender [16] 2010 (n ¼ 50) Table 3. Outcomes measured other than adherence to daily asthma medication.
adherence is a potentially important outcome to assess. Knowledge of this outcome would influence whether reminder system interventions need to be implemented on an ongoing basis or if they can be implemented on a shortterm basis to ‘‘train’’ a patient’s medication use behavior. Five of the six studies reported an improved adherence rate between 12 and 22 percentage points (Figure 2) [11,13–16], while the study conducted by Vollmer et al. [10] reported a difference of only 2 percentage points. The smaller difference in adherence rate reported by Vollmer et al. [10] could be due to the fact that subjects were passively recruited. Because the subjects in the five other studies were actively recruited, it is possible that those subjects were ready and primed to increase their adherence before the interventions began. Another explanation for why the difference in magnitude was smaller is that only 54% of the IVR calls directly communicated with the subject or left a detailed message. When the analysis was limited to subjects that had been contacted directly or left a detailed message at least two times, Vollmer et al. [10] reported a stronger intervention effect on adherence with an absolute difference of 6 percentage points. Although all of the studies in our analysis reported an improvement in adherence with the use of a reminder system, this change did not coincide with an improvement in quality of life, symptom control or pulmonary function. It is possible that the magnitude of increased medication adherence may not have been enough to surpass a threshold for improved clinical outcomes (e.g. a decrease in emergency room visits, asthma exacerbations) at the individual patient level [2]. Furthermore, the interventions may improve medication adherence, but may not be addressing all the factors that affect quality of life, control and pulmonary function (e.g. does not address exposure to triggers). It is also possible that the duration of the interventions may not have been long enough to see a significant difference in these outcomes, as the median intervention time was only 16 weeks. In addition, at the beginning of a clinical trial, subjects in the control group who know they are being monitored may adjust their behavior, thereby leading to increased adherence and improvements in clinical outcomes. It may take at least 6 months for initial improvements to revert to a more typical pattern for control participants [15].
Chatkin [11] 2006 (n ¼ 281)
Figure 2. Reported absolute percentage point improvement in adherence due to reminder systems. Studies above the dotted line reported baseline data on adherence to daily asthma medication. For these studies, percentage point differences in adherence post-intervention are adjusted for baseline levels of adherence. For studies below the dotted line, differences in adherence rates are not adjusted for baseline levels of adherence.
‘‘"’’ indicates upward shift in positive medication beliefs; ‘‘"/0’’ indicates shift in some beliefs in a direction consistent with greater adherence; ‘‘0’’ indicates no change.
20
"
15
"/0
10
Beliefs Brief Illness Perception Questionnaire (BIPQ) Beliefs in Medication Questionnaire (BMQ) Symptom control Asthma Control Test (ACT) Asthma Control Questionnaire (ACQ) Asthma Therapy Assessment Questionnaire (ATAQ) Quality of life Mini Asthma Quality of Life Questionnaire (MiniAQLQ) Asthma Quality of Life Questionnaire (AQLQ) Pulmonary function tests Peak Expiratory Flow (PEF) Exhaled Nitric Oxide (eNO) FEV1% of predicted FEV1/FVC Log Response Dose Ratio (LogRDR) to inhaled methacholine Healthcare utilization Urgent care, emergency department care or hospitalization for asthma Short-acting beta agonist use
5
0
22
0
Petrie [13] 2011 (n ¼ 147)
Chatkin, 2006
Charles [14] 2007 (n ¼ 110)
18
Outcomes measured
Charles, 2007
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541
0 0
Suggested Improvement in Adherence Rate Due to Reminder System
2
0
Vollmer [10] 2011 (n ¼ 8517)
Vollmer, 2011
0
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The lack of documented improvement in clinical outcomes should not discount the potential benefits of these interventions at the public health level [25]. An increase in medication adherence, though small in magnitude, may be enough to merit a reminder system intervention when considering the chronic disease self-management of a large population as a whole. Furthermore, Woolf et al. [26] found that far greater increases in efficacy must be achieved for the benefits of improved drug therapy to surpass the gains from improved delivery; thus, reminder systems that target patient adherence may be a better strategy for improving clinical asthma outcomes. Our analysis indicates that all of the studies evaluating reminder systems suggest an increase in medication adherence. We have identified methodological issues with current studies, as well as potential gaps in our knowledge of reminder systems for asthma medication adherence. Future studies should assess the effects of a reminder system on asthma medication adherence over the long-term. In addition, it would be important to assess the effects of such interventions on healthcare utilization and quality of life in greater depth. Finally, given the differences in uptake and acceptance of new technologies, further studies should focus on how these interventions affect asthma medication adherence in specific sub-groups of patients, such as adolescents.
Declaration of interest The authors report no conflicts of interest.
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9. Yeung M, O’Connor SA, Parry DT, Cochrane GM. Compliance with pre-scribed drug therapy in asthma. Respir Med 1994;88: 31–35. 10. Vollmer WM, Feldstein A, Smith DH, Dubanoski JP, Waterbury A, Schneider JL, Clark SA, Rand C. Use of health information technology to improve medication adherence. Am J Manag Care 2011;17:SP79–SP87. 11. Chatkin JM, Blanco DC, Scaglia N, Wagner MB, Fritscher CC. Impact of a low-cost and simple intervention in enhancing treatment adherence in a Brazilian asthma sample. J Asthma 2006;43:263–266. 12. Sacks HS, Berrier J, Reitman D, Ancona-Berk VA, Chalmers TC. Meta-analysis of randomized controlled trials. N Engl J Med 1987; 316:450–455. 13. Petrie KJ, Perry K, Broadbent E, Weinman J. A text message programme designed to modify patients’ illness and treatment beliefs improves self-reported adherence to asthma preventer medication. Br J Health Psychol 2012;17:74–84. 14. Charles T, Quinn D, Weatherall M, Aldington S, Beasley R, Holt S. An audiovisual reminder function improves adherence with inhaled corticosteroid therapy in asthma. J Allergy Clin Immunol 2007;119: 811–816. 15. Strandbygaard U, Thomsen SF, Backer V. A daily SMS reminder increases adherence to asthma treatment: a three-month follow-up study. Respir Med 2010;104:166–171. 16. Bender BG, Apter A, Bogen DK, Dickinson P, Fisher L, Wamboldt FS, Westfall JM. Test of an interactive voice response intervention to improve adherence to controller medications in adults with asthma. J Am Board Fam Med 2010;23: 159–165. 17. Junod Perron N, Dao MD, Righini NC, Humair J-P, Broers B, Narring F, Haller DM, Gaspoz J-M. Text-messaging versus telephone reminders to reduce missed appointments in an academic primary care clinic: a randomized controlled trial. BMC Health Serv Res 2013;13:125. 18. Vasbinder EC, Janssens HM, Rutten-van Mo¨lken MP, van Dijk L, de Winter BC, de Groot RC, Vulto AG, et al. e-Monitoring of asthma therapy to improve compliance in children using a real-time medication monitoring system (RTMM): the e-MATIC study protocol. BMC Med Inform Decis Mak 2013;13:38. 19. Klasnja P, Pratt W. Healthcare in the pocket: mapping the space of mobile-phone health interventions. J Biomed Inform 2012;45: 184–198. 20. Vervloet M, van Dijk L, Santen-Reestman J, van Vlijmen B, van Wingerden P, Bouvy ML, de Bakker DH. SMS reminders improve adherence to oral medication in type 2 diabetes patients who are real time electronically monitored. Int J Med Inform 2012;81: 594–604. 21. Smith A. Americans and text messaging. Pew Research Center, 2011. Available from: http://www.pewinternet.org//media//Files/ Reports/2011/Americans%20and%20Text%20Messaging.pdf [last accessed 3 Sept 2013]. 22. Britto MT, Munafo JK, Schoettker PJ, Vockell AL, Wimberg JA, Yi MS. Pilot and feasibility test of adolescent-controlled text messaging reminders. Clin Pediatr (Phila) 2012;51:114–121. 23. Naimi DR, Freedman TG, Ginsburg KR, Bogen D, Rand CS, Apter AJ. Adolescents and asthma: why bother with our meds? J Allergy Clin Immunol 2009;123:1335–1341. 24. Centers for Disease Control and Prevention. Asthma Facts – CDC’s National Asthma Control Program Grantees. Atlanta, GA: U.S. Department of Health and Human Services, Centers for Disease Control and Prevention; 2013. 25. Cummings SR, Rubin SM, Oster G. The cost-effectiveness of counseling smokers to quit. JAMA 1989;261:75–79. 26. Woolf SH, Johnson RE. The break-even point: when medical advances are less important than improving the fidelity with which they are delivered. Ann Fam Med 2005;3:545–552.
Year
2011
2010
2009
2006
2007
2011
Author
Petrie [13]
Bender [16]
Strandbygaard [15]
Chatkin [11]
Charles [14]
Vollmer [10]
Northwest and Hawaii regions
Wellington, New Zealand
Brazil
Copenhagen NV, Denmark
Denver, Colorado
University of Auckland, New Zealand
Location
Appendix 1. Study characteristics
A diagnosis of asthma based on a clinical history and daily symptoms; age between 18 and 45 years; and a positive methacholine challenge test 12 years of age or older with moderate to severe persistent asthma. Required to have a residential telephone number (not only a mobile phone), to be able to comprehend study procedures, and to sign the appropriate informed consent agreement Requirement to take regular ICS at fixed dose, no exacerbation in the previous month or run-in period, not pregnant or lactating and using contraception if of child-bearing potential 18 years of age or older, treatment for asthma during the 12-month period prior to randomization, one or more dispensing of a respiratory medication at outpatient pharmacy during the 12month period prior to randomization, continuous KP membership
16–45 years
18–45 years
Participants recruited from flyers dispensed with asthma preventer medication and e-mails sent to members of a targeted marketing website (www.smilecity.co.nz) Study dates not described Participants recruited through newspaper advertising and at community allergy practices to National Jewish Health, a tertiary care center Study dates not described Participants recruited from advertisements in local newspapers Study dates not described
At 18 weeks, 46 of 74 (62%) control subjects and 57 of 73 (78%) intervention subjects completed the study At 9 months: 52 of 74 (70%) control subjects; 41 of 73 (56%) intervention subjects 25 of 25 (100%) control subjects and 25 of 25 (100%) intervention subjects completed the study Overall completion rate: 50 out of 50 (100%) 12 of 14 (85%) control subjects and 10 of 12 (83%) SMS subjects completed the study Overall completion rate: 22 of 26 (84%) Overall completion rate: 271 out of 281 (96.4%)
13–65 years
Participants were recruited from research volunteer databases, newspaper advertisements and informal contacts Study dates not described Participants were recruited from Kaiser Permanente Northwest (KPNW) and Hawaii (KPH) regions
46 of 55 (83%) control subjects and 44 of 55 (80%) AVRF subjects completed the study Overall completion rate was 90 of 110 (81%) 4015 of 4322 (93%) usual care subjects and 3903 of 4195 (93%) intervention subjects completed the study Overall completion rate was 7918 of 8517 (93%)
18–98 years
12 years+
Participants selected by their physicians in their own clinical setting as having asthma based on clinical and spirometric evidence November 2003 to April 2004
18–65 years
Between 16 and 45 years of age, diagnosed with asthma, but not currently adhering to their preventer medication as prescribed, and owned a mobile phone capable of receiving text messages Physician-diagnosed asthma and prescribed daily inhaled corticosteroid treatment
Age
Setting and dates
Completion rate
Inclusion criteria
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Individuals were excluded from the final analysis if they never received or qualified for an intervention call
Chronic obstructive pulmonary disease, history of any other clinically significant disease, and use of a long-acting beta agonist
Mild persistent asthma, pregnancy or breast-feeding, intention to move during the study, regular use or recent past abuse of alcohol or illicit drugs, clinically significant active medical conditions
Medical co-morbidities and a smoking history of 410 pack years
Any significant disease or disorder that might affect the results; or current participation in any other asthma-related research or clinical trial
Non-English speakers or diagnosis of chronic obstructive pulmonary disease
Exclusion criteria
DOI: 10.3109/02770903.2014.888572
Reminder systems and asthma medication adherence 543
ADHERENCE AND ASTHMA CONTROL
Patient reminder systems and asthma medication adherence: a systematic review Nancy Tran, BA1, Janet M. Coffman, MA, MPP, PhD2, Kaharu Sumino, MD, MPH3, and Michael D. Cabana, MD, MPH4 College of Medicine, University of Vermont, Burlington, VT, USA, 2Department of Family and Community Medicine, Philip R. Lee Institute for Health Policy Studies, University of California, San Francisco (UCSF), San Francisco, CA, USA, 3Division of Pulmonary and Critical Care Medicine, Washington University School of Medicine, Saint Louis, MO, USA, and 4Department of Pediatrics, Epidemiology and Biostatistics, Philip R. Lee Institute for Health Policy Studies, University of California, San Francisco (UCSF), San Francisco, CA, USA
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1
Abstract
Keywords
Objective: One of the most common reasons for medication non-adherence for asthma patients is forgetfulness. Daily medication reminder system interventions in the form of text messages, automated phone calls and audiovisual reminder devices can potentially address this problem. The aim of this review was to assess the effectiveness of reminder systems on patient daily asthma medication adherence. Methods: We conducted a systematic review of the literature to identify randomized controlled trials (RCTs) which assessed the effect of reminder systems on daily asthma medication adherence. We searched all English-language articles in Pub Med (MEDLINE), CINAHL, EMBASE, PsychINFO and the Cochrane Library through May 2013. We abstracted data on the year of study publication, location, inclusion and exclusion criteria, patient characteristics, reminder system characteristics, effect on patient adherence rate and other outcomes measured. Descriptive statistics were used to summarize the characteristics and results of the studies. Results: Five RCTs and one pragmatic RCT were included in the analysis. Median follow-up time was 16 weeks. All of the six studies suggested that the reminder system intervention was associated with greater levels of participant asthma medication adherence compared to those participants in the control group. None of the studies documented a change in asthma-related quality of life or clinical asthma outcomes. Conclusion: All studies in our analysis suggest that reminder systems increase patient medication adherence, but none documented improved clinical outcomes. Further studies with longer intervention durations are needed to assess effects on clinical outcomes, as well as the sustainability of effects on patient adherence.
Asthma, cellular phone, electronic mail, patient adherence, reminder systems, telemedicine, telephone, text messaging
Introduction Asthma is a common chronic condition of the airways, affecting 418.9 million adults and 7.1 million children in USA [1]. Daily inhaled corticosteroids (ICS) have been shown to improve asthma control, but poor adherence to medication regimens is associated with increased asthma exacerbations [2]. In addition, studies have shown adherence rates in adult and pediatric populations to range from only 30–70% [3]. These findings are consistent worldwide [4]. The reasons for medication non-adherence are numerous and complex; however, one of the most common documented causes of medication non-adherence is forgetfulness [5,6]. To address poor patient adherence to daily controller medications, a potential clinical intervention is the use of patient reminder systems, which can employ
Correspondence: Michael D. Cabana, MD, MPH, University of California, San Francisco (UCSF) Laurel Heights Campus, 3333 California Street, Suite 245, San Francisco, CA 94118, USA. Tel: +415 514 2660. E-mail: [email protected]
History Received 25 October 2013 Revised 20 January 2014 Accepted 24 January 2014 Published online 13 February 2014
telecommunication technologies such as text messaging, telephone calls and/or interactive voice recognition software. Several recent randomized controlled trials (RCTs) have assessed the impact of specific reminder systems on medication adherence, perceived control of asthma and quality of life. Although there are systematic reviews on subsets of reminder systems on a variety of chronic conditions [7], there are no systematic reviews of the efficacy of general patient reminder system interventions on asthma medication adherence. Patient reminder systems have an increasing potential to improve adherence and affect clinical management of patients. As the use of text messaging has become more ubiquitous and reminder devices have become more compact and user-friendly, the potential for these devices to efficiently engage large numbers of patients has increased. However, it is possible that these types of interventions may only be effective for subsets of patients or clinical settings. To evaluate these interventions and their long-term impact, we conducted a systematic review of the effectiveness of a patient reminder system on adherence to daily asthma controller medications.
DOI: 10.3109/02770903.2014.888572
Methods Study design We conducted a systematic review of the literature to identify articles related to reminder systems and daily asthma medication adherence. We searched all English-language articles in Pub Med (MEDLINE), CINAHL, EMBASE, PsychINFO and the Cochrane Library through May 2013. Articles in our initial search had to have the text word or MeSH term ‘‘Asthma’’ and one of the following text words or MeSH terms: ‘‘Reminder system’’, ‘‘Telephone’’, ‘‘Cellular Phone’’, ‘‘Text Messaging’’, ‘‘Electronic Mail’’ or ‘‘Telemedicine’’. Experts in the field were contacted in order to identify other studies to be included in the analysis.
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age of participants, inclusion and exclusion criteria, characteristics of the reminder system, outcomes measured, intervention duration and adherence rate. We used descriptive statistics to summarize the characteristics of the studies. Overall trends were analyzed and presented. Because of the heterogeneous nature of the interventions, outcome measures and the study populations, we did not perform a meta-analysis. In addition, there were large differences in sample size. The largest study [10] had over 8000 more subjects than the next largest study [11]. Even if the studies did not display heterogeneity, the findings of a meta-analysis would have been heavily weighted towards this single study [12].
Results
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Study selection Two investigators (NTT, MDC) independently examined the full bibliographic citation and abstracts of candidate articles. After identifying articles with promising titles and abstracts, they independently reviewed the full text of this subset of articles to determine whether the studies met the inclusion criteria. Differences were resolved by informal consensus. We calculated a kappa score to measure the degree of agreement in the article selection process between reviewers [8]. The focus of our analysis was the application of reminder systems to improve adherence to daily asthma medication. We defined a reminder system as any mechanism (e.g. pager, text message and telephone call) to encourage the patient to adhere to a pre-established, daily medication regimen. We accepted RCTs that evaluated a reminder system for patients diagnosed with asthma. In addition, to be included in the analysis, the method to determine adherence had to be clearly defined in the study. Furthermore, the method had to account for adherence at the patient level. Examples of acceptable methods included patient self-reporting through recall or a diary, dose counters on controller medications, weight changes in the medications in between visits or rates of prescription refills. We excluded non-English language articles, letters, editorials, dissertations and clinical practice guidelines. Studies without a control group were also excluded because monitoring adherence alone may lead to improvement in adherence rates regardless of the type of intervention [9]. We also excluded articles with interventions that included distance assessment of asthma symptoms and/or medical management programs (e.g. tele-health programs), which have the purpose of potentially modifying an asthma regimen, as opposed to reinforcing adherence to a pre-established regimen. These types of interventions would require a different level of interaction and medical management, compared to reminder systems. We also excluded articles with interventions which were focused on annual reminders (e.g. clinic visit reminders) or reminder systems that targeted healthcare providers (e.g. reminder systems to physicians to administer annual influenza vaccinations to patients with asthma). Data extraction and analysis For the articles that met our inclusion criteria, we abstracted the following information: year of study publication, location,
From the 1115 candidate titles that were identified through the search (Figure 1), 145 were selected for abstract review (kappa score ¼ 0.84). Thirty-one of the 145 abstracts were then selected (kappa score ¼ 0.71) for further review. From the final 31 articles, six studies were selected based on an assessment of the full-text of the article. Ultimately, five RCTs and one pragmatic RCT were included in the analysis. The six studies were conducted in four different countries and published from 2006 to 2011. A more detailed description of the studies and study participants is in Appendix 1. All of the studies were delivered in an outpatient setting. Sample sizes ranged from 26 to 8517 participants. In total, there were 9131 subjects diagnosed with asthma based on clinical history, previous physician diagnosis or objective testing. The age of the subjects ranged from 12 to 98 years. Three studies included adolescent patients (12–18 years old), as well as adult patients [11,13,14]. All but one study [10] excluded participants with significant comorbidities (e.g. chronic obstructive pulmonary
1115 records identified through database searching (n=1111) and contacting experts (n=4)
145 records screened based on titles and abstracts
31 full-text articles assessed for eligibility
6 studies selected for analysis
Figure 1. Selection of studies for systematic review.
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disease, pregnancy and stomach surgery), and one study also used a smoking history of 410 pack years as exclusion criteria [15]. The studies had a median intervention duration of 16 weeks. The study by Vollmer et al. [10] incorporated the longest intervention duration (18 months) of the six trials. The intervention duration of the other five trials ranged from 8 to 24 weeks. Overall completion rates for most of the studies were 480%. The studies incorporated a variety of types of reminder systems, including mobile phone text messaging (n ¼ 2), telephone calls (n ¼ 3) or an audiovisual reminder function (AVRF) that was attached to the subjects’ metered dose inhalers (Table 1). The frequency with which patients received asthma medication reminders varied as well.
Text message reminders were sent once a day [15] or in a tapered schedule from twice a day to three times per week [14]. Telephone call frequency ranged from one call every 2 weeks [11] to once a month [16]. The frequency of the audiovisual reminder function (AVRF) was programmed to beep at twice a day, based on the twice daily schedule of the medication regimen [14]. The content of the reminder message also varied. Some studies included reminders with a standard message (e.g. ‘‘Remember to take your asthma medication morning and evening’’) [15]. In contrast, the text messages in one study [13] included any of 166 text messages based on the patient’s assessed illness and medication beliefs, which were thought to be potential risk factors for non-adherence.
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Table 1. Study characteristics.
Author
Year
Sample size
Intervention description Individually tailored text messages based on participant illness. The type of texts sent was determined by the participant’s baseline scores on the Brief Illness Perception Questionnaire (BIPQ) and the level of medication belief ratings Two calls separated by 1 month from an interactive voice response system (IVR). Participants who responded affirmatively to any of the questions were told that daily use of their controller medication should help prevent symptoms and were advised to discuss the symptoms with their physician The SMS reminder was sent daily. All patients received asthma education
Petrie [13]
2011
147 subjects randomized into a text message group (n ¼ 73) or a control usual care group (n ¼ 74)
Bender [16]
2010
50 subjects randomized into an intervention group (n ¼ 25) or control group (n ¼ 25)
Strandbygaard [15]
2009
Chatkin [11]
2006
Charles [14]
2007
26 subjects randomized into a SMS group (n ¼ 12) and a control group (n ¼ 14) 281 subjects randomized, but only 271 included in analysis. 140 participants analyzed in the intervention group; 131 in control group 110 subjects randomized into an audio-visual reminder function (AVRF) group (n ¼ 55) and a control group (n ¼ 55)
Vollmer [10]
2011
14 064 subjects were prerandomized, but only 8517 included in the analysis. 3903 subjects in intervention group; 4015 in usual care group
Telephone calls every 2 weeks with an emphasis on treatment adherence
An audiovisual reminder function (AVRF), which generated a single beep to notify the subject to take the medication. The device emitted the alarm at predetermined times twice a day Calls for a refill reminder call, a tardy refill call and an initiator/ restart call. Subjects who had 530 days supply remaining received the refill reminder call. The tardy refill call went to individuals who were 41 month past their projected refill date. The initiator/restart call was similar to the tardy refill call, but it was for subjects who were either new or restarting ICS users
Control or comparison group(s)
Intervention duration
No text messages
18 weeks
Subjects in the control group did not receive phone calls
10 weeks
All patients received asthma education, but no SMS reminders Subjects received only an initial and final telephone call, similar to the intervention group
8 weeks
No AVRF
24 weeks
The usual care group did not receive calls
18 months
3 months
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DOI: 10.3109/02770903.2014.888572
Some of the interventions encouraged the subjects to contact their healthcare provider if the subjects had any questions [10,16]. For example, the interactive voice response system (IVR) intervention studied by Bender et al. [16] advised participants to discuss any symptoms with their physicians. Participants in two studies received telephone calls and were required to answer questions about their asthma [11,16]. All of the six studies suggested that the reminder system intervention was associated with greater levels of participant asthma medication adherence compared to participants in the control group (Table 2). The control groups in each study did not receive any reminders (e.g. text messages or telephone calls). However, in reporting the results, only three of the six studies documented baseline adherence rates [10,13,15]. Although the other three studies reported greater adherence in the intervention groups relative to the control groups after the intervention was conducted, it is not known if the intervention and control groups started with the same levels of asthma medication adherence. Of the three studies that documented baseline adherence rates, Petrie et al. [13] and Strandbygaard et al. [15] reported increases of 12.1 and 17.8 percentage points, respectively, in the level of self-reported adherence in the intervention compared to the control group (Figure 2). Vollmer et al. [10] reported adherence based on the modified medication possession ratio (mMPR), which was calculated as the number of days’ supply of medication divided by the number of days in a time window. This study reported that the intervention group’s level of adherence was 2 percentage points higher than the control group’s level of adherence based on mMPR. In addition to medication adherence, other outcomes included: quality of life, symptom control, pulmonary function and patients’ perceptions of illness (Table 3). Three studies [10,15,16] did not note any significant differences in quality of life. There were no changes in asthma control [10,14–16]. In addition, no significant differences were found in PEF and FEV1 measurements [14,15]. Two studies assessed patients’ perceptions of illness; Strandbygaard et al. [15] documented an upward shift in positive medication beliefs based on the Beliefs about Medications Questionnaire (BMQ), while Petrie et al. [13] reported a shift in several patient beliefs in a direction consistent with greater adherence (e.g. increased perceived duration of asthma, increased perceived personal control and increased perceived necessity of preventer medication) based on the Brief Illness Perception Questionnaire (BIPQ).
Discussion Findings from all of the published studies included in our systematic review suggest that a reminder system improved adherence to asthma medication. These studies occurred in a variety of settings and used different types of reminder systems. Second, although medication adherence improved in the intervention groups, none of the studies were able to document a change in asthma-related quality of life or clinical asthma outcomes. However, many of the interventions had a limited duration, with a median time of 16 weeks.
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Although all the studies suggest that reminder systems can improve asthma medication adherence, they are few in number. In addition, there were some methodological limitations in the published literature. Three out of the six studies did not include baseline adherence data [11,14,16]. Despite the study design, randomization does not guarantee that all group characteristics (e.g. the baseline adherence levels) are similar in the intervention group and the control group. It is possible that the actual change, if any, (from baseline to final measurement) in adherence did not differ between the two groups. Two out of the six studies used text messaging [13,15], which is a relatively new technology. In comparison to other interventions (e.g. telephone or web-based programs), text messaging is easy and inexpensive to implement [17,18], which makes it an appealing method to increase adherence. This technology is increasingly being used as a tool for improving treatment adherence in other chronic conditions, such as diabetes [19,20]. Furthermore, one patient population that might benefit from this type of reminder system is the 18- to 24-year-old age group, which has been noted to be the most active and proficient users of text messaging [21]. In addition, a study conducted by Britto et al. [22], adolescents reported high ratings on the ease of use, acceptability and usefulness of a text messaging reminder system for asthma. Naimi et al. [23] conducted interviews with adolescents taking daily asthma medicines and found that adolescents specifically recommended reminder systems as a potential solution to poor adherence. As a result, reminder systems that use text messaging may be particularly helpful in engaging adolescents and young adult populations, which have some of the highest prevalence rates of asthma [24] and have traditionally been more difficult for clinicians to manage [23]. There were various limitations to our analysis. First, while we attempted to be thorough in our literature search, we were limited by our choice of search terms and thus, may not have been able to locate every potential study for analysis. We were also unable to pool the data from all of the studies since the methods used to measure adherence varied. Some studies relied on medication refill rates [10] while others used changes in canister weights [16] or electronic recording devices [14,16] to measure adherence. The age range of the participants in each study was large (12–98 years), which may strengthen the generalizability of the results; however, the adherence rates and patterns of medication use in subgroups (e.g. adolescents) may differ from those in other groups. None of the studies presented findings from subgroup analyses. In addition, the characteristics of the populations enrolled in the six studies overlapped too much to compare findings from subgroups of studies. The small number of studies also precluded us from drawing conclusions about the relative effectiveness of different types of reminder systems. Finally, it is also uncertain if the improvement in adherence would continue after the studies ended and the subjects knew they were no longer being monitored [9]. None of the studies assessed if the intervention led to a longer term, sustained change in self-management and adherence. Assessment of the sustainability of daily medication
Year
2011
2010
2009
2006
2007
2011
Author
Petrie [13]
Bender [16]
Strandbygaard [15]
Chatkin [11]
Charles [14]
Vollmer [10]
Table 2. Effect on medication adherence.
EMR-based
Electronic monitoring devices
Medicine dose-counter on devices
Medicine dose-counter on devices
Electronic monitoring devices
Self-reported
Method of measurement
Control: 0.42 Intervention: 0.42
Not documented
Not documented
Control: 84.2% Intervention: 77.9%
Not documented
Control: 54% Intervention: 56.5%
Baseline adherence
Adherence at 3 months (taking 485% of daily asthma medications): 51.9% (control) versus 74.3% (intervention) Mean percentage of medication taken in last 12 weeks of trial: 66% (control) versus 88% (AVRF) Median percentage of medication taken in last 12 weeks of trial: 74% (control) versus 93% (AVRF) Mean mMPR from baseline to follow-up: 0.04 ± 0.24 (usual care group) versus 0.02 ± 0.24 (intervention group); magnitude of the difference was small (0.02) The drops in mean mMPR from baseline reflect an upward bias in the baseline mMPR since all participants were required to have at least one ICS dispensing during baseline
Medication adherence level of the intervention group was greater compared to the adherence level for the usual care group. The absolute difference was 2 percentage points
Final medication adherence level (taking485% of daily asthma medications) was 22.4 percentage points greater in the intervention group. Final medication adherence level of AVRF group was 18 percentage points greater compared to the adherence level for the control group
Final medication adherence level of IVR group was 15.4 percentage points greater compared to the adherence level for the control group Intervention group had a greater improvement in mean adherence rate of 3.6 percentage points compared to 14.2 percentage points for the control group. The absolute difference was 17.8 percentage points
The intervention group had a greater improvement in mean adherence rate of 1.3 percentage points compared to 10.8 percentage points for the control group. The absolute difference was 12.1 percentage points The intervention group had a higher proportion of patients with adherence levels 480%
Average self-reported adherence: 43.2% (control) versus 57.8% (intervention); [SD ¼ 27.1, t(122) ¼ 3.06, p ¼ 0.003] The proportions with average adherence over 80% or above for the control group was 7 of 66 (10.6%) and for the intervention group 15 of 58 (25.9%) Mean ICS adherence rate greater in IVR group relative to control by a margin of 64.5–49.1% (F ¼ 9.66; p ¼ 0.0032) Mean adherence rate: 70.1% (control) versus 81.5% (SMS)
Adherence summary
Adherence measures
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540 N. Tran et al. J Asthma, 2014; 51(5): 536–543
Petrie, 2011
12
Strandbygaard, 2009
18
Bender, 2010
15
0 0 0 0 0
0 0
0
0
Strandbygaard [15] 2009 (n ¼ 26) Bender [16] 2010 (n ¼ 50) Table 3. Outcomes measured other than adherence to daily asthma medication.
adherence is a potentially important outcome to assess. Knowledge of this outcome would influence whether reminder system interventions need to be implemented on an ongoing basis or if they can be implemented on a shortterm basis to ‘‘train’’ a patient’s medication use behavior. Five of the six studies reported an improved adherence rate between 12 and 22 percentage points (Figure 2) [11,13–16], while the study conducted by Vollmer et al. [10] reported a difference of only 2 percentage points. The smaller difference in adherence rate reported by Vollmer et al. [10] could be due to the fact that subjects were passively recruited. Because the subjects in the five other studies were actively recruited, it is possible that those subjects were ready and primed to increase their adherence before the interventions began. Another explanation for why the difference in magnitude was smaller is that only 54% of the IVR calls directly communicated with the subject or left a detailed message. When the analysis was limited to subjects that had been contacted directly or left a detailed message at least two times, Vollmer et al. [10] reported a stronger intervention effect on adherence with an absolute difference of 6 percentage points. Although all of the studies in our analysis reported an improvement in adherence with the use of a reminder system, this change did not coincide with an improvement in quality of life, symptom control or pulmonary function. It is possible that the magnitude of increased medication adherence may not have been enough to surpass a threshold for improved clinical outcomes (e.g. a decrease in emergency room visits, asthma exacerbations) at the individual patient level [2]. Furthermore, the interventions may improve medication adherence, but may not be addressing all the factors that affect quality of life, control and pulmonary function (e.g. does not address exposure to triggers). It is also possible that the duration of the interventions may not have been long enough to see a significant difference in these outcomes, as the median intervention time was only 16 weeks. In addition, at the beginning of a clinical trial, subjects in the control group who know they are being monitored may adjust their behavior, thereby leading to increased adherence and improvements in clinical outcomes. It may take at least 6 months for initial improvements to revert to a more typical pattern for control participants [15].
Chatkin [11] 2006 (n ¼ 281)
Figure 2. Reported absolute percentage point improvement in adherence due to reminder systems. Studies above the dotted line reported baseline data on adherence to daily asthma medication. For these studies, percentage point differences in adherence post-intervention are adjusted for baseline levels of adherence. For studies below the dotted line, differences in adherence rates are not adjusted for baseline levels of adherence.
‘‘"’’ indicates upward shift in positive medication beliefs; ‘‘"/0’’ indicates shift in some beliefs in a direction consistent with greater adherence; ‘‘0’’ indicates no change.
20
"
15
"/0
10
Beliefs Brief Illness Perception Questionnaire (BIPQ) Beliefs in Medication Questionnaire (BMQ) Symptom control Asthma Control Test (ACT) Asthma Control Questionnaire (ACQ) Asthma Therapy Assessment Questionnaire (ATAQ) Quality of life Mini Asthma Quality of Life Questionnaire (MiniAQLQ) Asthma Quality of Life Questionnaire (AQLQ) Pulmonary function tests Peak Expiratory Flow (PEF) Exhaled Nitric Oxide (eNO) FEV1% of predicted FEV1/FVC Log Response Dose Ratio (LogRDR) to inhaled methacholine Healthcare utilization Urgent care, emergency department care or hospitalization for asthma Short-acting beta agonist use
5
0
22
0
Petrie [13] 2011 (n ¼ 147)
Chatkin, 2006
Charles [14] 2007 (n ¼ 110)
18
Outcomes measured
Charles, 2007
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541
0 0
Suggested Improvement in Adherence Rate Due to Reminder System
2
0
Vollmer [10] 2011 (n ¼ 8517)
Vollmer, 2011
0
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The lack of documented improvement in clinical outcomes should not discount the potential benefits of these interventions at the public health level [25]. An increase in medication adherence, though small in magnitude, may be enough to merit a reminder system intervention when considering the chronic disease self-management of a large population as a whole. Furthermore, Woolf et al. [26] found that far greater increases in efficacy must be achieved for the benefits of improved drug therapy to surpass the gains from improved delivery; thus, reminder systems that target patient adherence may be a better strategy for improving clinical asthma outcomes. Our analysis indicates that all of the studies evaluating reminder systems suggest an increase in medication adherence. We have identified methodological issues with current studies, as well as potential gaps in our knowledge of reminder systems for asthma medication adherence. Future studies should assess the effects of a reminder system on asthma medication adherence over the long-term. In addition, it would be important to assess the effects of such interventions on healthcare utilization and quality of life in greater depth. Finally, given the differences in uptake and acceptance of new technologies, further studies should focus on how these interventions affect asthma medication adherence in specific sub-groups of patients, such as adolescents.
Declaration of interest The authors report no conflicts of interest.
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Year
2011
2010
2009
2006
2007
2011
Author
Petrie [13]
Bender [16]
Strandbygaard [15]
Chatkin [11]
Charles [14]
Vollmer [10]
Northwest and Hawaii regions
Wellington, New Zealand
Brazil
Copenhagen NV, Denmark
Denver, Colorado
University of Auckland, New Zealand
Location
Appendix 1. Study characteristics
A diagnosis of asthma based on a clinical history and daily symptoms; age between 18 and 45 years; and a positive methacholine challenge test 12 years of age or older with moderate to severe persistent asthma. Required to have a residential telephone number (not only a mobile phone), to be able to comprehend study procedures, and to sign the appropriate informed consent agreement Requirement to take regular ICS at fixed dose, no exacerbation in the previous month or run-in period, not pregnant or lactating and using contraception if of child-bearing potential 18 years of age or older, treatment for asthma during the 12-month period prior to randomization, one or more dispensing of a respiratory medication at outpatient pharmacy during the 12month period prior to randomization, continuous KP membership
16–45 years
18–45 years
Participants recruited from flyers dispensed with asthma preventer medication and e-mails sent to members of a targeted marketing website (www.smilecity.co.nz) Study dates not described Participants recruited through newspaper advertising and at community allergy practices to National Jewish Health, a tertiary care center Study dates not described Participants recruited from advertisements in local newspapers Study dates not described
At 18 weeks, 46 of 74 (62%) control subjects and 57 of 73 (78%) intervention subjects completed the study At 9 months: 52 of 74 (70%) control subjects; 41 of 73 (56%) intervention subjects 25 of 25 (100%) control subjects and 25 of 25 (100%) intervention subjects completed the study Overall completion rate: 50 out of 50 (100%) 12 of 14 (85%) control subjects and 10 of 12 (83%) SMS subjects completed the study Overall completion rate: 22 of 26 (84%) Overall completion rate: 271 out of 281 (96.4%)
13–65 years
Participants were recruited from research volunteer databases, newspaper advertisements and informal contacts Study dates not described Participants were recruited from Kaiser Permanente Northwest (KPNW) and Hawaii (KPH) regions
46 of 55 (83%) control subjects and 44 of 55 (80%) AVRF subjects completed the study Overall completion rate was 90 of 110 (81%) 4015 of 4322 (93%) usual care subjects and 3903 of 4195 (93%) intervention subjects completed the study Overall completion rate was 7918 of 8517 (93%)
18–98 years
12 years+
Participants selected by their physicians in their own clinical setting as having asthma based on clinical and spirometric evidence November 2003 to April 2004
18–65 years
Between 16 and 45 years of age, diagnosed with asthma, but not currently adhering to their preventer medication as prescribed, and owned a mobile phone capable of receiving text messages Physician-diagnosed asthma and prescribed daily inhaled corticosteroid treatment
Age
Setting and dates
Completion rate
Inclusion criteria
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Individuals were excluded from the final analysis if they never received or qualified for an intervention call
Chronic obstructive pulmonary disease, history of any other clinically significant disease, and use of a long-acting beta agonist
Mild persistent asthma, pregnancy or breast-feeding, intention to move during the study, regular use or recent past abuse of alcohol or illicit drugs, clinically significant active medical conditions
Medical co-morbidities and a smoking history of 410 pack years
Any significant disease or disorder that might affect the results; or current participation in any other asthma-related research or clinical trial
Non-English speakers or diagnosis of chronic obstructive pulmonary disease
Exclusion criteria
DOI: 10.3109/02770903.2014.888572
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