Title page - University of East Anglia
Abstract Background: Understanding the magnitude of non-adherence in pre-marketing clinical trials and clinical practice is essential. However, accurately measuring non-adherence to medication is problematic and the variety of adherence measures and/or calculation methods has led to highly variable results.Purpose: To compare commonly used methods for measuring adherence to eye drop therapy in order to assess which methods achieve the most complete data sets over an eight month monitoring period; to quantify the magnitude of variance in adherence estimations; and to review the different methods used to calculate or interpret adherence data.Methods: Adherence was measured electronically for eight months by participants administering eye drops using a Travalert? dosing aid. The mean number of Travelert dosing aid recorded doses administered over the monitoring period was used to calculate a percentage adherence score. In addition, the value of graphically presenting Travalert dosing aid data to classify patterns of adherence behaviour was explored. The validated Morisky Measure of Adherence Scale and questions requesting participants to report the frequency of missed doses, were two measures of self-reported adherence calculated for each participant. Finally, medication possession ratio was calculated from expected repeat prescription orders compared with actual repeat prescription orders. Results: For the 208 recruited participants, self-reported adherence was the most reliable method of collecting complete data sets over the eight month period; 16% of self-reported adherence data were missing compared with 45% of Travalert dosing aid data missing at 8 months. The mean adherence measured over the monitoring period by the Travalert dosing aid was 77%. When adherence measures were dichotomised into adherent and non-adherent groups the Travalert dosing aid found 54% of participants were adherent, compared to 60% Morisky Measure of Adherence Scale and 57% frequency of missed dose self-report measures. However, there was poor agreement between the Travalert dosing aid measured adherence and self-report measures. Medication possession ratio was not a reliable measure of persistence with medication. Graphical Travalert dosing aid data presentation provided additional information about participant behaviour by indicating that most non-adherence was due to participants taking drug holidays rather than missing occasional doses.Conclusions: The analysis provided evidence about the inconsistencies between different monitoring strategies and adherence measures. Furthermore, the analysis highlighted the difficulties in collecting complete data for studies investigating chronic, slowly progressive conditions that require long-term follow-up. Future adherence studies could use multiple methods for quantifying and classifying adherence in parallel, both to maximise precision of adherence estimates and facilitate comparison between studies. However, the authors are cautious of the effect of using multiple adherence measures on participant behaviour and their potential reactivity effects is an area for future research.IntroductionFor marketing authorisation, clinical trials must be carried out to ascertain the safety, quality and efficacy of any medicine. Poor adherence to any treatment protocol can result in an underestimation of therapeutic efficacy and under-reporting of potential side effects. Such uncertainties and diminished observed treatment effects can result in failure to ascertain the optimal dosage for maximum efficacy, reduced statistical study power, the requirement for larger sample sizes and, in turn, increased study costs. ADDIN EN.CITE <EndNote><Cite><Author>Burke</Author><Year>1997</Year><RecNum>2249</RecNum><DisplayText><style face="superscript">1</style></DisplayText><record><rec-number>2249</rec-number><foreign-keys><key app="EN" db-id="xxs0xespbdasduevdr2xw0sq90z9v0trzwr5">2249</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Burke, L. E.</author><author>Dunbar-Jacob, J. M.</author><author>Hill, M. N.</author></authors></contributors><auth-address>University of Pittsburgh, School of Medicine, Department of Psychiatry, PA 15213, USA.</auth-address><titles><title>Compliance with cardiovascular disease prevention strategies: a review of the research</title><secondary-title>Ann Behav Med</secondary-title><alt-title>Annals of behavioral medicine : a publication of the Society of Behavioral Medicine</alt-title></titles><periodical><full-title>Ann Behav Med</full-title><abbr-1>Annals of behavioral medicine : a publication of the Society of Behavioral Medicine</abbr-1></periodical><alt-periodical><full-title>Ann Behav Med</full-title><abbr-1>Annals of behavioral medicine : a publication of the Society of Behavioral Medicine</abbr-1></alt-periodical><pages>239-63</pages><volume>19</volume><number>3</number><keywords><keyword>Behavior Therapy</keyword><keyword>Cardiovascular Agents/administration & dosage</keyword><keyword>Cardiovascular Diseases/*prevention & control/psychology</keyword><keyword>Diet, Fat-Restricted/psychology</keyword><keyword>Exercise/psychology</keyword><keyword>Humans</keyword><keyword>Patient Compliance/*psychology</keyword><keyword>Risk Factors</keyword><keyword>Smoking Cessation/psychology</keyword><keyword>Treatment Outcome</keyword></keywords><dates><year>1997</year><pub-dates><date>Summer</date></pub-dates></dates><isbn>0883-6612 (Print)
0883-6612 (Linking)</isbn><accession-num>9603699</accession-num><urls><related-urls><url> Furthermore, in routine clinical practice non-adherence can have a significant adverse effect on the apparent success of medication to control chronic conditions.Thus, understanding the magnitude of non-adherence in pre-marketing clinical trials and clinical practice is essential. However, accurately measuring non-adherence to medication is problematic. The literature reports a variety of adherence measures and calculation methods that have led to considerable variation in results. Currently, there is no consensus as to how non-adherence is reported or defined and gold-standard methodology for measuring adherence does not exist.PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5XYXRlcm1hbjwvQXV0aG9yPjxZZWFyPjIwMTM8L1llYXI+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ADDIN EN.CITE PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5XYXRlcm1hbjwvQXV0aG9yPjxZZWFyPjIwMTM8L1llYXI+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ADDIN EN.CITE.DATA 2, 3Patient self-report using questionnaires, interviews or diaries, all tend to overestimate adherencePEVuZE5vdGU+PENpdGU+PEF1dGhvcj5LYXNzPC9BdXRob3I+PFllYXI+MTk4NjwvWWVhcj48UmVj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ADDIN EN.CITE PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5LYXNzPC9BdXRob3I+PFllYXI+MTk4NjwvWWVhcj48UmVj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ADDIN EN.CITE.DATA 4, 5 and clinician reports also fail to detect non-adherence accurately.PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5LYXNzPC9BdXRob3I+PFllYXI+MTk4NjwvWWVhcj48UmVj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ADDIN EN.CITE PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5LYXNzPC9BdXRob3I+PFllYXI+MTk4NjwvWWVhcj48UmVj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ADDIN EN.CITE.DATA 6-8 Alternative measures of adherence have therefore been designed including: weighing bottle contents or tablet counting to establish use of medication, electronic monitoring devices such as the Medication Event Monitoring Systems (MEMS?), measuring clinical endpoints (such as blood pressure), or analysis of blood samples for drug metabolites. However, these observational methods often alert patients to the fact that their behaviour is being monitored which can cause a ‘reactivity bias’ resulting in increased adherence to medication.PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5HcmF5PC9BdXRob3I+PFllYXI+MjAwOTwvWWVhcj48UmVj
TnVtPjEwNzk8L1JlY051bT48RGlzcGxheVRleHQ+PHN0eWxlIGZhY2U9InN1cGVyc2NyaXB0Ij45
LCAxMDwvc3R5bGU+PC9EaXNwbGF5VGV4dD48cmVjb3JkPjxyZWMtbnVtYmVyPjEwNzk8L3JlYy1u
dW1iZXI+PGZvcmVpZ24ta2V5cz48a2V5IGFwcD0iRU4iIGRiLWlkPSJ4eHMweGVzcGJkYXNkdWV2
ZHIyeHcwc3E5MHo5djB0cnp3cjUiPjEwNzk8L2tleT48L2ZvcmVpZ24ta2V5cz48cmVmLXR5cGUg
bmFtZT0iSm91cm5hbCBBcnRpY2xlIj4xNzwvcmVmLXR5cGU+PGNvbnRyaWJ1dG9ycz48YXV0aG9y
cz48YXV0aG9yPkdyYXksIFQuIEEuPC9hdXRob3I+PGF1dGhvcj5PcnRvbiwgTC4gQy48L2F1dGhv
cj48YXV0aG9yPkhlbnNvbiwgRC48L2F1dGhvcj48YXV0aG9yPkhhcnBlciwgUi48L2F1dGhvcj48
YXV0aG9yPldhdGVybWFuLCBILjwvYXV0aG9yPjwvYXV0aG9ycz48L2NvbnRyaWJ1dG9ycz48YXV0
aC1hZGRyZXNzPkFjYWRlbWljIERlcGFydG1lbnQgb2YgT3BodGhhbG1vbG9neSwgTWFuY2hlc3Rl
ciBSb3lhbCBFeWUgSG9zcGl0YWwsIE94Zm9yZCBSb2FkLCBNYW5jaGVzdGVyLCBVSywgTTEzIDlX
SC4gdHJpc2guZ3JheUBtYW5jaGVzdGVyLmFjLnVrPC9hdXRoLWFkZHJlc3M+PHRpdGxlcz48dGl0
bGU+SW50ZXJ2ZW50aW9ucyBmb3IgaW1wcm92aW5nIGFkaGVyZW5jZSB0byBvY3VsYXIgaHlwb3Rl
bnNpdmUgdGhlcmFweTwvdGl0bGU+PHNlY29uZGFyeS10aXRsZT5Db2NocmFuZSBEYXRhYmFzZSBT
eXN0IFJldjwvc2Vjb25kYXJ5LXRpdGxlPjwvdGl0bGVzPjxwZXJpb2RpY2FsPjxmdWxsLXRpdGxl
PkNvY2hyYW5lIERhdGFiYXNlIFN5c3QgUmV2PC9mdWxsLXRpdGxlPjxhYmJyLTE+VGhlIENvY2hy
YW5lIGRhdGFiYXNlIG9mIHN5c3RlbWF0aWMgcmV2aWV3czwvYWJici0xPjwvcGVyaW9kaWNhbD48
cGFnZXM+Q0QwMDYxMzI8L3BhZ2VzPjxudW1iZXI+MjwvbnVtYmVyPjxlZGl0aW9uPjIwMDkvMDQv
MTc8L2VkaXRpb24+PGtleXdvcmRzPjxrZXl3b3JkPkdsYXVjb21hL2RydWcgdGhlcmFweTwva2V5
d29yZD48a2V5d29yZD5IdW1hbnM8L2tleXdvcmQ+PGtleXdvcmQ+Kk1lZGljYXRpb24gQWRoZXJl
bmNlPC9rZXl3b3JkPjxrZXl3b3JkPk9jdWxhciBIeXBlcnRlbnNpb24vKmRydWcgdGhlcmFweTwv
a2V5d29yZD48a2V5d29yZD5PcGh0aGFsbWljIFNvbHV0aW9ucy9hZG1pbmlzdHJhdGlvbiAmYW1w
OyBkb3NhZ2U8L2tleXdvcmQ+PGtleXdvcmQ+UmFuZG9taXplZCBDb250cm9sbGVkIFRyaWFscyBh
cyBUb3BpYzwva2V5d29yZD48L2tleXdvcmRzPjxkYXRlcz48eWVhcj4yMDA5PC95ZWFyPjwvZGF0
ZXM+PGlzYm4+MTQ2OS00OTNYIChFbGVjdHJvbmljKSYjeEQ7MTM2MS02MTM3IChMaW5raW5nKTwv
aXNibj48YWNjZXNzaW9uLW51bT4xOTM3MDYyNzwvYWNjZXNzaW9uLW51bT48dXJscz48cmVsYXRl
ZC11cmxzPjx1cmw+aHR0cDovL3d3dy5uY2JpLm5sbS5uaWguZ292L2VudHJlei9xdWVyeS5mY2dp
P2NtZD1SZXRyaWV2ZSZhbXA7ZGI9UHViTWVkJmFtcDtkb3B0PUNpdGF0aW9uJmFtcDtsaXN0X3Vp
ZHM9MTkzNzA2Mjc8L3VybD48L3JlbGF0ZWQtdXJscz48L3VybHM+PGVsZWN0cm9uaWMtcmVzb3Vy
Y2UtbnVtPjEwLjEwMDIvMTQ2NTE4NTguQ0QwMDYxMzIucHViMjwvZWxlY3Ryb25pYy1yZXNvdXJj
ZS1udW0+PGxhbmd1YWdlPmVuZzwvbGFuZ3VhZ2U+PC9yZWNvcmQ+PC9DaXRlPjxDaXRlPjxBdXRo
b3I+TGl0Y2hlci1LZWxseTwvQXV0aG9yPjxZZWFyPjIwMDc8L1llYXI+PFJlY051bT4yMjUwPC9S
ZWNOdW0+PHJlY29yZD48cmVjLW51bWJlcj4yMjUwPC9yZWMtbnVtYmVyPjxmb3JlaWduLWtleXM+
PGtleSBhcHA9IkVOIiBkYi1pZD0ieHhzMHhlc3BiZGFzZHVldmRyMnh3MHNxOTB6OXYwdHJ6d3I1
Ij4yMjUwPC9rZXk+PC9mb3JlaWduLWtleXM+PHJlZi10eXBlIG5hbWU9IkpvdXJuYWwgQXJ0aWNs
ZSI+MTc8L3JlZi10eXBlPjxjb250cmlidXRvcnM+PGF1dGhvcnM+PGF1dGhvcj5MaXRjaGVyLUtl
bGx5LCBMLjwvYXV0aG9yPjxhdXRob3I+S2VsbGVybWFuLCBRLjwvYXV0aG9yPjxhdXRob3I+SGFu
YXVlciwgUy4gQi48L2F1dGhvcj48YXV0aG9yPlN0b25lLCBBLiBBLjwvYXV0aG9yPjwvYXV0aG9y
cz48L2NvbnRyaWJ1dG9ycz48YXV0aC1hZGRyZXNzPkFwcGxpZWQgQmVoYXZpb3JhbCBNZWRpY2lu
ZSBSZXNlYXJjaCBJbnN0aXR1dGUsIERlcGFydG1lbnQgb2YgUHN5Y2hpYXRyeSBhbmQgQmVoYXZp
b3JhbCBTY2llbmNlLCBTdG9ueSBCcm9vayBVbml2ZXJzaXR5LCBOWSAxMTc5NC04NzkwLCBVU0Eu
IExlaWdoYW5uLkxpdGNoZXJAc3VueXNiLmVkdTwvYXV0aC1hZGRyZXNzPjx0aXRsZXM+PHRpdGxl
PkZlYXNpYmlsaXR5IGFuZCB1dGlsaXR5IG9mIGFuIGVsZWN0cm9uaWMgZGlhcnkgdG8gYXNzZXNz
IHNlbGYtcmVwb3J0IHN5bXB0b21zIGluIHBhdGllbnRzIHdpdGggaW5mbGFtbWF0b3J5IGJvd2Vs
IGRpc2Vhc2U8L3RpdGxlPjxzZWNvbmRhcnktdGl0bGU+QW5uIEJlaGF2IE1lZDwvc2Vjb25kYXJ5
LXRpdGxlPjxhbHQtdGl0bGU+QW5uYWxzIG9mIGJlaGF2aW9yYWwgbWVkaWNpbmUgOiBhIHB1Ymxp
Y2F0aW9uIG9mIHRoZSBTb2NpZXR5IG9mIEJlaGF2aW9yYWwgTWVkaWNpbmU8L2FsdC10aXRsZT48
L3RpdGxlcz48cGVyaW9kaWNhbD48ZnVsbC10aXRsZT5Bbm4gQmVoYXYgTWVkPC9mdWxsLXRpdGxl
PjxhYmJyLTE+QW5uYWxzIG9mIGJlaGF2aW9yYWwgbWVkaWNpbmUgOiBhIHB1YmxpY2F0aW9uIG9m
IHRoZSBTb2NpZXR5IG9mIEJlaGF2aW9yYWwgTWVkaWNpbmU8L2FiYnItMT48L3BlcmlvZGljYWw+
PGFsdC1wZXJpb2RpY2FsPjxmdWxsLXRpdGxlPkFubiBCZWhhdiBNZWQ8L2Z1bGwtdGl0bGU+PGFi
YnItMT5Bbm5hbHMgb2YgYmVoYXZpb3JhbCBtZWRpY2luZSA6IGEgcHVibGljYXRpb24gb2YgdGhl
IFNvY2lldHkgb2YgQmVoYXZpb3JhbCBNZWRpY2luZTwvYWJici0xPjwvYWx0LXBlcmlvZGljYWw+
PHBhZ2VzPjIwNy0xMjwvcGFnZXM+PHZvbHVtZT4zMzwvdm9sdW1lPjxudW1iZXI+MjwvbnVtYmVy
PjxrZXl3b3Jkcz48a2V5d29yZD5BZHVsdDwva2V5d29yZD48a2V5d29yZD5BZ2VkPC9rZXl3b3Jk
PjxrZXl3b3JkPkNvbGl0aXMsIFVsY2VyYXRpdmUvKmRpYWdub3Npcy9wc3ljaG9sb2d5PC9rZXl3
b3JkPjxrZXl3b3JkPipDb21wdXRlcnMsIEhhbmRoZWxkPC9rZXl3b3JkPjxrZXl3b3JkPkNyb2hu
IERpc2Vhc2UvKmRpYWdub3Npcy9wc3ljaG9sb2d5PC9rZXl3b3JkPjxrZXl3b3JkPkZlYXNpYmls
aXR5IFN0dWRpZXM8L2tleXdvcmQ+PGtleXdvcmQ+RmVtYWxlPC9rZXl3b3JkPjxrZXl3b3JkPkh1
bWFuczwva2V5d29yZD48a2V5d29yZD5NYWxlPC9rZXl3b3JkPjxrZXl3b3JkPipNZWRpY2FsIFJl
Y29yZHM8L2tleXdvcmQ+PGtleXdvcmQ+TWlkZGxlIEFnZWQ8L2tleXdvcmQ+PGtleXdvcmQ+UGF0
aWVudCBDb21wbGlhbmNlL3BzeWNob2xvZ3k8L2tleXdvcmQ+PGtleXdvcmQ+UGlsb3QgUHJvamVj
dHM8L2tleXdvcmQ+PGtleXdvcmQ+U29mdHdhcmU8L2tleXdvcmQ+PC9rZXl3b3Jkcz48ZGF0ZXM+
PHllYXI+MjAwNzwveWVhcj48cHViLWRhdGVzPjxkYXRlPkFwcjwvZGF0ZT48L3B1Yi1kYXRlcz48
L2RhdGVzPjxpc2JuPjE1MzItNDc5NiAoRWxlY3Ryb25pYykmI3hEOzA4ODMtNjYxMiAoTGlua2lu
Zyk8L2lzYm4+PGFjY2Vzc2lvbi1udW0+MTc0NDc4NzM8L2FjY2Vzc2lvbi1udW0+PHVybHM+PHJl
bGF0ZWQtdXJscz48dXJsPmh0dHA6Ly93d3cubmNiaS5ubG0ubmloLmdvdi9wdWJtZWQvMTc0NDc4
NzM8L3VybD48L3JlbGF0ZWQtdXJscz48L3VybHM+PGVsZWN0cm9uaWMtcmVzb3VyY2UtbnVtPjEw
LjEwODAvMDg4MzY2MTA3MDEzMTAwNzg8L2VsZWN0cm9uaWMtcmVzb3VyY2UtbnVtPjwvcmVjb3Jk
PjwvQ2l0ZT48L0VuZE5vdGU+AAAA
ADDIN EN.CITE PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5HcmF5PC9BdXRob3I+PFllYXI+MjAwOTwvWWVhcj48UmVj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ADDIN EN.CITE.DATA 9, 10 Studies using electronic monitoring devices have provided evidence that such reactivity bias can cause an initial improvement in adherence, but that this usually decreases after approximately two months of routine use of the adherence measure.PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5EaWF6PC9BdXRob3I+PFllYXI+MjAwMTwvWWVhcj48UmVj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ADDIN EN.CITE PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5EaWF6PC9BdXRob3I+PFllYXI+MjAwMTwvWWVhcj48UmVj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ADDIN EN.CITE.DATA 11, 12 A further proposed advantage of electronic monitoring devices is that they can be used to compare individual and collective ‘behaviour patterns’, thus potentially providing a more refined measure of complex adherence behaviours to enable identification of clinically significant non-adherent patient behaviour.PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5SaWNoYXJkc29uPC9BdXRob3I+PFllYXI+MjAxMzwvWWVh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ADDIN EN.CITE PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5SaWNoYXJkc29uPC9BdXRob3I+PFllYXI+MjAxMzwvWWVh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ADDIN EN.CITE.DATA 12-15 Short persistence accounts can take many different forms, and can jeopardize treatment effectiveness which leads to treatment discontinuation. ADDIN EN.CITE <EndNote><Cite><Author>Blaschke</Author><Year>2012</Year><RecNum>2317</RecNum><DisplayText><style face="superscript">16</style></DisplayText><record><rec-number>2317</rec-number><foreign-keys><key app="EN" db-id="xxs0xespbdasduevdr2xw0sq90z9v0trzwr5">2317</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Blaschke, T. F.</author><author>Osterberg, L.</author><author>Vrijens, B.</author><author>Urquhart, J.</author></authors></contributors><auth-address>Department of Medicine, Stanford University School of Medicine, Stanford, California 94305, USA. blaschke@stanford.edu</auth-address><titles><title>Adherence to medications: insights arising from studies on the unreliable link between prescribed and actual drug dosing histories</title><secondary-title>Annu Rev Pharmacol Toxicol</secondary-title><alt-title>Annual review of pharmacology and toxicology</alt-title></titles><periodical><full-title>Annu Rev Pharmacol Toxicol</full-title><abbr-1>Annual review of pharmacology and toxicology</abbr-1></periodical><alt-periodical><full-title>Annu Rev Pharmacol Toxicol</full-title><abbr-1>Annual review of pharmacology and toxicology</abbr-1></alt-periodical><pages>275-301</pages><volume>52</volume><keywords><keyword>*Dose-Response Relationship, Drug</keyword><keyword>Drug Administration Schedule</keyword><keyword>Drug Design</keyword><keyword>Humans</keyword><keyword>*Patient Compliance</keyword><keyword>Pharmaceutical Preparations/*administration & dosage</keyword><keyword>Pharmacokinetics</keyword></keywords><dates><year>2012</year></dates><isbn>1545-4304 (Electronic)
0362-1642 (Linking)</isbn><accession-num>21942628</accession-num><urls><related-urls><url> For example if therapeutic benefit is reliant upon medication administration at a particular time of day, timing accuracy will better reflect clinical outcome than measuring the number of doses taken if they are at the wrong time of day. An 80% adherence rate is widely recognised as ‘acceptable’ for many systemic medications ADDIN EN.CITE <EndNote><Cite><Author>J.</Author><Year>1979</Year><RecNum>1052</RecNum><DisplayText><style face="superscript">17</style></DisplayText><record><rec-number>1052</rec-number><foreign-keys><key app="EN" db-id="xxs0xespbdasduevdr2xw0sq90z9v0trzwr5">1052</key></foreign-keys><ref-type name="Book Section">5</ref-type><contributors><authors><author>Sackett, D. </author><author>Snow, J.</author></authors><secondary-authors><author>Haynes, B.</author><author>Wayne Taylor, D. </author><author>Sacket, D. </author></secondary-authors></contributors><titles><title>Magnitude and Measurement of Compliance </title><secondary-title>Compliance in Healthcare</secondary-title></titles><dates><year>1979</year></dates><pub-location>Baltimore and London</pub-location><publisher>The John Hopkins University Press</publisher><urls></urls></record></Cite></EndNote>17 but to be clinically relevant, an 'acceptable' adherence level should be determined by its impact on clinical outcome.PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5PbHRob2ZmPC9BdXRob3I+PFllYXI+MjAwNTwvWWVhcj48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ADDIN EN.CITE PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5PbHRob2ZmPC9BdXRob3I+PFllYXI+MjAwNTwvWWVhcj48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ADDIN EN.CITE.DATA 18 Persistence with medication use, as determined by repeat prescription or dispensing counts, is considered to provide more objective non-adherence data compared with self-report, since it remains relatively unaffected by patient desirability to appear adherent, or by memory bias.PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5DYXRlPC9BdXRob3I+PFllYXI+MjAxMzwvWWVhcj48UmVj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ADDIN EN.CITE PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5DYXRlPC9BdXRob3I+PFllYXI+MjAxMzwvWWVhcj48UmVj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ADDIN EN.CITE.DATA 14, 15 Furthermore, the ‘remote’ method of persistence data collection may be less likely to elicit behaviour change than electronic monitoring. Persistence data can be collected from all participants regardless of their participation status since data can still be collected from participants who leave a study if prior consent has been given for this. However, in the UK, there is no central claims database so prescribing data must be requested from individual General Practices where patients are registered; this can limit the amount of information retrieved since each Practice must first agree to provide the requested information, for which there is normally an administration charge. Furthermore, it must also be considered that persistence is only a proxy measure of daily adherence and does not account for patients who collect but do not take their medication.PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5Tb3JlbnNlbjwvQXV0aG9yPjxZZWFyPjIwMDU8L1llYXI+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ADDIN EN.CITE PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5Tb3JlbnNlbjwvQXV0aG9yPjxZZWFyPjIwMDU8L1llYXI+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ADDIN EN.CITE.DATA 19 Glaucoma is a chronic disease, often asymptomatic in the early stages but later leading to progressive visual field loss and eventual blindness if left untreated.PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5MZXNrZTwvQXV0aG9yPjxZZWFyPjIwMDM8L1llYXI+PFJl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ADDIN EN.CITE PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5MZXNrZTwvQXV0aG9yPjxZZWFyPjIwMDM8L1llYXI+PFJl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ADDIN EN.CITE.DATA 20 Regular use of eye drops to control the intraocular pressure can prevent the onset or reduce the rate of progression of manifest glaucoma. ADDIN EN.CITE <EndNote><Cite><Author>Heijl</Author><Year>2002</Year><RecNum>2238</RecNum><DisplayText><style face="superscript">21</style></DisplayText><record><rec-number>2238</rec-number><foreign-keys><key app="EN" db-id="xxs0xespbdasduevdr2xw0sq90z9v0trzwr5">2238</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Heijl, A.</author><author>Leske, M. C.</author><author>Bengtsson, B.</author><author>Hyman, L.</author><author>Hussein, M.</author></authors></contributors><auth-address>Department of Ophthalmology, Malmo University Hospital, SE-20502 Malmo, Sweden. anders.heijl@oftal.mas.lu.se</auth-address><titles><title>Reduction of intraocular pressure and glaucoma progression: results from the Early Manifest Glaucoma Trial</title><secondary-title>Archives of ophthalmology</secondary-title></titles><periodical><full-title>Archives of ophthalmology</full-title><abbr-1>Arch Ophthalmol</abbr-1></periodical><pages>1268-79</pages><volume>120</volume><number>10</number><edition>2002/10/09</edition><keywords><keyword>Adrenergic beta-Antagonists/therapeutic use</keyword><keyword>Aged</keyword><keyword>Aged, 80 and over</keyword><keyword>Betaxolol/therapeutic use</keyword><keyword>Disease Progression</keyword><keyword>Female</keyword><keyword>Glaucoma, Open-Angle/*physiopathology/*therapy</keyword><keyword>Humans</keyword><keyword>*Intraocular Pressure/drug effects</keyword><keyword>Laser Therapy</keyword><keyword>Male</keyword><keyword>Middle Aged</keyword><keyword>Single-Blind Method</keyword><keyword>Trabeculectomy</keyword><keyword>Treatment Outcome</keyword></keywords><dates><year>2002</year><pub-dates><date>Oct</date></pub-dates></dates><isbn>0003-9950 (Print)
0003-9950 (Linking)</isbn><accession-num>12365904</accession-num><urls><related-urls><url> [pii]</electronic-resource-num><language>eng</language></record></Cite></EndNote>21 Although the present study was limited to patients using glaucoma medications, the relevance of these analyses may be applicable to adherence measurement for other medicines used in the management of chronic disease.The purpose of the present analysis was to compare commonly used methods for measuring adherence to glaucoma medication using data collected from the Norwich Adherence Glaucoma Study. ADDIN EN.CITE <EndNote><Cite><Author>Cate</Author><Year>2012</Year><RecNum>2146</RecNum><DisplayText><style face="superscript">22</style></DisplayText><record><rec-number>2146</rec-number><foreign-keys><key app="EN" db-id="xxs0xespbdasduevdr2xw0sq90z9v0trzwr5">2146</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Cate, H.</author><author>Bhattacharya, D.</author><author>Clark, A.</author><author>Fordham, R.</author><author>Notley, C.</author><author>Broadway, D. C.</author></authors></contributors><titles><title>Protocol for a randomised controlled trial to estimate the effects and costs of a patient centred educational intervention in glaucoma management</title><secondary-title>BMC Ophthalmol</secondary-title></titles><periodical><full-title>BMC Ophthalmol</full-title></periodical><pages>57</pages><volume>12</volume><number>1</number><edition>2012/11/23</edition><dates><year>2012</year><pub-dates><date>Nov 22</date></pub-dates></dates><isbn>1471-2415 (Electronic)
1471-2415 (Linking)</isbn><accession-num>23171166</accession-num><urls></urls><electronic-resource-num>10.1186/1471-2415-12-57</electronic-resource-num><remote-database-provider>NLM</remote-database-provider><language>Eng</language></record></Cite></EndNote>22 The objectives were to assess which methods achieved the greatest complete datasets over an eight month monitoring period; compare the results from different data collection methods; and review the different methods used to calculate or interpret non-adherence data.MethodsData were drawn from the Norwich Adherence Glaucoma Study which was a randomized controlled trial conducted in the Glaucoma Clinic of a UK National Health Service (NHS) teaching hospital to compare effects of an educational and supportive intervention on adherence behaviour over that achieved with standard care. ADDIN EN.CITE <EndNote><Cite><Author>Cate</Author><Year>2012</Year><RecNum>2146</RecNum><DisplayText><style face="superscript">22</style></DisplayText><record><rec-number>2146</rec-number><foreign-keys><key app="EN" db-id="xxs0xespbdasduevdr2xw0sq90z9v0trzwr5">2146</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Cate, H.</author><author>Bhattacharya, D.</author><author>Clark, A.</author><author>Fordham, R.</author><author>Notley, C.</author><author>Broadway, D. C.</author></authors></contributors><titles><title>Protocol for a randomised controlled trial to estimate the effects and costs of a patient centred educational intervention in glaucoma management</title><secondary-title>BMC Ophthalmol</secondary-title></titles><periodical><full-title>BMC Ophthalmol</full-title></periodical><pages>57</pages><volume>12</volume><number>1</number><edition>2012/11/23</edition><dates><year>2012</year><pub-dates><date>Nov 22</date></pub-dates></dates><isbn>1471-2415 (Electronic)
1471-2415 (Linking)</isbn><accession-num>23171166</accession-num><urls></urls><electronic-resource-num>10.1186/1471-2415-12-57</electronic-resource-num><remote-database-provider>NLM</remote-database-provider><language>Eng</language></record></Cite></EndNote>22 The study was conducted in accordance with the protocol that received ethical approval from the Norfolk Research Ethics Committee, UK and for which participants gave their written consent. The methods for collecting adherence data and social demographic data have been described previously. ADDIN EN.CITE <EndNote><Cite><Author>Cate</Author><Year>2012</Year><RecNum>2146</RecNum><DisplayText><style face="superscript">22</style></DisplayText><record><rec-number>2146</rec-number><foreign-keys><key app="EN" db-id="xxs0xespbdasduevdr2xw0sq90z9v0trzwr5">2146</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Cate, H.</author><author>Bhattacharya, D.</author><author>Clark, A.</author><author>Fordham, R.</author><author>Notley, C.</author><author>Broadway, D. C.</author></authors></contributors><titles><title>Protocol for a randomised controlled trial to estimate the effects and costs of a patient centred educational intervention in glaucoma management</title><secondary-title>BMC Ophthalmol</secondary-title></titles><periodical><full-title>BMC Ophthalmol</full-title></periodical><pages>57</pages><volume>12</volume><number>1</number><edition>2012/11/23</edition><dates><year>2012</year><pub-dates><date>Nov 22</date></pub-dates></dates><isbn>1471-2415 (Electronic)
1471-2415 (Linking)</isbn><accession-num>23171166</accession-num><urls></urls><electronic-resource-num>10.1186/1471-2415-12-57</electronic-resource-num><remote-database-provider>NLM</remote-database-provider><language>Eng</language></record></Cite></EndNote>22 Adherence measures Travalert Dosing Aid?: Participants were given a Travalert? dosing aid (TDA, Alcon Laboratories, Inc., Forth Worth, TX, USA) with which to administer their travoprost eye drops once daily in the evening, for the duration of the eight month study. The mean number of doses administered over the monitoring period, recorded by the TDA, was used to calculate a percentage adherence score using an adjusted adherence calculator PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5DYXRlPC9BdXRob3I+PFllYXI+MjAxMTwvWWVhcj48UmVj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==
ADDIN EN.CITE PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5DYXRlPC9BdXRob3I+PFllYXI+MjAxMTwvWWVhcj48UmVj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==
ADDIN EN.CITE.DATA 22, 23 as presented in Figure 1. If patients stopped using the travoprost as part of their clinical care, the reason for this was recorded. The TDA data were also used to produce each individual’s dosing history using a chronology plot to display the days (24-hours) between each dosing event. The resulting graphical representation of adherence can be used to visualise and classify patterns of adherence behaviour as described previously by Ajit et al. ADDIN EN.CITE <EndNote><Cite><Author>Ajit</Author><Year>2010</Year><RecNum>1930</RecNum><DisplayText><style face="superscript">14</style></DisplayText><record><rec-number>1930</rec-number><foreign-keys><key app="EN" db-id="xxs0xespbdasduevdr2xw0sq90z9v0trzwr5">1930</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Ajit, R. R.</author><author>Fenerty, C. H.</author><author>Henson, D. B.</author></authors></contributors><auth-address>Manchester Royal Eye Hospital, Manchester, UK.</auth-address><titles><title>Patterns and rate of adherence to glaucoma therapy using an electronic dosing aid</title><secondary-title>Eye (Lond)</secondary-title></titles><periodical><full-title>Eye (Lond)</full-title></periodical><pages>1338-43</pages><volume>24</volume><number>8</number><edition>2010/03/27</edition><keywords><keyword>Adult</keyword><keyword>Aged</keyword><keyword>Aged, 80 and over</keyword><keyword>Antihypertensive Agents/*administration & dosage</keyword><keyword>Cloprostenol/administration & dosage/*analogs & derivatives</keyword><keyword>Cohort Studies</keyword><keyword>Drug Monitoring/*instrumentation</keyword><keyword>Female</keyword><keyword>Glaucoma/*drug therapy</keyword><keyword>Humans</keyword><keyword>Male</keyword><keyword>Medication Adherence/*statistics & numerical data</keyword><keyword>Middle Aged</keyword><keyword>Ophthalmic Solutions/administration & dosage</keyword><keyword>Prospective Studies</keyword></keywords><dates><year>2010</year><pub-dates><date>Aug</date></pub-dates></dates><isbn>1476-5454 (Electronic)
0950-222X (Linking)</isbn><accession-num>20339390</accession-num><urls><related-urls><url> [pii]
10.1038/eye.2010.27</electronic-resource-num><language>eng</language></record></Cite></EndNote>14 ,Cate et al. ADDIN EN.CITE <EndNote><Cite><Author>Cate</Author><Year>2013</Year><RecNum>2182</RecNum><DisplayText><style face="superscript">15</style></DisplayText><record><rec-number>2182</rec-number><foreign-keys><key app="EN" db-id="xxs0xespbdasduevdr2xw0sq90z9v0trzwr5">2182</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Cate, H.</author><author>Bhattacharya, D.</author><author>Clark, A.</author><author>Holland, R.</author><author>Broadway, D. C.</author></authors></contributors><auth-address>1] Eye Department, Norfolk and Norwich University Hospital, NHS Foundation Trust, Norwich, UK [2] School of Pharmacy, University of East Anglia, Norwich, UK.</auth-address><titles><title>Patterns of adherence behaviour for patients with glaucoma</title><secondary-title>Eye</secondary-title><alt-title>Eye (Lond)</alt-title></titles><alt-periodical><full-title>Eye (Lond)</full-title></alt-periodical><edition>2013/01/19</edition><dates><year>2013</year><pub-dates><date>Jan 18</date></pub-dates></dates><isbn>1476-5454 (Electronic)
0950-222X (Linking)</isbn><accession-num>23328800</accession-num><urls><related-urls><url> and Blaschke et al. ADDIN EN.CITE <EndNote><Cite><Author>Blaschke</Author><Year>2012</Year><RecNum>2317</RecNum><DisplayText><style face="superscript">16</style></DisplayText><record><rec-number>2317</rec-number><foreign-keys><key app="EN" db-id="xxs0xespbdasduevdr2xw0sq90z9v0trzwr5">2317</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Blaschke, T. F.</author><author>Osterberg, L.</author><author>Vrijens, B.</author><author>Urquhart, J.</author></authors></contributors><auth-address>Department of Medicine, Stanford University School of Medicine, Stanford, California 94305, USA. blaschke@stanford.edu</auth-address><titles><title>Adherence to medications: insights arising from studies on the unreliable link between prescribed and actual drug dosing histories</title><secondary-title>Annu Rev Pharmacol Toxicol</secondary-title><alt-title>Annual review of pharmacology and toxicology</alt-title></titles><periodical><full-title>Annu Rev Pharmacol Toxicol</full-title><abbr-1>Annual review of pharmacology and toxicology</abbr-1></periodical><alt-periodical><full-title>Annu Rev Pharmacol Toxicol</full-title><abbr-1>Annual review of pharmacology and toxicology</abbr-1></alt-periodical><pages>275-301</pages><volume>52</volume><keywords><keyword>*Dose-Response Relationship, Drug</keyword><keyword>Drug Administration Schedule</keyword><keyword>Drug Design</keyword><keyword>Humans</keyword><keyword>*Patient Compliance</keyword><keyword>Pharmaceutical Preparations/*administration & dosage</keyword><keyword>Pharmacokinetics</keyword></keywords><dates><year>2012</year></dates><isbn>1545-4304 (Electronic)
0362-1642 (Linking)</isbn><accession-num>21942628</accession-num><urls><related-urls><url> A perfectly adherent participant would have dosing event recorded at 1 day intervals. However, participants who had missed one dose would have had a 2 day interval between doses and so forth, thus showing the number of days that elapsed between dosing events. Therefore, whilst the aggregate percentage of dosing events during the total monitoring period may be the same, the dosing history data reveal different patterns of behaviour. Seven categories were used to classify adherence; (1) Discontinued after a short time due to (1a) side effects or (1b) no response to treatment, (2) adherence greater than 80% and subdivided into (2a) greater than 97% and type (2b) less than 96%, (3) had less than 80% adherence over the course of the study due to ‘drug holidays’ (participants who had a break in eye drop use for 7 or more days) and were subdivided into type (3a) ‘Drug holidays’ mixed with a variable dosing pattern and type (3b) drug holidays only, and (4) partients who had less than 80% adherence with variable and frequent missed doses. Self-reported adherence: A participant self-administered questionnaire was completed at two months and then at eight months after randomisation and intervention to capture self-reported adherence data. Two self-report adherence measures were utilised: the Frequency of Missed Dose (FMD) which is a one-question parameter developed for the present study, inviting participants to report the number of eye drop doses missed each month (twice a week or more, once a week, once a month, or never) and the Morisky Measure of Adherence Scale ADDIN EN.CITE <EndNote><Cite><Author>Morisky</Author><Year>1986</Year><RecNum>567</RecNum><DisplayText><style face="superscript">24</style></DisplayText><record><rec-number>567</rec-number><foreign-keys><key app="EN" db-id="xxs0xespbdasduevdr2xw0sq90z9v0trzwr5">567</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Morisky, D. E.</author><author>Green, L. W.</author><author>Levine, D. M.</author></authors></contributors><titles><title>Concurrent and predictive validity of a self-reported measure of medication adherence</title><secondary-title>Med Care</secondary-title></titles><periodical><full-title>Medical care</full-title><abbr-1>Med Care</abbr-1></periodical><pages>67-74</pages><volume>24</volume><number>1</number><edition>1986/01/01</edition><keywords><keyword>Humans</keyword><keyword>Hypertension/*drug therapy</keyword><keyword>Medical History Taking</keyword><keyword>Outpatient Clinics, Hospital</keyword><keyword>*Patient Compliance</keyword><keyword>Patient Education as Topic</keyword><keyword>Physician-Patient Relations</keyword><keyword>Probability</keyword><keyword>Psychometrics</keyword></keywords><dates><year>1986</year><pub-dates><date>Jan</date></pub-dates></dates><isbn>0025-7079 (Print)
0025-7079 (Linking)</isbn><accession-num>3945130</accession-num><urls><related-urls><url> (MMAS) which is a four-item validated measure. For the FMD, participants reporting having missed their medication more than once a month were considered non-adherent.Self-reported adherence using the MMAS score was calculated for each participant. Participants that answered ‘yes’ to a question scored 1: thus scores ranged from 0-3. Participants who scored 0 were considered to be “adherent”, participants scoring 1-3 were considered “non-adherent” a classification used in a previous glaucoma adherence study. ADDIN EN.CITE <EndNote><Cite><Author>Cate</Author><Year>2013</Year><RecNum>2182</RecNum><DisplayText><style face="superscript">15</style></DisplayText><record><rec-number>2182</rec-number><foreign-keys><key app="EN" db-id="xxs0xespbdasduevdr2xw0sq90z9v0trzwr5">2182</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Cate, H.</author><author>Bhattacharya, D.</author><author>Clark, A.</author><author>Holland, R.</author><author>Broadway, D. C.</author></authors></contributors><auth-address>1] Eye Department, Norfolk and Norwich University Hospital, NHS Foundation Trust, Norwich, UK [2] School of Pharmacy, University of East Anglia, Norwich, UK.</auth-address><titles><title>Patterns of adherence behaviour for patients with glaucoma</title><secondary-title>Eye</secondary-title><alt-title>Eye (Lond)</alt-title></titles><alt-periodical><full-title>Eye (Lond)</full-title></alt-periodical><edition>2013/01/19</edition><dates><year>2013</year><pub-dates><date>Jan 18</date></pub-dates></dates><isbn>1476-5454 (Electronic)
0950-222X (Linking)</isbn><accession-num>23328800</accession-num><urls><related-urls><url> Medication Possession Ratio (MPR): In the UK, patients repeat prescription history is maintained by their General Practitioner. In order to retrieve this information, with participant consent, the researcher wrote to each individual participant’s General Practitioner to ask for their repeat prescribing records including, drug name, date of issue, and prescribed days of treatment. Payment was made for this administrative task via an existing Research Payment Contract held by the Primary Care Research Network and participating General Practitioners. From these data a measure of expected repeat prescription orders and actual repeat prescription orders were used to calculate two MPR values: MPRa HYPERLINK \l "_ENREF_25" \o "Friedman, 2007 #591" PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5GcmllZG1hbjwvQXV0aG9yPjxZZWFyPjIwMDc8L1llYXI+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ADDIN EN.CITE PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5GcmllZG1hbjwvQXV0aG9yPjxZZWFyPjIwMDc8L1llYXI+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ADDIN EN.CITE.DATA 25 which used the average travoprost drop count ADDIN EN.CITE <EndNote><Cite><Author>Fiscella</Author><Year>2003</Year><RecNum>1905</RecNum><DisplayText><style face="superscript">26</style></DisplayText><record><rec-number>1905</rec-number><foreign-keys><key app="EN" db-id="xxs0xespbdasduevdr2xw0sq90z9v0trzwr5">1905</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Fiscella, R. G.</author><author>Green, A.</author><author>Patuszynski, D. H.</author><author>Wilensky, J.</author></authors></contributors><auth-address>Department of Pharmacy Practice, University of Illinois at Chicago, Illinois 60612, USA. Fisc@UIC.EDU</auth-address><titles><title>Medical therapy cost considerations for glaucoma</title><secondary-title>Am J Ophthalmol</secondary-title></titles><periodical><full-title>Am J Ophthalmol</full-title></periodical><pages>18-25</pages><volume>136</volume><number>1</number><edition>2003/07/02</edition><keywords><keyword>Adrenergic alpha-Agonists/economics</keyword><keyword>Adrenergic beta-Antagonists/economics</keyword><keyword>Antihypertensive Agents/*economics</keyword><keyword>Carbonic Anhydrase Inhibitors/economics</keyword><keyword>Costs and Cost Analysis</keyword><keyword>*Drug Costs</keyword><keyword>Drug Prescriptions/economics</keyword><keyword>Drugs, Generic/economics</keyword><keyword>Glaucoma/drug therapy/*economics</keyword><keyword>Humans</keyword><keyword>Ophthalmic Solutions/*economics</keyword><keyword>Prospective Studies</keyword><keyword>Prostaglandins/economics</keyword><keyword>United States</keyword></keywords><dates><year>2003</year><pub-dates><date>Jul</date></pub-dates></dates><isbn>0002-9394 (Print)
0002-9394 (Linking)</isbn><accession-num>12834665</accession-num><urls><related-urls><url> [pii]</electronic-resource-num><language>eng</language></record></Cite></EndNote>26; and MPRb which used the UK general prescribing instruction to renew eye drop prescriptions every 28 days (Figure 1).Statistical analysisDescriptive statistics were used to characterise the demographics of the study population. Adherence measured by the TDA was calculated for the mean of the total monitoring period and the mean of months one and two. Additionally, a binary classification of adherence score was used (‘adherent’ if the score was 80% and ‘non-adherent’ if the score was <80%) for the same time periods (total period, months one and two). A repeated measures analysis-of-variance was carried out (with time measured in months) to assess for any difference in adherence over time. A Cohen’s Kappa test was used to compare (i) agreement between TDA data at month two and eight for participants with missing data in order to determine if non-adherence scores may have been effected by missing data; the assumption being made that participants with missing data might have been more likely to have poor adherence, being less motivated to complete questionnaires, or return their TDAs to the research team, (ii) agreement between self-report data at month two and eight for participants with missing TDA data, and (iii) agreement between self-report measures (MMAS and FMD) and TDA dichotomised scores of adherence at two months and eight months to determine if non-adherence was the same between measures and at the different time points that adherence was measured. The mean and median MPRa and MPRb scores were calculated and compared to TDA adherence scores using a Spearman’s rank co-efficient test to compare measures. A binary classification of persistence score was used (‘adherent’ if the score was 1.0 or above and ‘non-adherent’ if the score was below 1.0) for the total period of the study. ResultsA total of 208 participants were recruited of which 50.5% were male and the mean age was 70.4 (SD 11.1) years. Further demographic data about the Norwich Adherence Glaucoma Study cohort has been published previously. ADDIN EN.CITE <EndNote><Cite><Author>Cate</Author><Year>2014</Year><RecNum>2271</RecNum><DisplayText><style face="superscript">27</style></DisplayText><record><rec-number>2271</rec-number><foreign-keys><key app="EN" db-id="xxs0xespbdasduevdr2xw0sq90z9v0trzwr5">2271</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Cate, H.</author><author>Bhattacharya, D.</author><author>Clark, A.</author><author>Fordham, R.</author><author>Holland, R.</author><author>Broadway, D. C.</author></authors></contributors><auth-address>Norfolk & Norwich University Hospital NHS Trust, Glaucoma Research Unit, Level 2, West Block, Colney Lane, Norwich NR4 7UY, UK. heidi.cate@nnuh.nhs.uk.</auth-address><titles><title>Improving adherence to glaucoma medication: a randomised controlled trial of a patient-centred intervention (The Norwich Adherence Glaucoma Study)</title><secondary-title>BMC Ophthalmol</secondary-title><alt-title>BMC ophthalmology</alt-title></titles><periodical><full-title>BMC Ophthalmol</full-title></periodical><pages>32</pages><volume>14</volume><dates><year>2014</year></dates><isbn>1471-2415 (Electronic)
1471-2415 (Linking)</isbn><accession-num>24655814</accession-num><urls><related-urls><url> Missing data The reasons for incomplete adherence data are summarised in Table 1. Questionnaire data provided the most complete datasets over the eight month period relative to health centre and TDA data which were comparable in terms of completeness at the eight month data collection point. The reason for the failure of the TDA was not always possible to establish. In some cases the internal mechanics of the device appeared to have been tampered with by the participant but it was not possible to determine in which cases the device had failed due to deliberate tampering or genuine device malfunction. MPR data were missing where health centres refused to provide the prescribing data when requested. Adherence measuresThe mean adherence rate measured by the TDA was 73.7% (standard deviation, 26.4) for the first two months of monitoring; and 76.6% (standard deviation 20.7) for the total eight month period. A repeated measures analysis-of-variance of TDA percentage adherence for each month found no significant differences between months. The number of individuals with <80% adherence for the first two months and therefore considered to be non-adherent was 78 (46.7%) compared with 52 (45.6%) for the eight month period. Assuming that participants with missing data could more likely be non-adherent, further analysis of missing data found that of the 78 participants that were non-adherent at month two, only 25 (32%) had missing data at any time point during the period of monitoring and there was no statistically significant association between participants with non-adherence and missing data during the study (Kappa 0.006, p=0.935). Mean adherence at month two for those with missing data at month eight was 73% (standard deviation, 26) compared with 74% (standard deviation, 26) for those with complete data at month eight. Table 2 presents the adherence status for each of the three measures of adherence and their agreement between two and eight months. Little change was observed between patients reporting being adherent at month two but later at month eight reporting that they were non-adherent as demonstrated by the moderate agreement ADDIN EN.CITE <EndNote><Cite><Author>Landis</Author><Year>1977</Year><RecNum>2295</RecNum><DisplayText><style face="superscript">28</style></DisplayText><record><rec-number>2295</rec-number><foreign-keys><key app="EN" db-id="xxs0xespbdasduevdr2xw0sq90z9v0trzwr5">2295</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Landis, J. R.</author><author>Koch, G. G.</author></authors></contributors><titles><title>The measurement of observer agreement for categorical data</title><secondary-title>Biometrics</secondary-title><alt-title>Biometrics</alt-title></titles><periodical><full-title>Biometrics</full-title><abbr-1>Biometrics</abbr-1></periodical><alt-periodical><full-title>Biometrics</full-title><abbr-1>Biometrics</abbr-1></alt-periodical><pages>159-74</pages><volume>33</volume><number>1</number><keywords><keyword>Humans</keyword><keyword>Multiple Sclerosis/*diagnosis</keyword><keyword>*Statistics as Topic</keyword></keywords><dates><year>1977</year><pub-dates><date>Mar</date></pub-dates></dates><isbn>0006-341X (Print)
0006-341X (Linking)</isbn><accession-num>843571</accession-num><urls><related-urls><url> for MMAS and FMD. The change was even less with the TDA dichotomised score analysis as indicated by the substantial agreement. ADDIN EN.CITE <EndNote><Cite><Author>Landis</Author><Year>1977</Year><RecNum>2295</RecNum><DisplayText><style face="superscript">28</style></DisplayText><record><rec-number>2295</rec-number><foreign-keys><key app="EN" db-id="xxs0xespbdasduevdr2xw0sq90z9v0trzwr5">2295</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Landis, J. R.</author><author>Koch, G. G.</author></authors></contributors><titles><title>The measurement of observer agreement for categorical data</title><secondary-title>Biometrics</secondary-title><alt-title>Biometrics</alt-title></titles><periodical><full-title>Biometrics</full-title><abbr-1>Biometrics</abbr-1></periodical><alt-periodical><full-title>Biometrics</full-title><abbr-1>Biometrics</abbr-1></alt-periodical><pages>159-74</pages><volume>33</volume><number>1</number><keywords><keyword>Humans</keyword><keyword>Multiple Sclerosis/*diagnosis</keyword><keyword>*Statistics as Topic</keyword></keywords><dates><year>1977</year><pub-dates><date>Mar</date></pub-dates></dates><isbn>0006-341X (Print)
0006-341X (Linking)</isbn><accession-num>843571</accession-num><urls><related-urls><url> determine if missing data had an effect on participants self-reporting, a further analysis was carried out which found that 15% of participants with missing TDA data reported to be non-adherent at month eight compared to 25% with full TDA data (similar results for both were found using both FMD and MMAS measures). Tables 3 and 4 present agreement between FMD, MMAS and TDA measured adherence; Table 3 at month two and Table 4 at month eight. Adherence using the two self-report measures, MMAS and FMD, had substantial agreement ADDIN EN.CITE <EndNote><Cite><Author>Landis</Author><Year>1977</Year><RecNum>2295</RecNum><DisplayText><style face="superscript">28</style></DisplayText><record><rec-number>2295</rec-number><foreign-keys><key app="EN" db-id="xxs0xespbdasduevdr2xw0sq90z9v0trzwr5">2295</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Landis, J. R.</author><author>Koch, G. G.</author></authors></contributors><titles><title>The measurement of observer agreement for categorical data</title><secondary-title>Biometrics</secondary-title><alt-title>Biometrics</alt-title></titles><periodical><full-title>Biometrics</full-title><abbr-1>Biometrics</abbr-1></periodical><alt-periodical><full-title>Biometrics</full-title><abbr-1>Biometrics</abbr-1></alt-periodical><pages>159-74</pages><volume>33</volume><number>1</number><keywords><keyword>Humans</keyword><keyword>Multiple Sclerosis/*diagnosis</keyword><keyword>*Statistics as Topic</keyword></keywords><dates><year>1977</year><pub-dates><date>Mar</date></pub-dates></dates><isbn>0006-341X (Print)
0006-341X (Linking)</isbn><accession-num>843571</accession-num><urls><related-urls><url> at months two and eight however they were only in slight agreement with the TDA dichotomised scores at months two and eight. TDA and MMAS were not statistically significant at month two. Figures 2 and 3 show the distribution of FMD and MMAS categorical data compared with TDA measured adherence for the total study period.Figure 4 presents adherence behaviour patterns derived from the TDA data. Most participants’ had good adherence (>80% but <97%; 2b). Non-adherent behaviour was primarily due to participants taking drug holidays rather than just missing occasional doses.The mean possession ratio was 1.89 (standard deviation 0.66) using the MPRa calculation (refill on expiration of bottle) and 0.94 (standard deviation 0.34) using MPRb (expected refill bottle every 28 days). There was a strong positive correlation between MPRa and MPRb calculations (Spearman’s co-efficient 0.901, p<0.0001) and therefore further analysis was carried out using MPRb data. The majority of participants (71%) had the correct prescription count to remain persistent with medication over the course of the eight month study period as indicated in Figure 5 by the column assigned an MPR of 1 or higher. There was only a weak positive correlation between MPRb and adherence calculated by the TDA (Spearman’s co-efficient 0.216, p=0.041) displayed in Figure 6. However, transcription of the raw data for analysis highlighted differences in the way eye drops were prescribed and dispensed which created inaccuracies in the data. Prescribing practices resulted in the following anomalies: As recommended, regardless of whether patients were prescribed unilateral or bilateral dosing, all patients received the same size bottle of eye drops. Thus, patients prescribed unilateral dosing had double the amount of medication required compared to those prescribed bilateral dosing. Patients did not consistently receive one bottle of drops per month. When multiple bottles were given it was not possible to establish the reason but common explanations from participants were: that the pharmacist dispensed two bottles of eye drops for bilateral dosing, one to be used for each eye (thus, patients had double the amount of medication required with a more complex dosing regimen requiring the opening and use of separate bottles for each eye); multiple refills were given on request if patients found they were running out of drops; patients reported stockpiling before going on vacation or because it was difficult to visit the pharmacy to collect refills; or patients reported losing drops or forgetting them if they had been staying away from home and had ordered replacements.The dichotomised scores of adherence persistence were not statistically significant when compared with FMD, MMAS and TDA dichotomised adherence scores. Since the quality of data was questionable because of prescribing practices, which led to participants possessing more medication then required, the dichotomised MPR scores were not compared further.Discussion Discordance between the different methods of measurement compared in the present study and differing challenges associated with each method of data collection prohibits determination of a definitive measure of adherence. Self-report questionnaires provided the most complete datasets for the eight month period of study. Conversely, almost a quarter of the MPR data were missing due to health centres not providing prescribing data for research purposes despite being offered payment for this administrative task. Only one similar UK study using prospective collection of prescribing data has been identified from the literaturePEVuZE5vdGU+PENpdGU+PEF1dGhvcj5HcmF5PC9BdXRob3I+PFllYXI+MjAxMjwvWWVhcj48UmVj
TnVtPjIxNDA8L1JlY051bT48RGlzcGxheVRleHQ+PHN0eWxlIGZhY2U9InN1cGVyc2NyaXB0Ij4y
OTwvc3R5bGU+PC9EaXNwbGF5VGV4dD48cmVjb3JkPjxyZWMtbnVtYmVyPjIxNDA8L3JlYy1udW1i
ZXI+PGZvcmVpZ24ta2V5cz48a2V5IGFwcD0iRU4iIGRiLWlkPSJ4eHMweGVzcGJkYXNkdWV2ZHIy
eHcwc3E5MHo5djB0cnp3cjUiPjIxNDA8L2tleT48L2ZvcmVpZ24ta2V5cz48cmVmLXR5cGUgbmFt
ZT0iSm91cm5hbCBBcnRpY2xlIj4xNzwvcmVmLXR5cGU+PGNvbnRyaWJ1dG9ycz48YXV0aG9ycz48
YXV0aG9yPkdyYXksIFQuIEEuPC9hdXRob3I+PGF1dGhvcj5GZW5lcnR5LCBDLjwvYXV0aG9yPjxh
dXRob3I+SGFycGVyLCBSLjwvYXV0aG9yPjxhdXRob3I+U3BlbmNlciwgQS4gRi48L2F1dGhvcj48
YXV0aG9yPkNhbXBiZWxsLCBNLjwvYXV0aG9yPjxhdXRob3I+SGVuc29uLCBELiBCLjwvYXV0aG9y
PjxhdXRob3I+V2F0ZXJtYW4sIEguPC9hdXRob3I+PC9hdXRob3JzPjwvY29udHJpYnV0b3JzPjxh
dXRoLWFkZHJlc3M+U2Nob29sIG9mIEJpb21lZGljaW5lLCBVbml2ZXJzaXR5IG9mIE1hbmNoZXN0
ZXIsIE1hbmNoZXN0ZXIsIFVLLiB0cmlzaC5ncmF5QG1hbmNoZXN0ZXIuYWMudWs8L2F1dGgtYWRk
cmVzcz48dGl0bGVzPjx0aXRsZT5JbmRpdmlkdWFsaXNlZCBwYXRpZW50IGNhcmUgYXMgYW4gYWRq
dW5jdCB0byBzdGFuZGFyZCBjYXJlIGZvciBwcm9tb3RpbmcgYWRoZXJlbmNlIHRvIG9jdWxhciBo
eXBvdGVuc2l2ZSB0aGVyYXB5OiBhbiBleHBsb3JhdG9yeSByYW5kb21pc2VkIGNvbnRyb2xsZWQg
dHJpYWw8L3RpdGxlPjxzZWNvbmRhcnktdGl0bGU+RXllIChMb25kKTwvc2Vjb25kYXJ5LXRpdGxl
PjxhbHQtdGl0bGU+RXllIChMb25kKTwvYWx0LXRpdGxlPjwvdGl0bGVzPjxwZXJpb2RpY2FsPjxm
dWxsLXRpdGxlPkV5ZSAoTG9uZCk8L2Z1bGwtdGl0bGU+PC9wZXJpb2RpY2FsPjxhbHQtcGVyaW9k
aWNhbD48ZnVsbC10aXRsZT5FeWUgKExvbmQpPC9mdWxsLXRpdGxlPjwvYWx0LXBlcmlvZGljYWw+
PHBhZ2VzPjQwNy0xNzwvcGFnZXM+PHZvbHVtZT4yNjwvdm9sdW1lPjxudW1iZXI+MzwvbnVtYmVy
PjxlZGl0aW9uPjIwMTEvMTEvMTk8L2VkaXRpb24+PGtleXdvcmRzPjxrZXl3b3JkPkFkdWx0PC9r
ZXl3b3JkPjxrZXl3b3JkPkFnZWQ8L2tleXdvcmQ+PGtleXdvcmQ+QWdlZCwgODAgYW5kIG92ZXI8
L2tleXdvcmQ+PGtleXdvcmQ+RmVtYWxlPC9rZXl3b3JkPjxrZXl3b3JkPkZvbGxvdy1VcCBTdHVk
aWVzPC9rZXl3b3JkPjxrZXl3b3JkPipIZWFsdGggS25vd2xlZGdlLCBBdHRpdHVkZXMsIFByYWN0
aWNlPC9rZXl3b3JkPjxrZXl3b3JkPkh1bWFuczwva2V5d29yZD48a2V5d29yZD5JbmRpdmlkdWFs
aXplZCBNZWRpY2luZTwva2V5d29yZD48a2V5d29yZD5JbnRyYW9jdWxhciBQcmVzc3VyZS9waHlz
aW9sb2d5PC9rZXl3b3JkPjxrZXl3b3JkPk1hbGU8L2tleXdvcmQ+PGtleXdvcmQ+TWVkaWNhdGlv
biBBZGhlcmVuY2UvKnBzeWNob2xvZ3kvc3RhdGlzdGljcyAmYW1wOyBudW1lcmljYWwgZGF0YTwv
a2V5d29yZD48a2V5d29yZD5NaWRkbGUgQWdlZDwva2V5d29yZD48a2V5d29yZD5PY3VsYXIgSHlw
b3RlbnNpb24vKmRydWcgdGhlcmFweS9waHlzaW9wYXRob2xvZ3kvKnBzeWNob2xvZ3k8L2tleXdv
cmQ+PGtleXdvcmQ+KlBhdGllbnQgQ2FyZSBQbGFubmluZzwva2V5d29yZD48a2V5d29yZD5RdWFs
aXR5IG9mIEhlYWx0aCBDYXJlL3N0YW5kYXJkczwva2V5d29yZD48L2tleXdvcmRzPjxkYXRlcz48
eWVhcj4yMDEyPC95ZWFyPjxwdWItZGF0ZXM+PGRhdGU+TWFyPC9kYXRlPjwvcHViLWRhdGVzPjwv
ZGF0ZXM+PGlzYm4+MTQ3Ni01NDU0IChFbGVjdHJvbmljKSYjeEQ7MDk1MC0yMjJYIChMaW5raW5n
KTwvaXNibj48YWNjZXNzaW9uLW51bT4yMjA5NDMwMzwvYWNjZXNzaW9uLW51bT48d29yay10eXBl
PlJhbmRvbWl6ZWQgQ29udHJvbGxlZCBUcmlhbCYjeEQ7UmVzZWFyY2ggU3VwcG9ydCwgTm9uLVUu
Uy4gR292JmFwb3M7dDwvd29yay10eXBlPjx1cmxzPjxyZWxhdGVkLXVybHM+PHVybD5odHRwOi8v
d3d3Lm5jYmkubmxtLm5paC5nb3YvcHVibWVkLzIyMDk0MzAzPC91cmw+PC9yZWxhdGVkLXVybHM+
PC91cmxzPjxjdXN0b20yPjMyOTkwMTI8L2N1c3RvbTI+PGVsZWN0cm9uaWMtcmVzb3VyY2UtbnVt
PjEwLjEwMzgvZXllLjIwMTEuMjY5PC9lbGVjdHJvbmljLXJlc291cmNlLW51bT48bGFuZ3VhZ2U+
ZW5nPC9sYW5ndWFnZT48L3JlY29yZD48L0NpdGU+PC9FbmROb3RlPn==
ADDIN EN.CITE PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5HcmF5PC9BdXRob3I+PFllYXI+MjAxMjwvWWVhcj48UmVj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ADDIN EN.CITE.DATA 29 but in this study the authors did not report any limitations in data collection. Other UK studies using prescribing data have used retrospective data collection methodsPEVuZE5vdGU+PENpdGU+PEF1dGhvcj5NY0Nvd2FuPC9BdXRob3I+PFllYXI+MjAxMzwvWWVhcj48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ADDIN EN.CITE PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5NY0Nvd2FuPC9BdXRob3I+PFllYXI+MjAxMzwvWWVhcj48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ADDIN EN.CITE.DATA 30-33 of which missing or inaccurate data was often noted as a possible limitation, although the magnitude of the problem was not quantified.Previous studies have reported that the TDA accurately recorded drop administration, but the longest of these studies was only for a three month period.PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5Pa2VrZTwvQXV0aG9yPjxZZWFyPjIwMDk8L1llYXI+PFJl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ADDIN EN.CITE PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5Pa2VrZTwvQXV0aG9yPjxZZWFyPjIwMDk8L1llYXI+PFJl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ADDIN EN.CITE.DATA 14, 34, 35 The present study found that the TDA was relatively successful at measuring adherence for the initial two month period. However, by eight months of follow-up, data attrition was high. Retrieval of data from the TDA due to device failure, which was outside of the control of either patient or researcher, accounted for the greatest loss of daily electronic data for the eight month period. In addition, when treatment was changed, it rendered the TDA useless since the TDA aperture only holds Travatan shaped bottles. Therefore, calculating the average adherence score using TDA over the total monitoring period was the least successful of the three studied methods. The TDA data, however, did provide the additional benefit of being able to graphically present participant patterns of drop usage.PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5Baml0PC9BdXRob3I+PFllYXI+MjAxMDwvWWVhcj48UmVj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ADDIN EN.CITE PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5Baml0PC9BdXRob3I+PFllYXI+MjAxMDwvWWVhcj48UmVj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ADDIN EN.CITE.DATA 14, 15 Comparing patterns of drop usage determined that ‘drug holidays’ were the predominate type of non-adherent behaviour. In contrast to incidental missed doses, patterns of drug holidays may be indicative of a more intentional non-adherent behaviour trait when a patient chooses not to use their medication for longer periods of time.PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5MYWNleTwvQXV0aG9yPjxZZWFyPjIwMDk8L1llYXI+PFJl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ADDIN EN.CITE PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5MYWNleTwvQXV0aG9yPjxZZWFyPjIwMDk8L1llYXI+PFJl
Y051bT41NDk8L1JlY051bT48RGlzcGxheVRleHQ+PHN0eWxlIGZhY2U9InN1cGVyc2NyaXB0Ij4z
NiwgMzc8L3N0eWxlPjwvRGlzcGxheVRleHQ+PHJlY29yZD48cmVjLW51bWJlcj41NDk8L3JlYy1u
dW1iZXI+PGZvcmVpZ24ta2V5cz48a2V5IGFwcD0iRU4iIGRiLWlkPSJ4eHMweGVzcGJkYXNkdWV2
ZHIyeHcwc3E5MHo5djB0cnp3cjUiPjU0OTwva2V5PjwvZm9yZWlnbi1rZXlzPjxyZWYtdHlwZSBu
YW1lPSJKb3VybmFsIEFydGljbGUiPjE3PC9yZWYtdHlwZT48Y29udHJpYnV0b3JzPjxhdXRob3Jz
PjxhdXRob3I+TGFjZXksIEouPC9hdXRob3I+PGF1dGhvcj5DYXRlLCBILjwvYXV0aG9yPjxhdXRo
b3I+QnJvYWR3YXksIEQuIEMuPC9hdXRob3I+PC9hdXRob3JzPjwvY29udHJpYnV0b3JzPjxhdXRo
LWFkZHJlc3M+RGVwYXJ0bWVudCBvZiBPcGh0aGFsbW9sb2d5LCBHbGF1Y29tYSBSZXNlYXJjaCBV
bml0LCBOb3Jmb2xrIGFuZCBOb3J3aWNoIFVuaXZlcnNpdHkgSG9zcGl0YWwgTkhTIFRydXN0LCBO
b3J3aWNoLCBVSy48L2F1dGgtYWRkcmVzcz48dGl0bGVzPjx0aXRsZT5CYXJyaWVycyB0byBhZGhl
cmVuY2Ugd2l0aCBnbGF1Y29tYSBtZWRpY2F0aW9uczogYSBxdWFsaXRhdGl2ZSByZXNlYXJjaCBz
dHVkeTwvdGl0bGU+PHNlY29uZGFyeS10aXRsZT5FeWUgKExvbmQpPC9zZWNvbmRhcnktdGl0bGU+
PC90aXRsZXM+PHBlcmlvZGljYWw+PGZ1bGwtdGl0bGU+RXllIChMb25kKTwvZnVsbC10aXRsZT48
L3BlcmlvZGljYWw+PHBhZ2VzPjkyNC0zMjwvcGFnZXM+PHZvbHVtZT4yMzwvdm9sdW1lPjxudW1i
ZXI+NDwvbnVtYmVyPjxlZGl0aW9uPjIwMDgvMDQvMjY8L2VkaXRpb24+PGRhdGVzPjx5ZWFyPjIw
MDk8L3llYXI+PHB1Yi1kYXRlcz48ZGF0ZT5BcHI8L2RhdGU+PC9wdWItZGF0ZXM+PC9kYXRlcz48
aXNibj4xNDc2LTU0NTQgKEVsZWN0cm9uaWMpJiN4RDswOTUwLTIyMlggKExpbmtpbmcpPC9pc2Ju
PjxhY2Nlc3Npb24tbnVtPjE4NDM3MTgyPC9hY2Nlc3Npb24tbnVtPjx1cmxzPjxyZWxhdGVkLXVy
bHM+PHVybD5odHRwOi8vd3d3Lm5jYmkubmxtLm5paC5nb3YvZW50cmV6L3F1ZXJ5LmZjZ2k/Y21k
PVJldHJpZXZlJmFtcDtkYj1QdWJNZWQmYW1wO2RvcHQ9Q2l0YXRpb24mYW1wO2xpc3RfdWlkcz0x
ODQzNzE4MjwvdXJsPjwvcmVsYXRlZC11cmxzPjwvdXJscz48ZWxlY3Ryb25pYy1yZXNvdXJjZS1u
dW0+ZXllMjAwODEwMyBbcGlpXSYjeEQ7MTAuMTAzOC9leWUuMjAwOC4xMDM8L2VsZWN0cm9uaWMt
cmVzb3VyY2UtbnVtPjxsYW5ndWFnZT5lbmc8L2xhbmd1YWdlPjwvcmVjb3JkPjwvQ2l0ZT48Q2l0
ZT48QXV0aG9yPkdhZGthcmk8L0F1dGhvcj48WWVhcj4yMDEyPC9ZZWFyPjxSZWNOdW0+MjE5MTwv
UmVjTnVtPjxyZWNvcmQ+PHJlYy1udW1iZXI+MjE5MTwvcmVjLW51bWJlcj48Zm9yZWlnbi1rZXlz
PjxrZXkgYXBwPSJFTiIgZGItaWQ9Inh4czB4ZXNwYmRhc2R1ZXZkcjJ4dzBzcTkwejl2MHRyendy
NSI+MjE5MTwva2V5PjwvZm9yZWlnbi1rZXlzPjxyZWYtdHlwZSBuYW1lPSJKb3VybmFsIEFydGlj
bGUiPjE3PC9yZWYtdHlwZT48Y29udHJpYnV0b3JzPjxhdXRob3JzPjxhdXRob3I+R2Fka2FyaSwg
QS4gUy48L2F1dGhvcj48YXV0aG9yPk1jSG9ybmV5LCBDLiBBLjwvYXV0aG9yPjwvYXV0aG9ycz48
L2NvbnRyaWJ1dG9ycz48YXV0aC1hZGRyZXNzPlUsUywgT3V0Y29tZXMgUmVzZWFyY2gsIE1lcmNr
ICZhbXA7IENvLCwgSW5jLCAzNTEgTm9ydGggU3VtbmV5dG93biBQaWtlLCBOb3J0aCBXYWxlcywg
UEEgMTk0NTQsIFVTQS4gYWJoaWppdF9nYWRrYXJpQG1lcmNrLmNvbTwvYXV0aC1hZGRyZXNzPjx0
aXRsZXM+PHRpdGxlPlVuaW50ZW50aW9uYWwgbm9uLWFkaGVyZW5jZSB0byBjaHJvbmljIHByZXNj
cmlwdGlvbiBtZWRpY2F0aW9uczogaG93IHVuaW50ZW50aW9uYWwgaXMgaXQgcmVhbGx5PzwvdGl0
bGU+PHNlY29uZGFyeS10aXRsZT5CTUMgaGVhbHRoIHNlcnZpY2VzIHJlc2VhcmNoPC9zZWNvbmRh
cnktdGl0bGU+PGFsdC10aXRsZT5CTUMgSGVhbHRoIFNlcnYgUmVzPC9hbHQtdGl0bGU+PC90aXRs
ZXM+PHBlcmlvZGljYWw+PGZ1bGwtdGl0bGU+Qk1DIGhlYWx0aCBzZXJ2aWNlcyByZXNlYXJjaDwv
ZnVsbC10aXRsZT48YWJici0xPkJNQyBIZWFsdGggU2VydiBSZXM8L2FiYnItMT48L3BlcmlvZGlj
YWw+PGFsdC1wZXJpb2RpY2FsPjxmdWxsLXRpdGxlPkJNQyBoZWFsdGggc2VydmljZXMgcmVzZWFy
Y2g8L2Z1bGwtdGl0bGU+PGFiYnItMT5CTUMgSGVhbHRoIFNlcnYgUmVzPC9hYmJyLTE+PC9hbHQt
cGVyaW9kaWNhbD48cGFnZXM+OTg8L3BhZ2VzPjx2b2x1bWU+MTI8L3ZvbHVtZT48ZWRpdGlvbj4y
MDEyLzA0LzE5PC9lZGl0aW9uPjxrZXl3b3Jkcz48a2V5d29yZD5BZHVsdDwva2V5d29yZD48a2V5
d29yZD5BZ2VkPC9rZXl3b3JkPjxrZXl3b3JkPkFzdGhtYS9kcnVnIHRoZXJhcHkvcHN5Y2hvbG9n
eTwva2V5d29yZD48a2V5d29yZD5DaHJvbmljIERpc2Vhc2UvKmRydWcgdGhlcmFweS9wc3ljaG9s
b2d5PC9rZXl3b3JkPjxrZXl3b3JkPkNyb3NzLVNlY3Rpb25hbCBTdHVkaWVzPC9rZXl3b3JkPjxr
ZXl3b3JkPkRlcHJlc3NpdmUgRGlzb3JkZXIvZHJ1ZyB0aGVyYXB5PC9rZXl3b3JkPjxrZXl3b3Jk
PkRpYWJldGVzIE1lbGxpdHVzL2RydWcgdGhlcmFweTwva2V5d29yZD48a2V5d29yZD5EcnVnIFBy
ZXNjcmlwdGlvbnMvKnN0YXRpc3RpY3MgJmFtcDsgbnVtZXJpY2FsIGRhdGE8L2tleXdvcmQ+PGtl
eXdvcmQ+RmVtYWxlPC9rZXl3b3JkPjxrZXl3b3JkPipIZWFsdGggS25vd2xlZGdlLCBBdHRpdHVk
ZXMsIFByYWN0aWNlPC9rZXl3b3JkPjxrZXl3b3JkPkhlYWx0aCBTdGF0dXM8L2tleXdvcmQ+PGtl
eXdvcmQ+SHVtYW5zPC9rZXl3b3JkPjxrZXl3b3JkPkh5cGVydGVuc2lvbi9kcnVnIHRoZXJhcHk8
L2tleXdvcmQ+PGtleXdvcmQ+TG9naXN0aWMgTW9kZWxzPC9rZXl3b3JkPjxrZXl3b3JkPk1hbGU8
L2tleXdvcmQ+PGtleXdvcmQ+TWlkZGxlIEFnZWQ8L2tleXdvcmQ+PGtleXdvcmQ+T3N0ZW9wb3Jv
c2lzL2RydWcgdGhlcmFweTwva2V5d29yZD48a2V5d29yZD5QYXRpZW50IENvbXBsaWFuY2UvKnBz
eWNob2xvZ3kvc3RhdGlzdGljcyAmYW1wOyBudW1lcmljYWwgZGF0YTwva2V5d29yZD48a2V5d29y
ZD5QcmVkaWN0aXZlIFZhbHVlIG9mIFRlc3RzPC9rZXl3b3JkPjxrZXl3b3JkPlByZXZhbGVuY2U8
L2tleXdvcmQ+PGtleXdvcmQ+UXVlc3Rpb25uYWlyZXM8L2tleXdvcmQ+PGtleXdvcmQ+U2lja25l
c3MgSW1wYWN0IFByb2ZpbGU8L2tleXdvcmQ+PGtleXdvcmQ+U29jaWFsIENsYXNzPC9rZXl3b3Jk
PjxrZXl3b3JkPlVuaXRlZCBTdGF0ZXM8L2tleXdvcmQ+PC9rZXl3b3Jkcz48ZGF0ZXM+PHllYXI+
MjAxMjwveWVhcj48L2RhdGVzPjxpc2JuPjE0NzItNjk2MyAoRWxlY3Ryb25pYykmI3hEOzE0NzIt
Njk2MyAoTGlua2luZyk8L2lzYm4+PGFjY2Vzc2lvbi1udW0+MjI1MTAyMzU8L2FjY2Vzc2lvbi1u
dW0+PHdvcmstdHlwZT5SZXNlYXJjaCBTdXBwb3J0LCBOb24tVS5TLiBHb3YmYXBvczt0PC93b3Jr
LXR5cGU+PHVybHM+PHJlbGF0ZWQtdXJscz48dXJsPmh0dHA6Ly93d3cubmNiaS5ubG0ubmloLmdv
di9wdWJtZWQvMjI1MTAyMzU8L3VybD48L3JlbGF0ZWQtdXJscz48L3VybHM+PGN1c3RvbTI+MzM3
NTE5ODwvY3VzdG9tMj48ZWxlY3Ryb25pYy1yZXNvdXJjZS1udW0+MTAuMTE4Ni8xNDcyLTY5NjMt
MTItOTg8L2VsZWN0cm9uaWMtcmVzb3VyY2UtbnVtPjxsYW5ndWFnZT5lbmc8L2xhbmd1YWdlPjwv
cmVjb3JkPjwvQ2l0ZT48L0VuZE5vdGU+AG==
ADDIN EN.CITE.DATA 36, 37 Thus, reviewing usage patterns rather than average adherence scores may be more useful in establishing the cause(s) of observed non-adherence. Adherence pattern observation in turn can provide invaluable information for guiding the selection of intervention(s) most appropriate for supporting patients to adhere to their prescribed therapy.Patient self-reporting remains a popular method for collection of adherence information in both clinical practice and research. However, it is of concern that a discrepancy was observed between self-reported non-adherence, which was greater at eight months than two months, and TDA measured non-adherence which did not increase at any time during the eight month follow-up even when accounting for participants with missing data. If non-adherent participants had failed to return their TDA devices, thus creating more missing TDA data, this could have been a reactivity bias. However, magnitude of adherence at two months was comparable for participants with full 8-month data and those who subsequently went on to have missing TDA data. Therefore those who had missing TDA data but still provided self-reported adherence data were not likely to have been a less adherent cohort in comparison with those who had full TDA data. If one were to accept that the level of electronic monitoring accuracy remained constant over the monitoring period, then participants were poor reporters of adherence since their reporting became less accurate over time or they were inclined to over-report adherence within the first two months of observation. The electronic monitoring used in the present study may have caused a reactivity bias not previously identified in previous studies. Adherence measured electronically did not diminish over time as previously reportedPEVuZE5vdGU+PENpdGU+PEF1dGhvcj5HcmF5PC9BdXRob3I+PFllYXI+MjAwOTwvWWVhcj48UmVj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ADDIN EN.CITE PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5HcmF5PC9BdXRob3I+PFllYXI+MjAwOTwvWWVhcj48UmVj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ADDIN EN.CITE.DATA 9, 10 and the results did not replicate previous theories of the likely short term reactivity bias time found in observational studies. Either participants in the present study were naturally very adherent, or there may have been a more long term reactivity bias caused by study participation and/or the monitoring effects of the TDA that improved adherence behaviour for the duration of follow-up. These phenomena, often referred to as mere measurement effects, are proposed to cause behavioural changes in intervention studies and are the subject of ongoing debate. ADDIN EN.CITE <EndNote><Cite><Author>Mankarious</Author><Year>2014</Year><RecNum>2294</RecNum><DisplayText><style face="superscript">38</style></DisplayText><record><rec-number>2294</rec-number><foreign-keys><key app="EN" db-id="xxs0xespbdasduevdr2xw0sq90z9v0trzwr5">2294</key></foreign-keys><ref-type name="Electronic Article">43</ref-type><contributors><authors><author>Mankarious, E.</author><author>Kothe, E.</author></authors></contributors><titles><title>A meta-analysis of the effects of measuring theory of planned behaviour constructs on behaviour within prospective studies</title><secondary-title>Health Psychology Review</secondary-title></titles><periodical><full-title>Health Psychol Rev</full-title><abbr-1>Health psychology review</abbr-1></periodical><section>07 Jul 2014</section><dates><year>2014</year><pub-dates><date>08 July 2014</date></pub-dates></dates><publisher>Routledge</publisher><urls></urls><electronic-resource-num>10.1080/17437199.2014.927722</electronic-resource-num></record></Cite></EndNote>38 The multiple measures of adherence may have had an effect on participants self-reporting of adherence. When participants are aware that multiple measures are being used, a synergistic relationship may occur which emphasises adherent behaviour and can cause a greater study reactivity bias. A future study may be able to assess if self-report of adherence changes when participants are being monitored with an electronic monitor.The calculation of MPRs with eye drops was found to be complex due to inaccuracies in the data caused by variation in prescribing conduct. In addition, unlike tablets or syrups, it is not possible to determine the volume of liquid correctly instilled in the eye as it relies upon the dexterity of the patient to instil the correct amount of liquid into the eye on the first attempt. If a patient were to miss the eye for example, they may need to apply another drop whilst with prolonged squeezing excessive liquid flows from the bottle resulting in the administration of more than one measured drop. Thus, absence of a fixed dose measure with respect to eye drops and differences in prescribing protocols can easily lead to erroneous MPR calculations. Inaccurate calculation of MPR may have been the reason why the present study failed to identify a strong correlation between TDA and MPR measures. In a previous UK study using MPR calculations, the same 28-day calculation for refills was used but the authors did not describe any of the potential inaccuracies or limitations in collecting the data as described in the present study.PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5HcmF5PC9BdXRob3I+PFllYXI+MjAxMjwvWWVhcj48UmVj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ADDIN EN.CITE PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5HcmF5PC9BdXRob3I+PFllYXI+MjAxMjwvWWVhcj48UmVj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ADDIN EN.CITE.DATA 29 The present study observations are worth further consideration since the complexity of repeat prescription administration itself, and variation in health care professional practice with respect to prescribing medication, may have a role to play in patient attitudes to medication use. The present analysis provided further evidence of the potential bias induced by using self-report and electronic tools to measure adherence and the difficulties of using routine data to calculate MPRs, particularly with respect to eye drops within the UK prescribing system. Furthermore, whilst electronic monitoring is often acclaimed to be the preferred method of adherence measure, the present study found that data were difficult to collect for the long monitoring period appropriate for the study of this chronic condition and might be sensitive to study reactivity bias. No gold-standard method for measuring adherence currently exists and it is likely that the practicalities of data collection will continue to govern what is ultimately chosen as an appropriate measure of adherence for each individual study. Unfortunately, whilst a standardised and accurate measure for adherence remains undefined, studies will continue to produce heterogeneous adherence results. Equally, multiple methods of adherence measurement used in parallel to quantify and classify adherence may maximise precision of adherence estimates and facilitate comparisons between studies, the effect that multiple measures of adherence have on patient behaviour is unknown. AcknowledgementsThe present paper presents independent research commissioned by the National Institute for Health Research (NIHR) under its Research for Patient Benefit (RfPB) Programme (Grant Reference Number PB-PG-1207-14119). The views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health. Neither the sponsor nor funding organization had any role in the design or conduct of this research.Alcon Laboratories Inc., Fort Worth, TX, USA, supplied the Travalert? Dosing Aid but the organization had no role in the design or conduct of this research.Conflict of interest statementThe authors declare that there are no conflicts of interest. References ADDIN EN.REFLIST 1.Burke LE, Dunbar-Jacob JM, Hill MN. Compliance with cardiovascular disease prevention strategies: a review of the research. Annals of behavioral medicine : a publication of the Society of Behavioral Medicine. 1997; 19: 239-263.2.Waterman H, Evans JR, Gray TA, et al. Interventions for improving adherence to ocular hypotensive therapy. The Cochrane database of systematic reviews. 2013; 4: CD006132.3.DiMatteo MR. Variations in patients' adherence to medical recommendations: a quantitative review of 50 years of research. Med Care. 2004; 42: 200-209.4.Kass MA, Meltzer DW, Gordon M, et al. Compliance with topical pilocarpine treatment. Am J Ophthalmol. 1986; 101: 515-523.5.Choo PW, Rand CS, Inui TS, et al. Validation of patient reports, automated pharmacy records, and pill counts with electronic monitoring of adherence to antihypertensive therapy. Med Care. 1999; 37: 846-857.6.Kass MA, Gordon M, Meltzer DW. Can ophthalmologists correctly identify patients defaulting from pilocarpine therapy? Am J Ophthalmol. 1986; 101: 524-530.7.Friedman DS, Hahn SR, Gelb L, et al. Doctor-patient communication, health-related beliefs, and adherence in glaucoma results from the Glaucoma Adherence and Persistency Study. Ophthalmology. 2008; 115: 1320-1327 .8.Gilbert JR, Evans CE, Haynes RB, et al. Predicting compliance with a regimen of digoxin therapy in family practice. Canadian Medical Association journal. 1980; 123: 119-122.9.Gray TA, Orton LC, Henson D, et al. Interventions for improving adherence to ocular hypotensive therapy. The Cochrane database of systematic reviews. 2009: CD006132.10.Litcher-Kelly L, Kellerman Q, Hanauer SB, et al. Feasibility and utility of an electronic diary to assess self-report symptoms in patients with inflammatory bowel disease. Annals of behavioral medicine : a publication of the Society of Behavioral Medicine. 2007; 33: 207-212.11.Diaz E, Levine HB, Sullivan MC, et al. Use of the Medication Event Monitoring System to estimate medication compliance in patients with schizophrenia. Journal of psychiatry & neuroscience : JPN. 2001; 26: 325-329.12.Cook P, Schmiege S, McClean M, et al. Practical and analytic issues in the electronic assessment of adherence. Western journal of nursing research. 2012; 34: 598-620.13.Richardson C, Brunton L, Olleveant N, et al. A study to assess the feasibility of undertaking a randomized controlled trial of adherence with eye drops in glaucoma patients. Patient preference and adherence. 2013; 7: 1025-1039.14.Ajit RR, Fenerty CH, Henson DB. Patterns and rate of adherence to glaucoma therapy using an electronic dosing aid. Eye (Lond). 2010; 24: 1338-1343.15.Cate H, Bhattacharya D, Clark A, et al. Patterns of adherence behaviour for patients with glaucoma. Eye. 2013.16.Blaschke TF, Osterberg L, Vrijens B, et al. Adherence to medications: insights arising from studies on the unreliable link between prescribed and actual drug dosing histories. Annual review of pharmacology and toxicology. 2012; 52: 275-301.17.Sackett D, Snow J. Magnitude and Measurement of Compliance In: Haynes B, Wayne Taylor D, Sacket D, (eds.). Compliance in Healthcare. Baltimore and London: The John Hopkins University Press, 1979.18.Olthoff CM, Schouten JS, van de Borne BW, et al. Noncompliance with ocular hypotensive treatment in patients with glaucoma or ocular hypertension an evidence-based review. Ophthalmology. 2005; 112: 953-961.19.Sorensen L, Stokes JA, Purdie DM, et al. Medication management at home: medication-related risk factors associated with poor health outcomes. Age and ageing. 2005; 34: 626-632.20.Leske MC, Heijl A, Hussein M, et al. Factors for glaucoma progression and the effect of treatment: the early manifest glaucoma trial. Arch Ophthalmol. 2003; 121: 48-56.21.Heijl A, Leske MC, Bengtsson B, et al. Reduction of intraocular pressure and glaucoma progression: results from the Early Manifest Glaucoma Trial. Arch Ophthalmol. 2002; 120: 1268-1279.22.Cate H, Bhattacharya D, Clark A, et al. Protocol for a randomised controlled trial to estimate the effects and costs of a patient centred educational intervention in glaucoma management. BMC Ophthalmol. 2012; 12: 57.23.Cate H. A pilot study to assess the feasibility of using the Travalert dosing aid to measure adherence. University of East Anglia, School of Pharmacy: University of East Anglia, 2011, p. 127.24.Morisky DE, Green LW, Levine DM. Concurrent and predictive validity of a self-reported measure of medication adherence. Med Care. 1986; 24: 67-74.25.Friedman DS, Quigley HA, Gelb L, et al. Using pharmacy claims data to study adherence to glaucoma medications: methodology and findings of the Glaucoma Adherence and Persistency Study (GAPS). Invest Ophthalmol Vis Sci. 2007; 48: 5052-5057.26.Fiscella RG, Green A, Patuszynski DH, et al. Medical therapy cost considerations for glaucoma. Am J Ophthalmol. 2003; 136: 18-25.27.Cate H, Bhattacharya D, Clark A, et al. Improving adherence to glaucoma medication: a randomised controlled trial of a patient-centred intervention (The Norwich Adherence Glaucoma Study). BMC Ophthalmol. 2014; 14: 32.28.Landis JR, Koch GG. The measurement of observer agreement for categorical data. Biometrics. 1977; 33: 159-174.29.Gray TA, Fenerty C, Harper R, et al. Individualised patient care as an adjunct to standard care for promoting adherence to ocular hypotensive therapy: an exploratory randomised controlled trial. Eye (Lond). 2012; 26: 407-417.30.McCowan C, Wang S, Thompson AM, et al. The value of high adherence to tamoxifen in women with breast cancer: a community-based cohort study. Br J Cancer. 2013; 109: 1172-1180.31.Flynn RW, MacDonald TM, Murray GD, et al. Persistence, adherence and outcomes with antiplatelet regimens following cerebral infarction in the Tayside Stroke Cohort. Cerebrovascular diseases. 2012; 33: 190-197.32.Taylor A, Chen LC, Smith MD. Adherence to inhaled corticosteroids by asthmatic patients: measurement and modelling. International journal of clinical pharmacy. 2014; 36: 112-119.33.Langley CA, Bush J. The Aston Medication Adherence Study: mapping the adherence patterns of an inner-city population. International journal of clinical pharmacy. 2014; 36: 202-211.34.Okeke CO, Quigley HA, Jampel HD, et al. Adherence with topical glaucoma medication monitored electronically the Travatan Dosing Aid study. Ophthalmology. 2009; 116: 191-199.35.Friedman DS, Jampel HD, Congdon NG, et al. The TRAVATAN Dosing Aid accurately records when drops are taken. Am J Ophthalmol. 2007; 143: 699-701.36.Lacey J, Cate H, Broadway DC. Barriers to adherence with glaucoma medications: a qualitative research study. Eye (Lond). 2009; 23: 924-932.37.Gadkari AS, McHorney CA. Unintentional non-adherence to chronic prescription medications: how unintentional is it really? BMC Health Serv Res. 2012; 12: 98.38.Mankarious E, Kothe E. A meta-analysis of the effects of measuring theory of planned behaviour constructs on behaviour within prospective studies. Health psychology review: 2014, (accessed 08 July 2014).Reason for missing dataNumber of participants with missing data*MMAS Questionnaire #FMD Questionnaire Prescribing record~TDA2 months8 months2 months8 monthsTotal period2 months8 monthsQuestionnaire or ~TDA not returned / used / fully completed by patient1713118-812Data not provided by health centre----49--Device / battery failure-----1232Participant withdrawn or stopped or changed treatment118118241948Lost to follow-up / Deceased2222222Total Missing20 (10%)33(16%)14(7%)28(13%)75(36%)41(20%)94(45%)*MMAS (Morisky Medication Adherence Score)#FMD (Frequency Missed Dose)~TDA (Travalert Dosing Aid)Table 1. Reason for missing data compared between measures. Agreement between month 2 and month 8Kappa (p)*MMASDichotomised0.402 (p<0.0001)n = 166Month 8Non-AdherentAdherentMonth 2Non-Adherent3312Adherent3388#FMDDichotomised0.556 (p<0.0001)n=172Month 8Non-AdherentAdherentMonth 2Non-Adherent4610Adherent2690~TDA Dichotomised0.629 (p<0.0001)n=114Month 8Non-AdherentAdherentMonth 2Non-Adherent4211Adherent1051* MMAS (Morisky Medication Adherence Score)# FMD (Frequency Missed Dose)~ TDA (Travalert Dosing Aid)Table 2.Participant adherence status at month two compared with month eight.Adherence score % (n)Agreement between measures Kappa (P)*MMAS#FMD*MMASDichotomisedTotal n=18872.3(136)--#FMDDichotomisedTotal n=19467.5(131)0.632 (p<0.0001)n=186-Non- AdherentAdherentNon-Adherent4219Adherent10115~TDA DichotomisedTotal n=16753.3(89)0.117 (p=0.124)n=1560.233 (p=0.002)n=161Non- AdherentAdherentNon- AdherentAdherentNon-Adherent2521Non-Adherent3319Adherent4565Adherent4168* MMAS (Morisky Medication Adherence Score)# FMD (Frequency Missed Dose)~ TDA (Travalert Dosing Aid)Table 3.Agreement between, MMAS, FMDA and TDA dichotomised score at two months.Adherence score % (n)Agreement between measures Kappa (P)*MMAS#FMD*MMASDichotomisedTotal n=17560.0(105)--#FMDDichotomisedTotal n=18057.2(103)0.724 (p<0.0001)n=172-Non- AdherentAdherentNon-Adherent599Adherent1490~TDA DichotomisedTotal n=11454.4(62)0.180 (p=0.059)n=1090.289 (p=0.002)n=111Non- AdherentAdherentNon- AdherentAdherentNon-Adherent2519Non-Adherent3019Adherent2540Adherent2042* MMAS (Morisky Medication Adherence Score)# FMD (Frequency Missed Dose)~ TDA (Travalert Dosing Aid)Table 4.Agreement between, MMAS, FMD, and TDA dichotomised scores at eight months. ................
................
In order to avoid copyright disputes, this page is only a partial summary.
To fulfill the demand for quickly locating and searching documents.
It is intelligent file search solution for home and business.
Related searches
- title page of lab report
- apa 6 title page format
- apa title page template
- turabian title page template
- apa title page generator
- apa title page template word
- title page example apa format
- army title page format
- research title page example
- apa 7th edition title page format
- apa 7 title page example
- apa 7th edition title page sample