Identifikation af non-kompliante hypertonikere - Udvikling af screeningsredskab ved grafiske analyser

174 Pages·2008·0.84 MB·Danish

Identifikation af non-kompliante hypertonikere

Udvikling af screeningsredskab ved grafisk analyse

Speciale udarbejdet af
Marianne Maibøll & Marianne Agergaard
Kandidatuddannelsen i Folkesundhedsvidenskab
Københavns Universitet

Vejledere
Lektor Svend Kreiner, Institut for Folkesundhedsvidenskab, Københavns Universitet
Cand.scient.san.publ. Pernille Dam, Pharmakon

Januar 2008

1
Forord

Hillerød, januar 2008

Dette speciale er udarbejdet i efteråret 2007. Data er stillet til rådighed af Pharmakon, der har
stået for spørgeskemaudarbejdelse og dataindsamling. I forbindelse med metodevalg og vink-
ling af opgaven har vi haft frie hænder.

Der takkes for uvurderlig hjælp og støtte fra familie, venner og ansatte i afdeling APS på Phar-
makon. Især takkes vejlederne Svend Kreiner og Pernille Dam for inspiration og optimisme.

God læselyst.

Marianne Maibøll Marianne Agergaard

Opgavens omfang svarer til 118 normalsider
2
Resume
Lægemiddel non-compliance opstår, når patienten ikke tager medicinen som ordineret. Non-
compliance anses for en af de vigtigste årsager til ukontrolleret hypertension, med øget risiko
for kardiovaskulære komplikationer til følge. Det har vist sig vanskeligt at screene for non-
compliance, idet alle kendte metoder har svagheder.

Formålet med opgaven er at udvikle et simpelt, præcist og validt screeningsredskab, der kan
anvendes i den primære sundhedssektor til at identificere non-kompliante hypertensionspatien-
ter.

Udgangspunktet for analysen er spørgeskemadata fra 1421 hypertensionspatienter samt data
fra patienternes medicinprofil (PEM; n = 182) og elektroniske medicinbeholdere (MEMS; n =
33). Analyserne foretages ved brug af grafiske Rasch-modeller og omfatter indledningsvis en
skalavalidering af fire spørgsmålsgrupper. Heraf findes henholdsvis tre og fem valide og skaler-
bare skalaer. Skalaerne anvendes i to efterfølgende multivariate multiple regressionsanalyser,
hvor der inddrages henholdsvis 28 og 29 variable.

Spørgsmålet ”Lå dit høje blodtryk over 140 mmHg sidste gang, du fik det målt?” (´systolisk BT´)
viser sig at være central i kraft af dens korrelation med PEM og MEMS. De inddragne skalaer er
alle signifikant forbundne og korrelerer med PEM via skalaen ´utilsigtet non-compliance´. Denne
skala består af fem spørgsmål og vedrører patientens tilbøjelighed til at glemme indtagelsen af
medicin. Desuden vises, at det kan være relevant at inddrage skalaen vedrørende bekymringer
relateret til medicinindtagelsen (´medicinsk bekymring´) og skalaen vedrørende situationer, hvor
patienten fravælger at følge lægemiddelordinationerne (’tilsigtet non-compliance’). På baggrund
af de forskellige datakilder og antallet af variable inddraget i analyserne vurderes det, at scree-
ningsredskabet er validt.

Det konkluderes, at et simpelt og præcist screeningsredskab består af variablen ´systolisk BT´
og skalaen ´utilsigtet non-compliance´. Dette redskab kan, hvis det findes indholdsmæssigt re-
levant og realiserbart, suppleres med skalaerne ´medicinsk bekymring´ og/eller ´tilsigtet non-
compliance´.

3
Abstract
Identification of non-adherent hypertensive patients – Development of a screening
instrument using graphical models.

Introduction: Medical non-compliance occur when patients do not take their medicines as
directed. Poor compliance with antihypertensive medication is assumed to be an important
reason for unsatisfactory control of blood pressure, which may result in severe cardiovascular
complications. It is proven difficult to detect non-compliance as all known methods have
weaknesses.

The aim of the present study is developing a simple, precise and valid screening instrument for
use in primary health care to identify hypertensive patients, who do not follow the prescriptions.

Material and methods: The data consists of questionnaires obtained from 1421 hypertensive
patients, together with pharmacy refill records (PEM; n = 182) and electronic monitors (MEMS;
n = 33). The analysis is carried out using graphical Rasch-models and consist of validation of
four multi-item scales and two regression analysis of respectively 28 and 29 variables. The

Results: The regression analyses reveals strong significant correlations between the self-
reported variable ´systolic BP´ (“Did your systolic blood pressure exceed 140 mmHg the last
time, it was measured?”) and the measures of PEM and MEMS. The validated scales correlates
with compliance according to PEM. The scale ´unintentional non-compliance´ consists of five
questions concerning medication lapse. This scale connects to ´systolic BP´ in the graphical
models. Furthermore it seems relevant to include either a scale regarding ´medical concerns´
and/or a scale describing situations in which the patient chooses to violate the prescriptions
(´intentional non-compliance´). Due to the different data sources and many included variables
related to compliance-behaviour, the analysis succeeded in creating a validated tool for
screening patients.

Conclusions: It can be concluded, that a simple and precise screening instrument should
consist of the variable ´systolic BP´ and the scale ´unintentional non-compliance´. In case of
relevance, including scales concerning ´medical concerns´ and/or ´intentional non-compliance´
can increase the sensitivity of the instrument.
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Indholdsfortegnelse

Forord..........................................................................................................................................................2
Resume........................................................................................................................................................3
Abstract.......................................................................................................................................................4
Liste over tabeller.......................................................................................................................................9
Liste over figurer......................................................................................................................................10
1 Indledning.........................................................................................................................................11
2 Problemformulering.........................................................................................................................14
2.1 Begrebsafklaring i relation til problemformuleringen.................................................................15
3 Specialets opbygning......................................................................................................................16
4 Introduktion til begrebet non-compliance.....................................................................................17
4.1 Compliance og non-compliance................................................................................................17
4.2 Non-compliance i relation til hypertension................................................................................17
4.3 Typer af non-compliance...........................................................................................................18
4.3.1 Tilsigtet non-compliance.......................................................................................................19
4.3.2 Utilsigtet non-compliance......................................................................................................19
4.4 Hvornår er en patient non-kompliant?.......................................................................................19
4.5 Metoder til screening for non-compliance.................................................................................21
4.5.1 Spørgeskema........................................................................................................................24
4.5.2 Personlig Elektronisk Medicinprofil (PEM)............................................................................25
4.5.3 Medication Event Monitoring System (MEMS).....................................................................26
4.5.4 Afsluttende kommentarer til screeningsmetoder..................................................................28
4.6 Årsager til non-compliance........................................................................................................28
4.6.1 Concordance (medindflydelse).............................................................................................30
4.6.2 Handlekompetence (´self-efficacy´)......................................................................................31
4.6.3 Egenindsats (´locus of control´ og ´self management´)........................................................31
4.7 Hvordan øges compliance-graden?..........................................................................................31
4.8 Opsummering............................................................................................................................33
5 Projektet ´Sikker og effektiv medicinbrug for brugere af blodtryksmedicin´............................34
5.1 Udvælgelse af deltagere...........................................................................................................34
5.2 Dataindsamling i projektforløbet...............................................................................................35
6 Skalavaliditet og skalerbarhed.......................................................................................................36
6.1 Validitet......................................................................................................................................36
6.1.1 Begrebsvaliditet (´construct validity´)....................................................................................36
6.1.2 Kriterievaliditet (´criterion validity´)........................................................................................37
6.1.3 Sensitivitet og ´responsiveness´...........................................................................................37
6.1.4 Indholdsvaliditet (´content validity´ og ’face validity’)............................................................37
6.2 Skalerbarhed.............................................................................................................................38
6.2.1 Reliabilitet.............................................................................................................................38
6.2.2 Cronbach’s alfa (α)...............................................................................................................38
6.2.3 Objektivitet............................................................................................................................39
6.2.4 Sufficiens..............................................................................................................................39
6.2.5 Generaliserbarhed................................................................................................................39
6.3 Afsluttende kommentar til validering og skalerbarhed..............................................................39
7 Item response theory (IRT).............................................................................................................41
7.1 Den latente variabel og sum-scoren.........................................................................................41
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7.2 Egenskaber ved IRT.................................................................................................................42
7.3 Antagelser for IRT-modellerne..................................................................................................42
7.3.1 Lokal uafhængighed.............................................................................................................43
7.3.2 Unidimensionalitet................................................................................................................43
7.3.3 Fravær af DIF........................................................................................................................43
7.3.4 Monotonitet...........................................................................................................................44
7.4 Rasch modeller.........................................................................................................................44
7.4.1 Grafiske Rasch modeller (GRM)...........................................................................................45
7.4.2 Grafiske loglineære Rasch modeller (GLLRM).....................................................................45
7.4.3 Opsamling for de anvendte IRT-modeller.............................................................................46
8 Grafiske modeller.............................................................................................................................47
8.1.1 Den rekursive struktur...........................................................................................................47
8.1.2 Betinget uafhængighed.........................................................................................................47
8.1.3 Separations egenskaber.......................................................................................................47
9 Metode..............................................................................................................................................48
9.1 Indledende databehandling.......................................................................................................50
9.1.1 Udvælgelse af spørgeskemavariable...................................................................................50
9.1.2 PEM-data..............................................................................................................................57
9.1.3 MEMS-data...........................................................................................................................59
9.1.4 Frasortering af cases............................................................................................................61
9.1.5 Kategorisering af variable.....................................................................................................61
9.2 Introduktion til den statistiske analyse......................................................................................63
9.2.1 Egenskaber ved DIGRAM....................................................................................................63
9.3 Skalavalidering..........................................................................................................................65
9.3.1 Kvalitetskriterier for skalaerne..............................................................................................65
9.3.2 Fremgangsmåde...................................................................................................................66
9.3.3 Dannelse af skala med personestimater..............................................................................70
9.4 Multivariat analyse....................................................................................................................71
9.4.1 Definition af model................................................................................................................71
9.4.2 Analysestrategi.....................................................................................................................71
9.4.3 Endelig model.......................................................................................................................73
9.5 Opsummering af metoden.........................................................................................................74
10 Resultater.........................................................................................................................................75
10.1 Deskriptiv statistik.....................................................................................................................76
10.1.1 De subjektive data: Spørgeskemavariable.......................................................................76
10.1.2 De objektive data: PEM og MEMS...................................................................................79
10.2 Skalavalidering..........................................................................................................................82
10.2.1 Problemer med medicinen...............................................................................................83
10.2.2 Erfaringer med medicinen................................................................................................87
10.2.3 Din psykiske trivsel...........................................................................................................93
10.2.4 Din brug af medicin: Analyse 1.........................................................................................95
10.2.5 Din brug af medicin: Analyse 2.......................................................................................100
10.2.6 Opsummering af resultater fra skalavalideringen...........................................................107
10.3 Deskriptiv statistik: Skalaer.....................................................................................................109
10.4 Multivariat analyse..................................................................................................................113
10.4.1 Analyse 1........................................................................................................................114
10.4.2 Analyse 2........................................................................................................................118
10.5 Opsummering af resultater fra den grafiske regressionsanalyse...........................................122
11 Diskussion af datamateriale og metodevalg...............................................................................123
11.1 Udvælgelse af spørgeskemavariable......................................................................................123
11.1.1 Prioritering af variable....................................................................................................123
11.1.2 De eksogene variable som mulige confoundere............................................................124
11.1.3 Variablene ´systolisk BT´ og ´diastolisk BT´...................................................................124
11.1.4 Begrænsninger på grund af frasorteringen af variable...................................................126
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11.1.5 Afsluttende kommentarer til udvælgelsen af variable....................................................126
11.2 Direkte og indirekte formulerede spørgsmål...........................................................................127
11.3 Variabel- og skalanavne..........................................................................................................128
11.4 Metodiske valg........................................................................................................................128
11.4.1 Antagelser i opgaven......................................................................................................128
11.4.2 Udelukkelse af svarkategorien ´Ikke relevant´...............................................................129
11.4.3 Selektionsbias og bortfald i undersøgelsen...................................................................129
11.5 Delkonklusion om datamateriale og metodevalg....................................................................131
12 Diskussion af skalavalideringens resultater...............................................................................132
12.1 Fortolkning af γ-koefficienterne..............................................................................................132
12.2 Logikken bag de lokale afhængigheder..................................................................................132
12.2.1 Homogenitet og lokal afhængighed................................................................................132
12.2.2 ’Response dependence’.................................................................................................133
12.2.3 Afsluttende kommentar til lokal afhængighed................................................................134
12.3 Betydningen af DIF.................................................................................................................134
12.4 Skalaernes validitet og skalerbarhed......................................................................................135
12.4.1 Begrebsvaliditet..............................................................................................................135
12.4.2 Kriterievaliditet................................................................................................................135
12.4.3 Sensitivitet......................................................................................................................136
12.4.4 Reliabilitet.......................................................................................................................136
12.4.5 Generaliserbarhed..........................................................................................................137
12.5 Afsluttende kommentarer til skalavalideringen.......................................................................137
12.6 Dimensioner af non-compliance.............................................................................................137
12.6.1 ´Utilsigtet non-compliance´.............................................................................................138
12.6.2 ´Tilsigtet non-compliance´..............................................................................................139
12.6.3 ´Handlekompetence´......................................................................................................139
12.6.4 ´Overskud´, ´praktiske problemer´ og ´medicinsk bekymring´ som supplement til
´handlekompetence´........................................................................................................................140
12.6.5 Under- og overmedicinering...........................................................................................142
12.7 Delkonklusion for skalaernes compliance-dimensioner..........................................................143
13 Diskussion af de multivariate analyser.......................................................................................145
13.1 Tolkning af resultater for multivariat analyse 1.......................................................................145
13.1.1 Enkelt-variable som compliance-variable.......................................................................145
13.1.2 MEMS compliance-variable............................................................................................146
13.1.3 PEM og skala compliance-variable................................................................................148
13.1.4 Opsummering af analyse 1............................................................................................150
13.2 Tolkning af resultater for multivariat analyse 2.......................................................................151
13.2.1 Enkelt-variable som compliance-variable.......................................................................151
13.2.2 MEMS compliance-variable............................................................................................151
13.2.3 PEM og skala compliance-variable................................................................................151
13.2.4 Opsummering af analyse 2............................................................................................152
13.3 Validiteten af de multivariate analyser....................................................................................153
13.3.1 Begrebsvaliditet for non-compliance..............................................................................153
13.3.2 Variablene kriterievalideres indbyrdes...........................................................................153
13.3.3 Selektionsbias’ påvirkning af validiteten.........................................................................153
13.3.4 Skalaernes sufficiens......................................................................................................154
13.4 Afsluttende kommentarer til den mulitvariate analyse............................................................155
14 Udvikling af screeningsredskab...................................................................................................156
14.1 Compliance variablenes relevans...........................................................................................156
14.2 Det simple og præcise screeningsredskab.............................................................................158
14.3 Screeningsredskabet..............................................................................................................160
14.4 Den praktiske anvendelse af screeningsredskabet................................................................161
15 Konklusion.....................................................................................................................................163
16 Perspektivering..............................................................................................................................164
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17 Anvendte forkortelser og begreber..............................................................................................166
18 Litteraturliste..................................................................................................................................169
19 Bilag................................................................................................................................................173

8
Liste over tabeller

Tabel 1: Screeningsmetoder til non-compliance........................................................................................22
Tabel 2: Udvalgte prædiktorer for non-compliance for hypertensionspatienter.........................................29
Tabel 3: Oversigt over IRT-modellernes egenskaber................................................................................46
Tabel 4: Udvalgte spørgeskemavariable....................................................................................................51
Tabel 5: Frasorterede spørgeskemavariable.............................................................................................56
Tabel 6: Fordeling af eksogene variable....................................................................................................76
Tabel 7: Fordeling af prædiktorvariable......................................................................................................77
Tabel 8: Krydstabel for variablene ´systolisk BT´ og ´diastolisk BT´..........................................................78
Tabel 9: Fordeling af compliance-variablene fra spørgeskemaerne..........................................................79
Tabel 10: Fordeling af PEM- og MEMS-data.............................................................................................80
Tabel 11: Fordeling af de kategoriserede PEM- og MEMS-data...............................................................81
Tabel 12: Fordelingen af besvarelser for ´problemer med medicinen´......................................................83
Tabel 13: Fordelingen af besvarelser for ´erfaringer med medicinen´.......................................................87
Tabel 14: Fordelingen af besvarelser for ´din psykiske trivsel´..................................................................93
Tabel 15: Fordelingen af besvarelser for ´din brug af medicin´..................................................................95
Tabel 16: Fordelingen af scorerne for skalaen ´utilsigtet non-compliance´.............................................109
Tabel 17: Fordelingen af scorerne for skalaen ´tilsigtet non-compliance´...............................................109
Tabel 18: Fordelingen af scorerne for skalaen ´handlekompetence´.......................................................110
Tabel 19: Fordelingen af besvarelserne for enkelt-variablene.................................................................110
Tabel 20: Fordelingen af scorerne for skalaen ´overskud´.......................................................................111
Tabel 21: Fordelingen af scorerne for skalaen ´praktiske problemer´.....................................................111
Tabel 22: Fordelingen af scorerne for skalaen ´medicinsk bekymring´...................................................112
Tabel 23: Krydstabel for PEM og score for ´tilsigtet non-compliance´.....................................................149

9
Liste over figurer

Figur 1: Typer af non-compliance [efter Barber, 2002]..............................................................................18
Figur 2: Persistence for undersøgelsespopulationen beregnet vha. MEMS..............................................27
Figur 3: MEMS-målene for alle cases (n = 33)...........................................................................................80
Figur 4: Skalaen ´utilsigtet non-compliance´..............................................................................................90
Figur 5: Skalaen ´tilsigtet non-compliance´................................................................................................92
Figur 6: Skalaen ´handlekompetence´.......................................................................................................99
Figur 7: Skalaen ´overskud´.....................................................................................................................103
Figur 8: Skalaen ´praktiske problemer´....................................................................................................104
Figur 9: Skalaen ´medicinsk bekymring´..................................................................................................106
Figur 10: Komplet model for analyse 1.....................................................................................................116
Figur 11: Selekteret model for analyse 1..................................................................................................117
Figur 12: Komplet model for analyse 2.....................................................................................................120
Figur 13: Selekteret model for analyse 2..................................................................................................121
Figur 14: Illustration af screeningsredskabet............................................................................................160

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