FA-MA105
Medicatiebeleid
Samenvatting
,Inhoud
Algemeen ........................................................................................................................................................ 5
Leerdoelen....................................................................................................................................................... 6
Schriftelijk tentamen ................................................................................................................................... 6
Geneesmiddelonderzoek ................................................................................................................................ 7
Waar speelt evidence een rol...................................................................................................................... 7
Bijwerkingen ................................................................................................................................................ 8
Dilemma ...................................................................................................................................................... 8
Patiëntpopulatie .......................................................................................................................................... 8
Type I en II fouten ....................................................................................................................................... 8
Het zorginstituut Nederland (ZIN) ............................................................................................................... 9
Evidence based medicine .......................................................................................................................... 10
Coronavaccin ............................................................................................................................................. 10
Onderzoeksopzet (study-design)................................................................................................................... 11
Randomised clinical trial (RCT) ...................................................................................................................... 12
Randomisatie............................................................................................................................................. 12
Blok randomisatie/ stratificeren 1:1 ratio ............................................................................................. 12
Gestratificeerde randomisatie .............................................................................................................. 12
Observationeel onderzoek ............................................................................................................................ 13
Cohort onderzoek...................................................................................................................................... 13
Case-control onderzoek ............................................................................................................................ 14
Cohort Vs. Case-control............................................................................................................................. 14
Analyse ...................................................................................................................................................... 15
Propensity score ........................................................................................................................................ 15
Schatting propensity-score.................................................................................................................... 15
Gebruik propensity score ...................................................................................................................... 15
Voordelen propensity score .................................................................................................................. 16
Nadelen propensity score ..................................................................................................................... 16
Rapporteren .......................................................................................................................................... 16
Case report/ Case series & Case-crossover studie ........................................................................................ 17
Case report/ Case series ............................................................................................................................ 17
Case-crossover studie................................................................................................................................ 17
Effectmaten & effectmodificatie in geneesmiddelonderzoek ...................................................................... 20
Effectmaten cohortonderzoek .................................................................................................................. 20
Effectmaten case-control onderzoek ........................................................................................................ 21
Effectmodificatie ....................................................................................................................................... 22
Primaire en secundaire eindpunten .......................................................................................................... 22
Composite outcome: samengestelde uitkomst ........................................................................................ 22
Kaplan-Meier curve ................................................................................................................................... 23
2
,Bias & Confounding ....................................................................................................................................... 25
Selectiebias................................................................................................................................................ 25
Informatiebias ........................................................................................................................................... 25
Confounding .............................................................................................................................................. 25
Corrigeren voor confounding – COX-regressie...................................................................................... 25
Voorkomen van confounding – matching, restrictie, stratificatie ........................................................ 26
Misclassificatie .......................................................................................................................................... 26
Immeasurable time bias ............................................................................................................................ 26
Immortal time bias .................................................................................................................................... 27
Time-window bias ..................................................................................................................................... 27
Time-lag bias ............................................................................................................................................. 27
Analyse .......................................................................................................................................................... 28
Intention to treat analyse.......................................................................................................................... 28
Per protocol analyse.................................................................................................................................. 28
Interim analyse .......................................................................................................................................... 29
Wetenschappelijke integriteit ....................................................................................................................... 30
Vergoedingsbeleid......................................................................................................................................... 33
Modelleren .................................................................................................................................................... 35
Markov model ........................................................................................................................................... 35
A. Vaststellen van de modelstructuur .............................................................................................. 35
B. Vaststellen van de transitiekansen ............................................................................................... 36
C. Vaststellen van de kosten en utiliteiten ....................................................................................... 36
D. Vaststellen van de behandeleffecten ........................................................................................... 37
E. Bouwen van de verdeling van patiënten (de Markov trace) gedurende de tijdshorizon voor
vergelijkende behandeling .................................................................................................................... 37
F. Bouwen van de verdeling van patiënten gedurende de tijdshorizon voor de nieuwe behandeling
38
G. Eventueel verdisconteren ............................................................................................................. 38
H. Berekenen van de kosten voor de oude en nieuwe behandeling ................................................ 39
I. Berekenen van de ICER ................................................................................................................. 39
J. Uitvoeren van de deterministische sensitiviteitsanalyse ............................................................. 40
K. Uitvoeren van de probabilistische sensitiviteitsanalyse ............................................................... 40
L. Uitvoeren van aanvullende analyses, zoals een cost-effectiveness acceptability frontier,
scenario analyses en value of information analyses ............................................................................. 42
Kritisch beoordelen observationele studies .................................................................................................. 44
De kwaliteit van individuele studies beoordelen ...................................................................................... 44
De beoordeling door ZIN ........................................................................................................................... 44
Farmacotherapeutische beoordeling bij ZIN ......................................................................................... 44
Farmaco-economische beoordeling bij ZIN........................................................................................... 44
Eindoordeel van ZIN .............................................................................................................................. 47
3
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Medicatiebeleid
Samenvatting
,Inhoud
Algemeen ........................................................................................................................................................ 5
Leerdoelen....................................................................................................................................................... 6
Schriftelijk tentamen ................................................................................................................................... 6
Geneesmiddelonderzoek ................................................................................................................................ 7
Waar speelt evidence een rol...................................................................................................................... 7
Bijwerkingen ................................................................................................................................................ 8
Dilemma ...................................................................................................................................................... 8
Patiëntpopulatie .......................................................................................................................................... 8
Type I en II fouten ....................................................................................................................................... 8
Het zorginstituut Nederland (ZIN) ............................................................................................................... 9
Evidence based medicine .......................................................................................................................... 10
Coronavaccin ............................................................................................................................................. 10
Onderzoeksopzet (study-design)................................................................................................................... 11
Randomised clinical trial (RCT) ...................................................................................................................... 12
Randomisatie............................................................................................................................................. 12
Blok randomisatie/ stratificeren 1:1 ratio ............................................................................................. 12
Gestratificeerde randomisatie .............................................................................................................. 12
Observationeel onderzoek ............................................................................................................................ 13
Cohort onderzoek...................................................................................................................................... 13
Case-control onderzoek ............................................................................................................................ 14
Cohort Vs. Case-control............................................................................................................................. 14
Analyse ...................................................................................................................................................... 15
Propensity score ........................................................................................................................................ 15
Schatting propensity-score.................................................................................................................... 15
Gebruik propensity score ...................................................................................................................... 15
Voordelen propensity score .................................................................................................................. 16
Nadelen propensity score ..................................................................................................................... 16
Rapporteren .......................................................................................................................................... 16
Case report/ Case series & Case-crossover studie ........................................................................................ 17
Case report/ Case series ............................................................................................................................ 17
Case-crossover studie................................................................................................................................ 17
Effectmaten & effectmodificatie in geneesmiddelonderzoek ...................................................................... 20
Effectmaten cohortonderzoek .................................................................................................................. 20
Effectmaten case-control onderzoek ........................................................................................................ 21
Effectmodificatie ....................................................................................................................................... 22
Primaire en secundaire eindpunten .......................................................................................................... 22
Composite outcome: samengestelde uitkomst ........................................................................................ 22
Kaplan-Meier curve ................................................................................................................................... 23
2
,Bias & Confounding ....................................................................................................................................... 25
Selectiebias................................................................................................................................................ 25
Informatiebias ........................................................................................................................................... 25
Confounding .............................................................................................................................................. 25
Corrigeren voor confounding – COX-regressie...................................................................................... 25
Voorkomen van confounding – matching, restrictie, stratificatie ........................................................ 26
Misclassificatie .......................................................................................................................................... 26
Immeasurable time bias ............................................................................................................................ 26
Immortal time bias .................................................................................................................................... 27
Time-window bias ..................................................................................................................................... 27
Time-lag bias ............................................................................................................................................. 27
Analyse .......................................................................................................................................................... 28
Intention to treat analyse.......................................................................................................................... 28
Per protocol analyse.................................................................................................................................. 28
Interim analyse .......................................................................................................................................... 29
Wetenschappelijke integriteit ....................................................................................................................... 30
Vergoedingsbeleid......................................................................................................................................... 33
Modelleren .................................................................................................................................................... 35
Markov model ........................................................................................................................................... 35
A. Vaststellen van de modelstructuur .............................................................................................. 35
B. Vaststellen van de transitiekansen ............................................................................................... 36
C. Vaststellen van de kosten en utiliteiten ....................................................................................... 36
D. Vaststellen van de behandeleffecten ........................................................................................... 37
E. Bouwen van de verdeling van patiënten (de Markov trace) gedurende de tijdshorizon voor
vergelijkende behandeling .................................................................................................................... 37
F. Bouwen van de verdeling van patiënten gedurende de tijdshorizon voor de nieuwe behandeling
38
G. Eventueel verdisconteren ............................................................................................................. 38
H. Berekenen van de kosten voor de oude en nieuwe behandeling ................................................ 39
I. Berekenen van de ICER ................................................................................................................. 39
J. Uitvoeren van de deterministische sensitiviteitsanalyse ............................................................. 40
K. Uitvoeren van de probabilistische sensitiviteitsanalyse ............................................................... 40
L. Uitvoeren van aanvullende analyses, zoals een cost-effectiveness acceptability frontier,
scenario analyses en value of information analyses ............................................................................. 42
Kritisch beoordelen observationele studies .................................................................................................. 44
De kwaliteit van individuele studies beoordelen ...................................................................................... 44
De beoordeling door ZIN ........................................................................................................................... 44
Farmacotherapeutische beoordeling bij ZIN ......................................................................................... 44
Farmaco-economische beoordeling bij ZIN........................................................................................... 44
Eindoordeel van ZIN .............................................................................................................................. 47
3
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