Cognitive enhancers for the treatment of Alzheimer s disease

Transcription

1 Cmprehensive Research Plan: Cgnitive enhancers fr the treatment f Alzheimer s disease Pharmacepidemilgy Unit February 13 th, Bnd Street, Trnt ON, M5B 1W8 inf@dprn.ca

2 2 ODPRN Drug Class Review Prpsal: Pharmacepidemilgy Unit Study Title: Epidemilgic Analyses f Cgnitive Enhancers Objectives: 1. T examine natinal and prvincial trends in use f cgnitive enhancers acrss Canada 2. T perfrm crss prvincial cmparisns f the trends in cgnitive enhancer utilizatin 3. T describe characteristics f elderly patients prescribed publicallyfunded cgnitive enhancers in Ontari 4. T investigate the patterns f use f cgnitive enhancers amng elderly patients in Ontari 5. T summarize any bservatinal studies evaluating the cmparative safety and effectiveness f cgnitive enhancers Objective 1: Natinal and Prvincial Trends in Cgnitive Enhancers Drug Use Study Design: Study Ppulatin: Design: Time series analysis with quarterly time intervals Study perid: Natinal and prvincial trends (IMS Cmpuscript): January 2009 t September 2014 Ppulatin: All prvinces Data Surces: IMS Cmpuscript: aggregated data fr all prescriptins dispensed at retail pharmacies acrss Canada Inclusin Criteria: All privately and publically-funded cgnitive enhancer prescriptins dispensed in Canada: Dnepezil Galantamine Rivastigmine Memantine Outcme(s) f Interest: Measured ver entire study perid (quarterly): Number and rate f prescriptins dispensed Ttal cst f prescriptins Ttal number f units dispensed Stratify all analyses by: Prvince Payer (Public, Private, Cash) Cgnitive Enhancer Drug (Dnepezil, Galantamine, Rivastigmine, Memantine)

3 3 Limitatins: The IMS data is nly available at the prescriptin and unit level. Therefre, natinal and prvincial trends in prescribing cannt differentiate by indicatin. Objective 2: Crss-Prvincial Changes in Prescribing f Cgnitive Enhancers in Public Drug Prgrams Study Design: Study Ppulatin: Design: Time series analysis with quarterly time intervals Study perid: January 2000 t December 2013 Data Surce: Natinal Prescriptin Drug Utilizatin Infrmatin System Database (NPDUIS): aggregated data fr all publically funded prescriptins dispensed in Alberta, Saskatchewan, Manitba, New Brunswick, Nva Sctia, PEI and BC Ontari Drug Benefit Database (ODB): individual level data fr all publically funded prescriptins dispensed in Ontari. This dataset cntains additinal variables (lng-term care residence, public drug plan cverage) that is nt available thrugh NPDUIS Inclusin Criteria: All publically-funded cgnitive enhancer prescriptins dispensed in Alberta, Saskatchewan, Manitba, Ontari, New Brunswick, Nva Sctia, PEI and BC Elderly Patients (65 years f age and lder) Outcme(s) f Interest: Measured ver entire study perid (annually) Number and rate f users Number f prescriptins dispensed Ttal csts f cgnitive enhancers Average cst f cgnitive enhancers per user Stratify all analyses by: Prvince Age grups (65-69, 70-75, 75-80, 80+) Limitatins: Publically-funded, patient-level prescriptin data is nly available as f 2005 fr PEI and 2006 fr BC. We are therefre unable t determine cgnitive enhancers use prir t that date. There is n patient-level data available fr publically paid prescriptins in Quebec, Newfundland & Labradr r the Territries. Therefre, we will be unable t make cmparisns between Ontari rates and rates f use in these prvinces.

4 4 Objective 3: Characteristics f Elderly Patients Prescribed Cgnitive Enhancers in Ontari Study Design: Study Ppulatin: Design: Crss-sectinal analysis Study perid: January 2012 t December 2013 Data Surces: Ontari Drug Benefit Database (ODB) Canadian Institute fr Health Infrmatin-Discharge Abstract Database (CIHI-DAD) Natinal Ambulatry Care Reprting System Database (NACRS) Ontari Health Insurance Plan Claims Database (OHIP) ICES Physician Database (IPDB) Cntinuing Care Reprting Systems (fr Chrnic Care) (CCRS) Inclusin Criteria: All publically-funded beneficiaries ver the age f 65 in Ontari wh are prescribed a cgnitive enhancer Chrt Entry Date: defined as date f first prescriptin fr a cgnitive enhancer drug fllwing 65 th birthday, ver the study perid. Index Drug: Defined as the cgnitive enhancer drug that was prescribed n chrt entry date

5 5 Variables f Interest: Fr the established chrt, measure: Number f patients Number f new users New users aged 66 and lder defined as having n prescriptin fr a cgnitive enhancer in the past 365 days New users <66 years f age defined as having a prescriptin fr any drug in the past days and wh did nt have a prescriptin fr a cgnitive enhancer in the past 180 days Age at chrt entry date (mean, SD, and by categry (65-69, 70-75, 75-80, 80+)) Prprtin f patients wh were male Prprtin f patients residing in LTC at chrt entry Prprtin f urban residents at chrt entry Sciecnmic status (measured using incme quintiles at chrt entry) Average cst f cgnitive enhancer prescriptins per persn Prprtin f patients with diagnsed dementia within 5 years f index Defined by: 5-year lk back fr physician OHIP diagnsis cdes r CIHI-DAD admissin cdes related t dementia r use f cgnitive enhancers in year prir Cncmitant Psychtrpic use at index: Antipsychtics Antidepressants (SSRI, TCA, MAOI, ther) Benzdiazepines Md stabilizers Stimulants Prescriber f initial prescriptin: Specialist Psychiatrists Geriatricians Neurlgists General Practitiner Specialist visit in past 3 mnths prir t index (yes/n): Psychiatrists Geriatricians Neurlgists Number f hspitalizatin r ED visit within the last 1 year (median, IQR) Number f physician ffice visits within the last 1 year (median, IQR) Cmrbidities Charlsn cmrbidity scre (based n last 3 years f hspitalizatin data) Individual Cmpnents Number f medicatins used in past 1 year

6 6 Stratify analyses by: Cgnitive Enhancer drug (Dnepezil, Galantamine, Rivastigmine, Memantine) Limitatins: N infrmatin n medicatin use when hspitalized. Objective 4: Investigate the Adherence and Patterns f Use fr Newly initiated Cgnitive Enhancer Medicatins amng Elderly Patients in Ontari Study Design: Study Ppulatin: Design: Chrt Study Study perid: January 2009-December 2013 Accrual perid: January 2009-December 2012 Maximum fllw-up date: December 2013 (1 year minimum fllw-up) Data Surces: Ontari Drug Benefit Database (ODB) Canadian Institute fr Health Infrmatin-Discharge Abstract Database (CIHI-DAD) Natinal Ambulatry Care Reprting System Database (NACRS) Ontari Health Insurance Plan Claims Database (OHIP) ICES Physician Database (IPDB) Cntinuing Care Reprting Systems (fr Chrnic Care) (CCRS) Inclusin Criteria: All publically-funded beneficiaries ver the age f 66 in Ontari wh newly initiate a cgnitive enhancer ver the study perid (defined as n prescriptin fr a cgnitive enhancer in the past 365 days) Chrt Entry Date: defined as date f first prescriptin fr a cgnitive enhancer drug fllwing 66 th birthday, ver the study perid. Index Drug: Defined as the cgnitive enhancer drug that was prescribed n chrt entry date

7 7 Outcmes f interest: Duratin f Cgnitive Enhancer Therapy (defined in 2 ways): Relaxed Definitin Of Cntinued Cgnitive Enhancer Use Define nging use f cgnitive enhancer therapy accrding t receipt f a subsequent prescriptin within 180 days f the prir prescriptin. If n subsequent prescriptin, then persn discntinued use. Date f discntinuatin: date f last prescriptin + days supply f final prescriptin Strict Clinical Definitin f Cntinued Cgnitive Enhancer Use Define nging use f cgnitive enhancer therapy accrding t receipt f a subsequent prescriptin within 1.5 times the days supply f the prir prescriptin. If n subsequent prescriptin, then persn discntinued use. Date f discntinuatin: date f last prescriptin + days supply f final prescriptin. Fr each definitin reprt the fllwing: Ttal number f new users Number f cgnitive enhancer users with nly 1 prescriptin befre discntinuing Amng patients with mre than 1 prescriptin fr a cgnitive enhancer drug dispensed ver perid f cntinuus use reprt the fllwing: Age at chrt entry date (mean, SD, and by categry (66-69, 70-75, 75-80, 80+)) Prprtin f patients wh were male Prprtin f patients residing in LTC at chrt entry Amng patients residing in the cmmunity at chrt entry, reprt the prprtin wh enter int LTC within 1 year Prprtin f urban residents at chrt entry Sciecnmic status (measured using incme quintiles at chrt entry) Cmrbidities i. Charlsn cmrbidity scre (based n last 3 years f hspitalizatin data) Individual Cmpnents ii. Number f medicatins used in past year based n the drug name n prescriptin Prescriber f initial prescriptin: i. Specialist 1. Psychiatrists 2. Geriatricians 3. Neurlgists ii. General Practitiner Specialist visit in past 3 mnths prir t chrt entry (yes/n): i. Psychiatrists ii. Geriatricians iii. Neurlgists Prprtin with a diagnsis f dementia in last 3 years Number f hspitalizatin r ED visits within the last 1 year (median, IQR)

8 8 Number f physician ffice visits within the last 1 year (media, IQR) Outcmes f interest (cntinued): Over perid f nging use: Number f different cgnitive enhancer drugs prescribed ver fllw-up (Median (IQR), 1, 2, 3+) Prprtin f users wh are prescribed a different cgnitive enhancer drug within 6 mnths and 12 mnths f chrt entry Average cst f cgnitive enhancer prescriptins per persn Cncmitant psychtrpic medicatins prescribed: Antipsychtics Antidepressants (SSRI, TCA, MAOI, ther) Benzdiazepines Stimulants Md stabilizers Median duratin f cgnitive enhancer therapy Percent adherent t therapy at 1 year after chrt entry Analysis: Kaplan Meier curves cnstructed and lg-rank test used t test fr differences Stratified by LTC residence, age grup and sex Adjusted Cx Prprtinal Hazards Mdel Stratify abve analysis by: Cgnitive Enhancer drug (Dnepezil, Galantamine, Rivastigmine, Memantine) Limitatins Infrmatin is nt available fr medicatin use when hspitalized. Due t issues with incmplete data and unavailability f eligibility infrmatin, this analysis is restricted t patients aged 66 and lder. Therefre, these findings may nt be generalizable t the yunger ppulatin.