Estimation of Parkinson’s disease survival in Israeli men and women, using health maintenance organization pharmacy data in a unique approach

Abstract

The aim of this work was to estimate in an incident cohort of pharmacy-based PD patients the survival of men and women accounting for age at treatment initiation and to compare their gender-specific survival with that of the general Israeli population. A population-based cohort of 4,848 incident pharmacy-based PD cases with definite/probable/possible certainty was previously identified using a drug-tracer approach for 1999–2008. Survival analysis was performed for two time scales: survival after treatment initiation (disease duration), and life-time survival (life expectancy). Kaplan–Meier curves and Cox regressions were used to compare survival across gender. Gender-specific SMRs were calculated from national rates and were compared using Poisson regression. During the follow-up from first purchase of any anti-parkinsonian drug (mean 4.0 ± 2.6 years, range 2 months–10 years), 1,266 (26 %) of the cases died. Younger age at first anti-parkinsonian drug purchase and female gender were associated with increased survival after treatment initiation (HR = 1.089, 95 % CI 1.080–1.098 for 1-year age increase; HR = 0.716, 95 % CI 0.640–0.800, females vs. males). Life-time survival increased with older age at first anti-parkinsonian drug purchase and female gender (HR = 0.759, 95 % CI 0.746–0.771 for 1-year age increase; HR = 0.694, 95 % CI 0.621–0.776, females vs. males). Sensitivity analysis on a sub-cohort of definite cases (n = 2501) yielded similar results. In comparison to the general Israeli population, mortality among pharmacy-based PD patients was significantly increased (SMR_men = 1.69, 95 % CI 1.57–1.81, SMR_women = 1.49, 95 % CI 1.37–1.62), differently between genders (p < 0.01). Female gender was associated with longer, perhaps more benign disease course, and longer life expectancy. Earlier age at anti-parkinsonian drug initiation increased disease duration, but was associated with shorter life expectancy.

Appendix

See Tables 2, 3, 4, and 5.

Table 2 Algorithm for identifying PD cases and assigning them to certainty levels (definite, probable, possible) based on drug purchase data

Terms defined above (Table 2) are italicized in the algorithm table below

 

1	Minimum 1 purchase during the study period 1.1.1998–31.12.2008	No→	Exclusion
	Yes↓
2	20 ≤age at first purchase <85	No→	Exclusion
	Yes↓
3	Minimum 3 purchase months within FUP	No→	Exclusion
	Yes↓
4	Purchases of GR 3 only (bromocriptine) AND pattern suggesting indications other than PD, namely: subjects with first purchase in 2003 or later, or subjects with final purchase gap ≥365 days, or women with age at first purchase <50	Yes→	Exclusion
	No↓
5	FUP ≥3 years	No→	Go to step 15, algorithm for FUP < 3 years
	Yes↓
Algorithm for subjects with FUP ≥3 years
6	At least 1 observation segment with a minimum of 3 purchase months	No→	Exclusion
	Yes↓
7	At least 1 purchase month of GR 7 (apomorphine)	Yes→	Certainty level: definite
	No↓
	Note: As of step 8, all criteria are applied to the examined interval
8	During the examined interval, at least 24 purchase months of GR 1, 2, 4, or 5	Yes→	Certainty level: definite
	No↓
9	If age at first purchase <75: during at least 1 of the observation segments within the examined interval, minimum 9 purchase months of GR 1, 2, or 4; OR during any two of the observation segments within the examined interval, minimum 18 purchase months of GR 5 if age at first purchase ≥75: during at least 1 of the observation segments within the examined interval, minimum 9 purchase months of GR 1 or 2; OR during any two of the observation segments within the examined interval, minimum 18 purchase months of GR 4 or 5	Yes→	Certainty level: definite
	No↓
10	During at least 1 of the observation segments within the examined interval, minimum 6 simultaneous purchase months of drugs of two groups or more, any combination excluding (4 + 5)	Yes→	Certainty level: definite
	No↓
11	If age at first purchase <75: during at least one of the observation segments within the examined interval, minimum 6 purchase months of GR 1, 2, or 4, or 9 purchase months of GR 5; OR during any two of the observation segments within the examined interval, minimum 16 purchase months of GR 5 if age at first purchase ≥75: during at least one of the observation segments within the examined interval, minimum 6 purchase months of GR 1 or 2, or 9 purchase months of GR 4 or 5; OR during any two of the observation segments within the examined interval, minimum 16 purchase months of GR 4 or 5	Yes→	Go to step 13
	No↓
12	During at least one of the observation segments within the examined interval, minimum 6 simultaneous purchase months of drugs of GR (4 + 5), OR minimum 3 simultaneous purchase months of drugs of two groups or more, any combination excluding (4 + 5)	No→	Go to step 14
	Yes↓
13	Final purchase gap <365 days	Yes→	Certainty level: probable
	No↓
14	Remaining subjects	Yes→	Certainty level: possible
	End
Algorithm for subjects with FUP <3 years
15	Age at first purchase ≤65; OR lag to first purchase ≥1 year and deceased during the study period	Yes→	Go to step 6
	No↓
16	At least 1 observation segment with a minimum of 3 purchase months, OR during any two observation segments within the examined interval, minimum 4 purchase months, OR—for subjects with FUP <2 years—minimum 3 purchase months within the entire FUP	No→	Exclusion
	Yes↓
17	Lag to first purchase <1 year and deceased during the study period	Yes→	Go to step 7
	No↓
18	At least 1 purchase month of GR 7 (apomorphine)	Yes→	Certainty level: definite
	No↓
19	During the examined interval, at least 24 purchase months of GR 1, 2, 4, or 5	Yes→	Certainty level: definite
	No↓
20	During at least one of the observation segments within the examined interval, minimum 6 purchase months of GR 1, 2, or 4; OR during any two of the observation segments within the examined interval, minimum 18 purchase months of GR 5	Yes→	Certainty level: definite
	No↓
21	During at least 1 of the observation segments within the examined interval, minimum 6 simultaneous purchase months of drugs of two groups or more, any combination excluding (4 + 5), OR minimum 3 simultaneous purchase months of drugs of two groups or more, any combination of GR 1, 2, 4, 6	Yes→	Certainty level: definite
	No↓
22	During at least 1 of the observation segments within the examined interval, minimum 9 purchase months of GR 5; OR during any two of the observation segments within the examined interval, minimum 16 purchase months of GR 5	Yes→	Certainty level: probable
	No↓
23	During at least 1 of the observation segments within the examined interval, minimum 6 simultaneous purchase months of drugs of GR (4 + 5), OR minimum 3 simultaneous purchase months of drugs of two groups or more, any combination excluding (4 + 5)	Yes→	Certainty level: probable
	No↓
24	Final purchase gap <365 days	No→	Go to step 26
	Yes↓
25	At least 1 observation segment with a minimum of 3 purchase months of GR 1, 2, or 4 OR during any two observation segments within the examined interval, minimum 4 purchase months and no purchases of GR 3 or 5, OR—for subjects with FUP <2 years—minimum 3 purchase months within the entire FUP and no purchases of GR 3 or 5	Yes→	Certainty level: probable
	No↓
26	Remaining subjects	Yes→	Certainty level: possible
	End

Table 3 Characteristics of the incident PD cohort; comparison between men and women

Table 4 Sensitivity analysis

Table 5 Mortality among incident PD cases compared to the general Israeli population

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