Drug Utilization Studies in Pregnant Women for Newly Licensed Medicinal Products: A Contribution from IMI ConcePTION

Table 4

Considerations for study methods and results.

Description of source population (population where the data are obtained)	Name of database, region/country, healthcare system; Total number of people in the database, timeframe. Ideally, also the proportion of mother/infant dyads linkable in the database, capture and linkage of outpatient and inpatient prescribing and dispensing	9
Period (dates)	Study period, years included	10
Exposure to the new medicine(s)	Medicine code lists (e.g., ATC, Read, and/or NDC codes); Exposure definition (e.g., reference half-life used to calculate exposure for preconception administration); Exposure duration	9
Exposure to the medicine(s) that could be used as potential comparators	Exposure definition (e.g., reference half-life used to calculate exposure for preconception administration); Exposure duration, coprescription for a similar indication	3
Medicine details	Prescription, reimbursement, dispensing records, medication administration/actual use, duration of treatment, dosage, etc.; Formulation; Route of administration; Comedications	9
Indication for prescription	State how the indication for the medicines studied will be ascertained and why documentation may be incomplete; Indicate whether “diagnosis ever” will be applied and time of records; Validity of data on indication for prescription. If algorithms are used to establish indication, these should have high specificity and sensitivity, as determined by internal exploration or the available literature	10
Description of pregnancy	Use of birth registers and/or algorithms to identify pregnancies within the database, including multiple pregnancies; Best estimates of start and end dates of a pregnancy and how these are obtained. Use of sensitivity analyses where not all pregnancies have ultrasound dating	6
Description of stratifications	Trimesters with definitions; Trimester 1: from (1^st day) last menstrual period (LMP) to after LMP; or end of pregnancy, whichever earlier; (i) Trimester 2: from day 98 after (1^st day) LMP to after LMP; or end of pregnancy, whichever earlier; (ii) Trimester 3: from day 196 after (1^st day) LMP onwards until end of pregnancy; Defining by weeks and days accounts for potential differences in databases	1
Statistical analyses	Descriptive analyses: (i) General characteristics (counts and percentages) (above); (ii) Number of pregnant women in the data source (some may have >1 pregnancy); (iii) Number of pregnancies/births during study period; (iv) Number of pregnancies/births that can be linked to infants; (v) Number of pregnancies ending in pregnancy loss; (vi) Number/proportion of pregnancies exposed to the study medicine; (vii) Number/proportion prescribed the medicine more than once; (viii) Number/proportion of pregnancies exposed to comparator medicine(s); (ix) Proportion of women of childbearing age with medicated and unmedicated condition under consideration; (x) Proportion of women with new medicine and comparator medicines during pregnancy; (xi) Proportion of women without documented indication of new medicine and comparator medicines during pregnancy; (xii) Proportion of pregnant women prescribed new medicine and comparator medicines; (xiii) Proportion of women of childbearing age prescribed new medicine (numerator: users of medicine, denominator: women of childbearing age); Inferential analyses adjusted for covariates listed below. Time-varying covariates may be used, if appropriate; Time-trend analyses; Interrupted time series, e.g., to consider regulatory interventions; Meta-analyses of several databases	11
Methods to address bias	Describe: missing data, potential for misclassification bias, and unmeasured confounding	8
Description of women in the database (this list is not exhaustive)	General descriptive characteristics: (i) Maternal ages (if accurately available); (ii) Maternal socioeconomic status; (iii) Marital status, if not colinear with socioeconomic status; (iv) Substance misuse, smoking, heavy alcohol use; Pregnancy-related conditions (by trimester): (i) Maternal BMI; (ii) Gestational diabetes; (iii) Gestational hypertension; (iv) Preeclampsia; (v) Infections and fevers in pregnancy; (vi) All medicine used during pregnancy; Comorbidities before pregnancy; Coprescriptions during pregnancy	5
Length of follow-up in database?	Years of follow-up available	9

No studies reported on data linkage between datasets.