Evaluating a Structured Reporting Template to Increase Transparency and Reduce Review Time for Healthcare Database Studies

OMB Control No. 0910-0497 Expiration date: 10/31/2020

Appendix B1: Structured Reporting Template (word version)

TABLE OF CONTENTS

Administrative Information

Version History

Design Diagram

Attrition Table

Power Calculation

Analysis Specification

Glossary of Terminology

 

APPENDICES (with details of algorithms)

A - Study Population Entry Criteria (Exposure)

B - Drug, Diagnosis, and Procedure-Based Inclusion/Exclusion Criteria

C - Drug, Diagnosis, and Procedure-Based Covariates

D - Outcome

E - Care Setting

VERSION HISTORY

Version Date	Version Number	Change Log	Rationale for Change
November 12, 2018	v2	Added covariate: "co-prescription of Drug C" measured in days [-183, 0] in any care setting and diagnosis position	Added because of concern that Drug C may interact with effect of Drug A and B
April 15, 2019	v3	Changed covariate assessment window from days [-183, -1] to [-183, 0]	Changed assessment window to include day 0, due to concern that important diagnoses occurring on the day of drug dispensation may be missed

ATTRITION TABLE
	Less Excluded Patients	Remaining Patients
All patients
Did not meet cohort entry criteria (dispensation of drug A or drug B)
Excluded due to insufficient prior enrollment (<183 days with 45-day gaps allowed)
Excluded due to prior use of referent (Drug B)
Excluded due to prior use of exposure (Drug A)
Excluded because patient qualified in >1 exposure category
Excluded based on Age <18
Excluded based on Age ≥65
Excluded based on Gender (unknown)
Excluded based on Drug supply <=0 days
Excluded based on Drug A (additional formulations and combinations not included in exposure)
Excluded based on Drug B (additional formulations and combinations not included in referent)
Excluded based on absence of community acquired pneumonia diagnosis within 14 days prior to index date
Excluded based on absence of chest x-ray within 14 days prior to index date
Excluded based on inpatient admission within 90 days prior to index date
Excluded if censored on day 1
Final cohort
	Drug A initiators N =
	Drug B initiators N =

ANALYSIS SPECIFICATIONS
Analyses
	Primary	Secondary 1	Secondary 2	Subgroup	Sensitivity
Outcome:	Myocardial infarction	Stroke	TIA	n/a	Myocardial infarction
Software:	SAS 9.4: PHREG, PROC LOGISTIC, Pharmacoepi Toolbox nearest neighbor matching macro (http://www.drugepi.org/dope-downloads/)	SAS 9.4: PHREG, PROC LOGISTIC, Pharmacoepi Toolbox nearest neighbor matching macro (http://www.drugepi.org/dope-downloads/)	SAS 9.4: PHREG, PROC LOGISTIC, Pharmacoepi Toolbox nearest neighbor matching macro (http://www.drugepi.org/dope-downloads/)		SAS 9.4: PHREG, PROC LOGISTIC, Pharmacoepi Toolbox nearest neighbor matching macro (http://www.drugepi.org/dope-downloads/)
Model(s):	Outcome: Cox proportional hazards model, Propensity score: logistic regression	Outcome: Cox proportional hazards model, Propensity score: logistic regression	Outcome: Cox proportional hazards model, Propensity score: logistic regression		Outcome: Cox proportional hazards model, Propensity score: logistic regression
Confounding Adjustment (check all that apply and provide details, where requested)
Bivariate
Multivariable
Propensity Score Matching	X	X	X
(specify matching algorithm, ratio, and caliper)	Nearest neighbor, Ratio = fixed 1:1, Caliper = 0.025	Nearest neighbor, Ratio = fixed 1:1, Caliper = 0.025	Nearest neighbor, Ratio = fixed 1:1, Caliper = 0.025
Propensity Score Weighting					X
Confounding Adjustment (check all that apply and provide details, where requested)
(specify weight formula, trimming, truncation decisions)					Exposed weight = 1, Comparator weight = PS/(1-PS), 1% asymmetrical trim
Propensity Score Stratification
(specify strata definition)
Other
(specify details)
Missing Data Methods (check all that apply)
Missing Indicators
Complete Case
Last Value Carried Forward
Multiple Imputation
Other (please specify)…

GLOSSARY
Term	Definition
Confounder	Variable other than the exposure of interest or outcome under investigation that is: 1) associated with exposure; 2) a risk factor for the outcome; and 3) not on the causal pathway between the exposure and the outcome. A confounder can artificially inflate or reduce the magnitude of association between an exposure and outcome.
Covariates	Variables that are neither exposure nor outcome of interest but are measured to describe a population or because they may be a confounder to account for in analyses.
Data Extraction Date	The date when the data were extracted from the dynamic healthcare database.
Days Supplied	Number of days supplied for a dispensed prescription.
Eligible Cohort Entry Period	Calendar time frame, during which cohort entry dates are identified.
Empirically-Defined Covariates	Covariates that are not prespecified by the investigator. The selection of these covariates is based on applying algorithms to the data. The algorithms for covariate selection may be tuned by investigator-specified parameters.
Enrollment/Coverage	For insurance claims data, this may refer to periods of enrollment in medical and/or drug plans. For electronic health record databases, this may refer to algorithms designed to identify patients whose healthcare contacts are likely to be covered within the healthcare system.
Enrollment Gap	Maximum number of days allowed between two consecutive enrollment periods to still be considered “continuously enrolled.”
Follow-Up Window	The interval during which occurrence of the outcome of interest in the study population will be included in the analysis.
Grace Window	Number of days added to days’ supply to allow for non-adherence or account for the hypothesized biologic exposure risk window. Operationally, this could be defined as the number of extra days added to the end of a days’ supply to extend time counted as "exposed." This grace may bridge the gap between dispensations, where the days’ supply dispensed does not cover all days until the refill.
Index Date	The date when subjects enter the study population (cohort entry date, outcome event date). It is defined based on events in the patient's longitudinal timeline; other windows are defined relative to the index date.
Assessment Window	Interval during which a patient is required to have evidence of a pre-existing condition (diagnosis/procedure/drug dispensing). May be used for washout of exposure or outcome, exclusion assessment, or covariate assessment.
Predefined Covariates	Covariates that are prespecified and defined by the investigator in the protocol.
Principal Diagnosis	Diagnosis or condition established to be chiefly responsible for admission of the patient to the hospital.
Source Data Range	The calendar time range covered by a data source that is available.
Stockpiling Algorithm	Algorithm defining how early refills are handled when determining length of exposure follow up.
Study Period	Calendar time interval of data available for study, including pre-index date assessment windows and post-index follow up.
Treatment Episode	Continuous period of exposure, defined by using dispensation date + days’ supply and applying stockpiling algorithms and/or grace windows.
Washout Window	Minimum number of days a patient is required to have no evidence of prior exposure and/or outcome.
Wildcard	Symbol used to represent any single alphanumeric digit in code algorithms. For example, 410.*1, where * is the wildcard.

Appendix A: Study Population Entry Criteria

Study Entry Criterion	NDC	Generic Name	Brand Name	Route	Strength
Drug A	00003016050	drug A	Awesome Drug	tablet	250mg
Drug B	00003016050	drug B	Really Cool Drug	tablet	250mg



Appendix B: Drug, Diagnosis, and Procedure-Based Inclusion/Exclusion Criteria

Exclusion Criteria	Code	Code Category	Code Type	Description	Route	Strength
Drug A	00003016050	drug A	NDC	Awesome Drug	tablet	250mg
Drug B	00003016050	drug B	NDC	Really Cool Drug	tablet	250mg
Drug A	01003016050	drug A	NDC	Awesome Drug oral	oral suspension	5 ml
Drug B	00803016050	drug B	NDC	Really Cool Drug injectable	injectable	5 y injectable
Chest radiography	87.44	PX	09	Routine chest x-ray, so described
Chest radiography	87.49	PX	09	Other chest x-ray
Chest radiography	71010	PX	C4	Radiologic examination, chest; single view, frontal
Chest radiography	71015	PX	C4	Radiologic examination, chest; stereo, frontal
Chest radiography	71020	PX	C4	Radiologic examination, chest, 2 views, frontal and lateral / Radiologic examination, chest, 2 views, frontal and lateral; / Radiologic examination, chest, two views, frontal and lateral
Chest radiography	71021	PX	C4	Radiologic examination, chest, 2 views, frontal and lateral; with apical lordotic procedure / Radiologic examination, chest, two views, frontal and lateral; with apical lordotic procedure
Chest radiography	71022	PX	C4	Radiologic examination, chest, 2 views, frontal and lateral; with oblique projections / Radiologic examination, chest, two views, frontal and lateral; with oblique projections
Chest radiography	71023	PX	C4	Radiologic examination, chest, 2 views, frontal and lateral; with fluoroscopy / Radiologic examination, chest, two views, frontal and lateral; with fluoroscopy
Chest radiography	71030	PX	C4	Radiologic examination, chest, complete, minimum of 4 views / Radiologic examination, chest, complete, minimum of 4 views; / Radiologic examination, chest, complete, minimum of four views
Chest radiography	71034	PX	C4	Radiologic examination, chest, complete, minimum of 4 views; with fluoroscopy / Radiologic examination, chest, complete, minimum of four views; with fluoroscopy
Chest radiography	71035	PX	C4	Radiologic examination, chest, special views (e.g., lateral decubitus, Bucky studies)
Community-acquired pneumonia	480	DX	09	VIRAL PNEUMONIA
Community-acquired pneumonia	480.0	DX	09	PNEUMONIA DUE TO ADENOVIRUS
Community-acquired pneumonia	480.1	DX	09	PNEUMONIA DUE TO RESPIRATORY SYNCYTIAL VIRUS
Community-acquired pneumonia	480.2	DX	09	PNEUMONIA DUE TO PARAINFLUENZA VIRUS
Community-acquired pneumonia	480.3	DX	09	PNEUMONIA DUE TO SARS-ASSOCIATED CORONAVIRUS
Community-acquired pneumonia	480.8	DX	09	PNEUMONIA DUE TO OTHER VIRUS NOT ELSEWHERE CLASSIFIED
Community-acquired pneumonia	480.9	DX	09	VIRAL PNEUMONIA UNSPECIFIED
Community-acquired pneumonia	481	DX	09	PNEUMOCOCCAL PNEUMONIA [STREPTOCOCCUS PNEUMONIAE PNEUMONIA]
Community-acquired pneumonia	482	DX	09	OTHER BACTERIAL PNEUMONIA
Community-acquired pneumonia	482.0	DX	09	PNEUMONIA DUE TO KLEBSIELLA PNEUMONIAE
Community-acquired pneumonia	482.1	DX	09	PNEUMONIA DUE TO PSEUDOMONAS
Community-acquired pneumonia	482.2	DX	09	PNEUMONIA DUE TO HEMOPHILUS INFLUENZAE (H. INFLUENZAE)
Community-acquired pneumonia	482.3	DX	09	PNEUMONIA DUE TO STREPTOCOCCUS
Community-acquired pneumonia	482.30	DX	09	PNEUMONIA DUE TO STREPTOCOCCUS UNSPECIFIED
Community-acquired pneumonia	482.31	DX	09	PNEUMONIA DUE TO STREPTOCOCCUS GROUP A
Community-acquired pneumonia	482.32	DX	09	PNEUMONIA DUE TO STREPTOCOCCUS GROUP B
Community-acquired pneumonia	482.39	DX	09	PNEUMONIA DUE TO OTHER STREPTOCOCCUS
Community-acquired pneumonia	482.4	DX	09	PNEUMONIA DUE TO STAPHYLOCOCCUS
Community-acquired pneumonia	482.40	DX	09	PNEUMONIA DUE TO STAPHYLOCOCCUS UNSPECIFIED
Community-acquired pneumonia	482.41	DX	09	METHICILLIN SUSCEPTIBLE PNEUMONIA DUE TO STAPHYLOCOCCUS AUREUS
Community-acquired pneumonia	482.42	DX	09	METHICILLIN RESISTANT PNEUMONIA DUE TO STAPHYLOCOCCUS AUREUS
Community-acquired pneumonia	482.49	DX	09	OTHER STAPHYLOCOCCUS PNEUMONIA
Community-acquired pneumonia	482.8	DX	09	PNEUMONIA DUE TO OTHER SPECIFIED BACTERIA
Community-acquired pneumonia	482.81	DX	09	PNEUMONIA DUE TO ANAEROBES
Community-acquired pneumonia	482.82	DX	09	PNEUMONIA DUE TO ESCHERICHIA COLI [E.COLI]
Community-acquired pneumonia	482.83	DX	09	PNEUMONIA DUE TO OTHER GRAM-NEGATIVE BACTERIA
Community-acquired pneumonia	482.84	DX	09	PNEUMONIA DUE TO LEGIONNAIRES' DISEASE
Community-acquired pneumonia	482.89	DX	09	PNEUMONIA DUE TO OTHER SPECIFIED BACTERIA
Community-acquired pneumonia	482.9	DX	09	BACTERIAL PNEUMONIA UNSPECIFIED
Community-acquired pneumonia	483	DX	09	PNEUMONIA DUE TO OTHER SPECIFIED ORGANISM
Community-acquired pneumonia	483.0	DX	09	PNEUMONIA DUE TO MYCOPLASMA PNEUMONIAE
Community-acquired pneumonia	483.1	DX	09	PNEUMONIA DUE TO CHLAMYDIA
Community-acquired pneumonia	483.8	DX	09	PNEUMONIA DUE TO OTHER SPECIFIED ORGANISM
Community-acquired pneumonia	484	DX	09	PNEUMONIA IN INFECTIOUS DISEASES CLASSIFIED ELSEWHERE
Community-acquired pneumonia	484.1	DX	09	PNEUMONIA IN CYTOMEGALIC INCLUSION DISEASE
Community-acquired pneumonia	484.3	DX	09	PNEUMONIA IN WHOOPING COUGH
Community-acquired pneumonia	484.5	DX	09	PNEUMONIA IN ANTHRAX
Community-acquired pneumonia	484.6	DX	09	PNEUMONIA IN ASPERGILLOSIS
Community-acquired pneumonia	484.7	DX	09	PNEUMONIA IN OTHER SYSTEMIC MYCOSES
Community-acquired pneumonia	484.8	DX	09	PNEUMONIA IN OTHER INFECTIOUS DISEASES CLASSIFIED ELSEWHERE
Community-acquired pneumonia	485	DX	09	BRONCHOPNEUMONIA ORGANISM UNSPECIFIED
Community-acquired pneumonia	486	DX	09	PNEUMONIA ORGANISM UNSPECIFIED
Community-acquired pneumonia	487	DX	09	INFLUENZA
Community-acquired pneumonia	487.0	DX	09	INFLUENZA WITH PNEUMONIA
Community-acquired pneumonia	487.1	DX	09	INFLUENZA WITH OTHER RESPIRATORY MANIFESTATIONS
Community-acquired pneumonia	487.8	DX	09	INFLUENZA WITH OTHER MANIFESTATIONS
Community-acquired pneumonia	038.0	DX	09	STREPTOCOCCAL SEPTICEMIA
Community-acquired pneumonia	038.2	DX	09	PNEUMOCOCCAL SEPTICEMIA
Community-acquired pneumonia	041.0	DX	09	STREPTOCOCCUS INFECTION IN CONDITIONS CLASSIFIED ELSEWHERE AND OF UNSPECIFIED SITE
Community-acquired pneumonia	041.00	DX	09	STREPTOCOCCUS INFECTION IN CONDITIONS CLASSIFIED ELSEWHERE AND OF UNSPECIFIED SITE STREPTOCOCCUS UNSPECIFIED
Community-acquired pneumonia	041.01	DX	09	STREPTOCOCCUS INFECTION IN CONDITIONS CLASSIFIED ELSEWHERE AND OF UNSPECIFIED SITE STREPTOCOCCUS GROUP A
Community-acquired pneumonia	041.02	DX	09	STREPTOCOCCUS INFECTION IN CONDITIONS CLASSIFIED ELSEWHERE AND OF UNSPECIFIED SITE STREPTOCOCCUS GROUP B
Community-acquired pneumonia	041.03	DX	09	STREPTOCOCCUS INFECTION IN CONDITIONS CLASSIFIED ELSEWHERE AND OF UNSPECIFIED SITE STREPTOCOCCUS GROUP C
Community-acquired pneumonia	041.04	DX	09	STREPTOCOCCUS INFECTION IN CONDITIONS CLASSIFIED ELSEWHERE AND OF UNSPECIFIED SITE STREPTOCOCCUS GROUP D [ENTEROCOCCUS]
Community-acquired pneumonia	041.05	DX	09	STREPTOCOCCUS INFECTION IN CONDITIONS CLASSIFIED ELSEWHERE AND OF UNSPECIFIED SITE STREPTOCOCCUS GROUP G
Community-acquired pneumonia	041.09	DX	09	STREPTOCOCCUS INFECTION IN CONDITIONS CLASSIFIED ELSEWHERE AND OF UNSPECIFIED SITE OTHER STREPTOCOCCUS
Community-acquired pneumonia	041.2	DX	09	PNEUMOCOCCUS INFECTION IN CONDITIONS CLASSIFIED ELSEWHERE AND OF UNSPECIFIED SITE
Community-acquired pneumonia	320.1	DX	09	PNEUMOCOCCAL MENINGITIS

Appendix C: Drug, Diagnosis, and Procedures, Based on Covariates

(Note: as the file is extensive, we provide the first few covariates, here, only; for the full list, please visit the excel document).

Covariate	Code	Code Category	Code Type	Description	Strength	Dose
Degenerative disease of central nervous system	330	DX	09	CEREBRAL DEGENERATIONS USUALLY MANIFEST IN CHILDHOOD
Degenerative disease of central nervous system	330.0	DX	09	LEUKODYSTROPHY
Degenerative disease of central nervous system	330.1	DX	09	CEREBRAL LIPIDOSES
Degenerative disease of central nervous system	330.2	DX	09	CEREBRAL DEGENERATION IN GENERALIZED LIPIDOSES
Degenerative disease of central nervous system	330.3	DX	09	CEREBRAL DEGENERATION OF CHILDHOOD IN OTHER DISEASES CLASSIFIED ELSEWHERE
Degenerative disease of central nervous system	330.8	DX	09	OTHER SPECIFIED CEREBRAL DEGENERATIONS IN CHILDHOOD
Degenerative disease of central nervous system	330.9	DX	09	UNSPECIFIED CEREBRAL DEGENERATION IN CHILDHOOD
Degenerative disease of central nervous system	331	DX	09	OTHER CEREBRAL DEGENERATIONS
Degenerative disease of central nervous system	331.0	DX	09	ALZHEIMER'S DISEASE
Degenerative disease of central nervous system	331.1	DX	09	FRONTOTEMPORAL DEMENTIA
Degenerative disease of central nervous system	331.11	DX	09	PICK'S DISEASE
Degenerative disease of central nervous system	331.19	DX	09	OTHER FRONTOTEMPORAL DEMENTIA
Degenerative disease of central nervous system	331.2	DX	09	SENILE DEGENERATION OF BRAIN
Degenerative disease of central nervous system	331.3	DX	09	COMMUNICATING HYDROCEPHALUS
Degenerative disease of central nervous system	331.4	DX	09	OBSTRUCTIVE HYDROCEPHALUS
Degenerative disease of central nervous system	331.5	DX	09	IDIOPATHIC NORMAL PRESSURE HYDROCEPHALUS (INPH)
Degenerative disease of central nervous system	331.6	DX	09	CORTICOBASAL DEGENERATION
Degenerative disease of central nervous system	331.7	DX	09	CEREBRAL DEGENERATION IN DISEASES CLASSIFIED ELSEWHERE
Degenerative disease of central nervous system	331.8	DX	09	OTHER CEREBRAL DEGENERATION
Degenerative disease of central nervous system	331.81	DX	09	REYE'S SYNDROME
Degenerative disease of central nervous system	331.82	DX	09	DEMENTIA WITH LEWY BODIES
Degenerative disease of central nervous system	331.83	DX	09	MILD COGNITIVE IMPAIRMENT SO STATED
Degenerative disease of central nervous system	331.89	DX	09	OTHER CEREBRAL DEGENERATION
Degenerative disease of central nervous system	331.9	DX	09	CEREBRAL DEGENERATION UNSPECIFIED
Degenerative disease of central nervous system	332	DX	09	PARKINSON'S DISEASE
Degenerative disease of central nervous system	332.0	DX	09	PARALYSIS AGITANS
Degenerative disease of central nervous system	332.1	DX	09	SECONDARY PARKINSONISM
Degenerative disease of central nervous system	333	DX	09	OTHER EXTRAPYRAMIDAL DISEASE AND ABNORMAL MOVEMENT DISORDERS
Degenerative disease of central nervous system	333.0	DX	09	OTHER DEGENERATIVE DISEASES OF THE BASAL GANGLIA
Degenerative disease of central nervous system	333.1	DX	09	ESSENTIAL AND OTHER SPECIFIED FORMS OF TREMOR
Degenerative disease of central nervous system	333.2	DX	09	MYOCLONUS
Degenerative disease of central nervous system	333.3	DX	09	TICS OF ORGANIC ORIGIN
Degenerative disease of central nervous system	333.4	DX	09	HUNTINGTON'S CHOREA
Degenerative disease of central nervous system	333.5	DX	09	OTHER CHOREAS
Degenerative disease of central nervous system	333.6	DX	09	GENETIC TORSION DYSTONIA
Degenerative disease of central nervous system	333.7	DX	09	ACQUIRED TORSION DYSTONIA
Degenerative disease of central nervous system	333.71	DX	09	ATHETOID CEREBRAL PALSY
Degenerative disease of central nervous system	333.72	DX	09	ACUTE DYSTONIA DUE TO DRUGS
Degenerative disease of central nervous system	333.79	DX	09	OTHER ACQUIRED TORSION DYSTONIA
Degenerative disease of central nervous system	333.8	DX	09	FRAGMENTS OF TORSION DYSTONIA
Degenerative disease of central nervous system	333.81	DX	09	BLEPHAROSPASM
Degenerative disease of central nervous system	333.82	DX	09	OROFACIAL DYSKINESIA
Degenerative disease of central nervous system	333.83	DX	09	SPASMODIC TORTICOLLIS



Appendix D: Outcome

Outcome	Code	Code Category	Code Type	Description
Myocardial Infarction	41001	DX	ICD9	Acute myocardial infarction of anterolateral wall, initial episode of care

Appendix E: Care Setting

CARE SETTING
IP = inpatient	All claims in the MarketScan inpatient admissions table and inpatient services are coded as IP; primary diagnosis is defined by the inpatient admissions primary diagnosis, only.
ED = emergency department	Any encounters in the inpatient service or outpatient service table with SVCSCAT ending in '20' or STDPLAC in ('23', '41', 42').
AV = ambulatory visit	Based on outpatient service table values for STDPLAC (see below).
IS = institutional stay	Based on outpatient service table values for STDPLAC (see below).
OA = other ambulatory visit	Based on outpatient service table values for STDPLAC (see below).
STDPLAC
Value	Label	Care Setting
1	Pharmacy	AV
3	School	AV
4	Homeless Shelter	AV
11	Office	AV
12	Patient Home	AV
13	Assisted Living Facility	IS
14	Group Home	IS
15	Mobile Unit	AV
16	Temporary Lodging	AV
17	Walk-In Retail Health Clinic	AV
18	Place of Employment - Worksite	AV
20	Urgent Care Facility	AV
21	Inpatient Hospital	AV
22	Outpatient Hospital	AV
23	Emergency Room - Hospital	ED
24	Ambulatory Surgical Center	AV
25	Birthing Center	AV
26	Military Treatment Facility	AV
Value	Label	Care Setting
27	Inpatient Long-Term Care (NEC)	IS
28	Other Inpatient Care (NEC)	IS
31	Skilled Nursing Facility	IS
32	Nursing Facility	IS
33	Custodial Care Facility	IS
34	Hospice	IS
35	Adult Living Care Facility	IS
41	Ambulance (land)	ED
42	Ambulance (air or water)	ED
49	Independent Clinic	AV
50	Federally Qualified Health Center	AV
51	Inpatient Psychiatric Facility	AV
52	Psych Facility Partial Hospital	AV
53	Community Mental Health Center	AV
54	Intermed Care/Mental Retarded	AV
55	Residential Substance Abuse Facility	AV
56	Psych Residential Treatment Center	AV
57	Non-Resident Substance Abuse Facility	AV
60	Mass Immunization Center	AV
61	Comprehensive Inpatient Rehab Facility	AV
62	Comprehensive Outpatient Rehab Facility	AV
65	End-Stage Renal Disease Facility	AV
71	State/Local Public Health Clinic	AV
72	Rural Health Clinic	AV
81	Independent Laboratory	AV
95	Outpatient (NEC)	AV
98	Pharmacy	AV
99	Other Unlisted Facility	OA

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