HARPER
  • Home
  • Protocol

On this page

  • 1 Title page
  • 2 Abstract
  • 3 Amendments and updates
  • 4 Milestones
  • 5 Rationale and background
  • 6 Research question and objectives
  • 7 Research methods
    • 7.1 Study design
    • 7.2 Study design diagram3,4
    • 7.3 Setting
      • 7.3.1 Context and rationale for definition of time 0 (and other primary time anchors) for entry to the study population
      • 7.3.2 Context and rationale for study inclusion criteria
      • 7.3.3 Context and rationale for study exclusion criteria
    • 7.4 Variables
      • 7.4.1 Context and rationale for exposure(s) of interest
      • 7.4.2 Context and rationale for outcome(s) of interest
      • 7.4.3 Context and rationale for follow up
      • 7.4.4 Context and rationale for covariates (confounding variables and effect modifiers, e.g. risk factors, comorbidities, comedications)
    • 7.5 Data analysis
      • 7.5.1 Context and rationale for analysis plan
    • 7.6 Data sources
      • 7.6.1 Context and rationale for data sources
    • 7.7 Data management
    • 7.8 Quality control
    • 7.9 Study size and feasibility
  • 8 Limitation of the methods
  • 9 Protection of human subjects
  • 10 Reporting of adverse events
  • 11 References
  • 12 Appendices
  • 13 Session info
    • 13.1 Loaded packages
    • 13.2 Session info
    • 13.3 Repositories
  • 14 Change log

Study protocol

Based on the HARPER template

Author
Affiliation

FIRST, LAST

AFFILIATION NAME

Published

July 3, 2023

1 Title page

This protocol is based on the HARmonized Protocol Template to Enhance Reproducibility (HARPER) of Hypothesis Evaluating Real-World Evidence Studies on Treatment Effects: A Good Practices Report of a Joint ISPE/ISPOR Task Force (HARPER) protocol by Wang SV et al.1,2

Title

Research question and objectives

Protocol version

Contributors

Primary investigator contact information:

Contributor names:

Study registration

Site:

Identifier:

Sponsor

Organization:

Contact:

Conflict of interest

2 Abstract

3 Amendments and updates

Amendments and updates

Version date Version number Section of protocol Amendment or update Reason
<Date of the protocol version change> <Number or other identifier for the protocol version> <Brief text description of which sections of the protocol were amended> <Brief text description of what changes were involved with the protocol amendment> <Brief text description of the rationale for the protocol amendment>

4 Milestones

Table 1:

Milestones

Milestone Date
<Milestone description> <Date>
<Milestone description> <Date>
<Milestone description> <Date>

5 Rationale and background

What is known about the condition:

What is known about the exposure of interest:

Gaps in knowledge:

What is the expected contribution of this study?

The purpose of this protocol is to describe the emulation of trial INSERT TRIAL NAME. The primary trial estimate targeted for emulation is INSERT. Market availability of EXPOSURE began DATE.

6 Research question and objectives

Table 2: Research questions and objectives

(a)

A. Primary research question and objective

Study element Specification
Objective: <Text>
Hypothesis: <Text>
Population (mention key inclusion-exclusion criteria): <Text>
Exposure: <Text>
Comparator: <Text>
Outcome: <Text>
Time (when follow up begins and ends): <Text>
Setting: <Text>
Main measure of effect: <Text>
(b)

B. Secondary research question and objective

Study element Specification
Objective: <Text>
Hypothesis: <Text>
Population (mention key inclusion-exclusion criteria): <Text>
Exposure: <Text>
Comparator: <Text>
Outcome: <Text>
Time (when follow up begins and ends): <Text>
Setting: <Text>
Main measure of effect: <Text>

7 Research methods

7.1 Study design

Research design (e.g. cohort, case-control, etc.):

Rationale for study design choice:

7.2 Study design diagram3,4

7.3 Setting

7.3.1 Context and rationale for definition of time 0 (and other primary time anchors) for entry to the study population

Table 3:

Operational Definition of Time 0 (index date) and other primary time anchors.

Study population name(s) Time Anchor Description (e.g. time 0) Number of entries Type of entry Washout window Care setting Code type Diagnosis position Incident with respect to… Measurement characteristics/ validation Source of algorithm
<Text> <Text> <Text> <Text> <Text> <Text> <Text> <Text> <Text> <Text> <Text>

7.3.2 Context and rationale for study inclusion criteria

Table 4:

Operational Definitions of Inclusion Criteria

Criterion Details Order of application Assessment window Care settings Code Type Diagnosis position Applied to study populations: Measurement characteristics/ validation Source of algorithm
<Text> <Text> <Text> <Text> <Text> <Text> <Text> <Text> <Text> <Text>

7.3.3 Context and rationale for study exclusion criteria

Table 5:

Operational Definitions of Exclusion Criteria

Criterion Details Order of application Assessment window Care settings Code Type Diagnosis position Applied to study populations: Measurement characteristics/ validation Source of algorithm
<Text> <Text> <Text> <Text> <Text> <Text> <Text> <Text> <Text> <Text>

7.4 Variables

7.4.1 Context and rationale for exposure(s) of interest

Algorithm to define duration of exposure effect:

Table 6:

Operational Definitions of Exposure

Exposure group name(s) Details Washout window Assessment window Care settings Code Type Diagnosis position Applied to study populations: Incident with respect to... Measurement characteristics/ validation Source of algorithm
<Text> <Text> <Text> <Text> <Text> <Text> <Text> <Text> <Text> <Text> <Text>

7.4.2 Context and rationale for outcome(s) of interest

Table 7:

Operational Definitions of Outcome

Outcome name Details Primary outcome? Type of outcome Washout window Care settings Code Type Diagnosis position Applied to study populations: Measurement characteristics/ validation Source of algorithm
<Text> <Text> <Text> <Text> <Text> <Text> <Text> <Text> <Text> <Text> <Text>

7.4.3 Context and rationale for follow up

Table 8:

Operational Definitions of Follow up

Time point Select all that apply Specify
Follow up start <Text> <Text>
Follow up end <Text> <Text>
Date of outcome <Text> <Text>
Date of death <Text> <Text>
End of observation in data <Text> <Text>
Day X following index date <Text> <Text>
End of study period <Text> <Text>
End of exposure <Text> <Text>
Date of add to/switch from exposure <Text> <Text>
Other date <Text> <Text>

7.4.4 Context and rationale for covariates (confounding variables and effect modifiers, e.g. risk factors, comorbidities, comedications)

Table 9:

Operational Definitions of Covariates

Characteristic Details Type of variable Assessment window Care settings Code Type Diagnosis position Applied to study populations: Measurement characteristics/ validation Source of algorithm
<Text> <Text> <Text> <Text> <Text> <Text> <Text> <Text> <Text> <Text>

7.5 Data analysis

7.5.1 Context and rationale for analysis plan

7.5.1.1 A. Primary analysis

Table 10: Primary, secondary, and subgroup analysis specification

(a)

A. Primary analysis

Analysis element Specification
Hypothesis: <Text>
Exposure contrast: <Text>
Outcome: <Text>
Analytical software <Text>
Model(s): <Text>
Conofunding adjustment method Name method and provide relevant details, e.g. bivariate, multivariable, propensity score matching (specify matching algorithm ratio and caliper), propensity score weighting (specify weight formula, trimming, truncation), propensity score stratification (specify strata definition), other
Missing data methods Name method and provide relevant details, e.g. missing indicators, complete case, last value carried forward, multiple imputation (specify model/variables), other.
Subgroup Analyses List all subgroups
(b)

B. Secondary analysis

Analysis element Specification
Hypothesis: <Text>
Exposure contrast: <Text>
Outcome: <Text>
Analytical software <Text>
Model(s): <Text>
Conofunding adjustment method Name method and provide relevant details, e.g. bivariate, multivariable, propensity score matching (specify matching algorithm ratio and caliper), propensity score weighting (specify weight formula, trimming, truncation), propensity score stratification (specify strata definition), other
Missing data methods Name method and provide relevant details, e.g. missing indicators, complete case, last value carried forward, multiple imputation (specify model/variables), other.
Subgroup Analyses List all subgroups
Table 11:

Sensitivity analyses – rationale, strengths and limitations

Analysis What is being varied? Why (expected learning)? Strengths of the sensitivity analysis compared to primary Limitations of the sensitivity analysis compared to primary
<Text> <Text> <Text> <Text> <Text>

7.6 Data sources

7.6.1 Context and rationale for data sources

Reason for selection:

Strengths of data source(s):

Limitations of data source(s):

Data source provenance/curation:

Table 12:

Metadata about data sources and software

Data element Data 1 Data 2 Data 3
Data Sources: <Text> <Text> <Text>
Study Period: <Text> <Text> <Text>
Eligibile Cohort Entry Period: <Text> <Text> <Text>
Data version (or date of last update): <Text> <Text> <Text>
Data sampling/extraction criteria: <Text> <Text> <Text>
Type(s) of data: <Text> <Text> <Text>
Data linkage <Text> <Text> <Text>
Conversion to CDM: <Text> <Text> <Text>
Software for data management: <Text> <Text> <Text>

7.7 Data management

7.8 Quality control

7.9 Study size and feasibility

8 Limitation of the methods

9 Protection of human subjects

10 Reporting of adverse events

11 References

1.
Wang SV, Pottegård A, Crown W, et al. HARmonized Protocol Template to Enhance Reproducibility of Hypothesis Evaluating Real-World Evidence Studies on Treatment Effects: A Good Practices Report of a Joint ISPE/ISPOR Task Force. Value in Health 2022; 25: 1663–1672. doi:10.1016/j.jval.2022.09.001.
2.
Wang SV, Pottegård A, Crown W, et al. HARmonized Protocol Template to Enhance Reproducibility of hypothesis evaluating real-world evidence studies on treatment effects: A good practices report of a joint ISPE/ISPOR task force. Pharmacoepidemiology and Drug Safety 2022; 32: 44–55. doi:10.1002/pds.5507.
3.
Graphical depiction of longitudinal study designs in health care databases. Annals of Internal Medicine 2019; 170: 398–406. doi:10.7326/M18-3079.
4.
Lund LC, Hallas J, Wang SV. Online tool to create publication ready graphical depictions of longitudinal study design implemented in healthcare databases. Pharmacoepidemiology and Drug Safety 2021; 30: 982–982. doi:10.1002/pds.5241.

12 Appendices

13 Session info

13.1 Loaded packages

  package loadedversion
dplyr dplyr 1.1.1
forcats forcats 1.0.0
ggplot2 ggplot2 3.4.2
gt gt 0.9.0
here here 1.0.1
lubridate lubridate 1.9.2
purrr purrr 1.0.1
readr readr 2.1.4
stringr stringr 1.5.0
tibble tibble 3.2.1
tidyr tidyr 1.3.0
tidyverse tidyverse 2.0.0

13.2 Session info

R version 4.2.1 (2022-06-23)

Platform: x86_64-apple-darwin17.0 (64-bit)

locale: en_US.UTF-8||en_US.UTF-8||en_US.UTF-8||C||en_US.UTF-8||en_US.UTF-8

attached base packages: stats, graphics, grDevices, datasets, utils, methods and base

other attached packages: gt(v.0.9.0), here(v.1.0.1), lubridate(v.1.9.2), forcats(v.1.0.0), stringr(v.1.5.0), dplyr(v.1.1.1), purrr(v.1.0.1), readr(v.2.1.4), tidyr(v.1.3.0), tibble(v.3.2.1), ggplot2(v.3.4.2) and tidyverse(v.2.0.0)

loaded via a namespace (and not attached): tidyselect(v.1.2.0), xfun(v.0.38), pander(v.0.6.5), colorspace(v.2.1-0), vctrs(v.0.6.0), generics(v.0.1.3), htmltools(v.0.5.4), yaml(v.2.3.7), utf8(v.1.2.3), rlang(v.1.1.0), pillar(v.1.9.0), glue(v.1.6.2), withr(v.2.5.0), bit64(v.4.0.5), sessioninfo(v.1.2.2), lifecycle(v.1.0.3), munsell(v.0.5.0), gtable(v.0.3.3), htmlwidgets(v.1.6.2), evaluate(v.0.20), knitr(v.1.42), tzdb(v.0.3.0), fastmap(v.1.1.1), parallel(v.4.2.1), fansi(v.1.0.4), Rcpp(v.1.0.10), renv(v.0.16.0), scales(v.1.2.1), vroom(v.1.6.1), jsonlite(v.1.8.4), bit(v.4.0.5), hms(v.1.1.3), digest(v.0.6.31), stringi(v.1.7.12), grid(v.4.2.1), rprojroot(v.2.0.3), cli(v.3.6.0), tools(v.4.2.1), magrittr(v.2.0.3), sass(v.0.4.5), crayon(v.1.5.2), pkgconfig(v.2.0.3), xml2(v.1.3.3), timechange(v.0.2.0), rmarkdown(v.2.20), rstudioapi(v.0.14), R6(v.2.5.1) and compiler(v.4.2.1)

13.3 Repositories

  • repos:

    CRAN
    https://cran.rstudio.com

14 Change log

Detailed change log based on previous commits.

Mon, 3 Jul 2023 15:14:41 -0400
Changes made by: jweberpals@bwh.harvard.edu 
Commit hash:  bf124db
Changes made: adjusted paths

Mon, 3 Jul 2023 14:55:18 -0400
Changes made by: jweberpals@bwh.harvard.edu 
Commit hash:  f05af92
Changes made: improved documentation and added more HARPER templates

Mon, 1 May 2023 20:08:12 -0400
Changes made by: jweberpals@bwh.harvard.edu 
Commit hash:  60bae9b
Changes made: added session info and version number

Mon, 24 Apr 2023 14:32:47 -0400
Changes made by: jweberpals@bwh.harvard.edu 
Commit hash:  69ec58d
Changes made: added references

Thu, 20 Apr 2023 16:16:33 -0400
Changes made by: jweberpals@bwh.harvard.edu 
Commit hash:  ac5ff1f
Changes made: echo is only false for protocol

Tue, 18 Apr 2023 15:16:00 -0400
Changes made by: jweberpals@bwh.harvard.edu 
Commit hash:  48390ee
Changes made: styling of tables

Mon, 17 Apr 2023 17:12:00 -0400
Changes made by: jweberpals@bwh.harvard.edu 
Commit hash:  bfb71b5
Changes made: added index

Mon, 17 Apr 2023 16:58:04 -0400
Changes made by: jweberpals@bwh.harvard.edu 
Commit hash:  4705250
Changes made: some modifications

Mon, 17 Apr 2023 16:14:43 -0400
Changes made by: jweberpals@bwh.harvard.edu 
Commit hash:  c0f1b13
Changes made: with format gt

Mon, 17 Apr 2023 15:24:42 -0400
Changes made by: jweberpals@bwh.harvard.edu 
Commit hash:  106faf2
Changes made: attempt  to balance html and pdf output using gt

Sun, 16 Apr 2023 19:20:26 -0400
Changes made by: jweberpals@bwh.harvard.edu 
Commit hash:  f0bde2b
Changes made: first HARPER draft; TODO: Tables in pdf

Sun, 16 Apr 2023 19:12:50 -0400
Changes made by: jweberpals@bwh.harvard.edu 
Commit hash:  34b0c71
Changes made: initial commit