Merge pull request #5 from erikwestlund/protocol

Rmd protocol for SemaglutideNaion study package

.gitignore

@@ -2,3 +2,4 @@
 .Rhistory
 .RData
 .Ruserdata
+.idea/*

README.md

@@ -10,7 +10,7 @@ Estimation of risk of NAION and other vision disorders from exposure to semaglut
 - Study lead forums tag: **[[Cindy X. Cai]](https://forums.ohdsi.org/u/cindyxcai)**
 - Study start date: **-**
 - Study end date: **-**
-- Protocol: **<a href="docs/Semaglutide and NAION Research Protocol.pdf">docs/Semaglutide and NAION Research Protocol.pdf</a>**
+- Protocol: **<a href="docs/Protocol.html</a>**
 - Publications: **-**
 - Results explorer: **-**
 

SemaglutideNaion.Rproj

@@ -11,3 +11,7 @@ Encoding: UTF-8
 
 RnwWeave: Sweave
 LaTeX: pdfLaTeX
+
+BuildType: Package
+PackageUseDevtools: Yes
+PackageInstallArgs: --no-multiarch --with-keep.source

docs/Abbreviations.Rmd

@@ -0,0 +1,30 @@
+```{r abbreviations, echo=FALSE, message=FALSE}
+abbreviations <- readr::read_delim(col_names = FALSE, delim = ";", trim_ws = TRUE, file = "
+  NAION; Non-arteritic ischemic optic neuropathy
+  DR; Diabetic retinopathy
+  PDR; Proliferative diabetic retinopathy
+  DME; Diabetic macular edema
+  VR; Vitreoretinal
+  GLP-1 RA; Glucagon-like peptide 1 receptor agonist
+  SGLT2; Sodium-glucose cotransporter -2
+  DPP4; Dipeptidyl peptidase-4
+  T2DM; Type 2 diabetes mellitus
+  VO; Vein occlusion
+  AO; Artery occlusion
+  AMD; Age-related macular degeneration
+  GCA; Giant cell arteritis
+  EASE; Expected Absolute Systematic Error
+  MDRR; Minimum Detectable Relative Risk
+  OHDSI; Observational Health Data Sciences and Informatics
+  ARVO; The Association for Research in Vision and Ophthalmology
+")
+
+tab <- kable(abbreviations, col.names = NULL, linesep = "", booktabs = TRUE)
+
+if (knitr::is_latex_output()) {
+  tab %>% kable_styling(latex_options = c("striped", "hold_position"),
+                        font_size = latex_table_font_size)
+} else {
+  tab %>% kable_styling(bootstrap_options = "striped")
+}
+```

docs/Abstract.Rmd

@@ -0,0 +1,12 @@
+**Background**: Despite its cardiovascular and kidney benefits, semaglutide has been recently linked to severe ophthalmic complications including non-arteritic ischemic optic neuropathy (NAION) as well as worsening of diabetic retinopathy (DR).
+
+**Purpose**: To estimate the risk of these ophthalmic complications, NAION and DR worsening, with semaglutide use compared with other non-GLP-1 RA medications (including empagliflozin, sitagliptin, and glipizide) among adults with type 2 diabetes mellitus.
+
+**Design**: Retrospective study employing an active comparator, new-user cohort design
+
+**Subjects**: Adults (≥ 18 years) with type 2 diabetes mellitus who are new users of semaglutide (a GLP-1 RA), dulaglutide (a GLP-1 RA), exenatide (a GLP-1 RA), empagliflozin (an SGLT2 inhibitor), sitagliptin (a DPP4 inhibitor), or glipizide (a sulfonylurea)
+
+**Methods**: Patients receiving semaglutide will be compared to propensity score matched patients with each of the other GLP-1 RA and non-GLP-1 RA medications. We will deploy the large-scale propensity score method that adjusts for a comprehensive range of baseline characteristics. Cox models will be used to compare the time to NAION or DR worsening between patients who receive semaglutide with patients who receive empagliflozin, sitagliptin, and glipizide. Similar comparisons will be made between the other GLP-1 RA (namely dulaglutide and exenatide) with each of the comparators.
+
+**Conclusions**: Clarifying the risk of severe ophthalmic complications associated with semaglutide (and other GLP-1 RA) by 1) characterizing the incidence in the exposed population, and 2) estimating the risk of exposure will help guide the appropriate use of this medication.
+

docs/Appendix.Rmd

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+# Study Population Cohort Definitions
+
+```{r study-population-cohorts, echo=FALSE, results="asis", warning=FALSE, message=FALSE}
+
+printCohortDefinitionFromNameAndJson(name = "Persons with Type 2 diabetes mellitus and no prior T1DM or secondary diabetes",
+                                     json = SqlRender::readSql("../inst/cohorts/17795_Persons with Type 2 diabetes mellitus and no prior T1DM or secondary diabetes.json"),
+                                     withConcepts = TRUE)
+
+printCohortDefinitionFromNameAndJson(name = "New user of semaglutide as 2nd-line treatment with prior T2DM and prior metformin",
+                                     json = SqlRender::readSql("../inst/cohorts/17793_New user of semaglutide as 2nd-line treatment with prior T2DM and prior metformin.json"),
+                                     withConcepts = TRUE)
+
+printCohortDefinitionFromNameAndJson(name = "New user of semaglutide as 2nd-line treatment with prior T2DM Dec2017-Jan2020",
+                                     json = SqlRender::readSql("../inst/cohorts/17809_New user of semaglutide as 2nd-line treatment with prior T2DM Dec2017-Jan2020.json"),
+                                     withConcepts = TRUE)
+
+printCohortDefinitionFromNameAndJson(name = "New user of semaglutide as 2nd-line treatment with prior T2DM Feb2020-Jun2021",
+                                     json = SqlRender::readSql("../inst/cohorts/17810_New user of semaglutide as 2nd-line treatment with prior T2DM Feb2020-Jun2021.json"),
+                                     withConcepts = TRUE)
+
+printCohortDefinitionFromNameAndJson(name = "New user of semaglutide as 2nd-line treatment with prior T2DM Jul2021-Dec2023",
+                                     json = SqlRender::readSql("../inst/cohorts/17811_New user of semaglutide as 2nd-line treatment with prior T2DM Jul2021-Dec2023.json"),
+                                     withConcepts = TRUE)
+
+printCohortDefinitionFromNameAndJson(name = "New user of semaglutide with prior T2DM and prior metformin and no insulin",
+                                     json = SqlRender::readSql("../inst/cohorts/17803_New user of semaglutide with prior T2DM and prior metformin and no insulin.json"),
+                                     withConcepts = TRUE)
+
+printCohortDefinitionFromNameAndJson(name = "New user of dulaglutide as 2nd-line treatment with prior T2DM and prior metformin",
+                                     json = SqlRender::readSql("../inst/cohorts/17796_New user of dulaglutide as 2nd-line treatment with prior T2DM and prior metformin.json"),
+                                     withConcepts = TRUE)
+
+printCohortDefinitionFromNameAndJson(name = "New user of dulaglutide with prior T2DM and prior metformin and no insulin",
+                                     json = SqlRender::readSql("../inst/cohorts/17807_New user of dulaglutide with prior T2DM and prior metformin and no insulin.json"),
+                                     withConcepts = TRUE)
+
+printCohortDefinitionFromNameAndJson(name = "New user of exenatide as 2nd-line treatment with prior T2DM and prior metformin",
+                                     json = SqlRender::readSql("../inst/cohorts/17797_New user of exenatide as 2nd-line treatment with prior T2DM and prior metformin.json"),
+                                     withConcepts = TRUE)
+
+printCohortDefinitionFromNameAndJson(name = "New user of exenatide with prior T2DM and prior metformin and no insulin",
+                                     json = SqlRender::readSql("../inst/cohorts/17808_New user of exenatide with prior T2DM and prior metformin and no insulin.json"),
+                                     withConcepts = TRUE)
+
+printCohortDefinitionFromNameAndJson(name = "New user of empagliflozin as 2nd-line treatment with prior T2DM and prior metformin",
+                                     json = SqlRender::readSql("../inst/cohorts/17798_New user of empagliflozin as 2nd-line treatment with prior T2DM and prior metformin.json"),
+                                     withConcepts = TRUE)
+
+printCohortDefinitionFromNameAndJson(name = "New user of empagliflozin as 2nd-line treatment with prior T2DM Dec2017-Jan2020",
+                                     json = SqlRender::readSql("../inst/cohorts/17812_New user of empagliflozin as 2nd-line treatment with prior T2DM Dec2017-Jan2020.json"),
+                                     withConcepts = TRUE)
+
+printCohortDefinitionFromNameAndJson(name = "New user of empagliflozin as 2nd-line treatment with prior T2DM Feb2020-Jun2021",
+                                     json = SqlRender::readSql("../inst/cohorts/17813_New user of empagliflozin as 2nd-line treatment with prior T2DM Feb2020-Jun2021.json"),
+                                     withConcepts = TRUE)
+
+printCohortDefinitionFromNameAndJson(name = "New user of empagliflozin as 2nd-line treatment with prior T2DM Jul2021-Dec2023",
+                                     json = SqlRender::readSql("../inst/cohorts/17814_New user of empagliflozin as 2nd-line treatment with prior T2DM Jul2021-Dec2023.json"),
+                                     withConcepts = TRUE)
+
+printCohortDefinitionFromNameAndJson(name = "New user of empagliflozin with prior T2DM and prior metformin and no insulin",
+                                     json = SqlRender::readSql("../inst/cohorts/17804_New user of empagliflozin with prior T2DM and prior metformin and no insulin.json"),
+                                     withConcepts = TRUE)
+
+printCohortDefinitionFromNameAndJson(name = "New user of sitagliptin as 2nd-line treatment with prior T2DM and prior metformin",
+                                     json = SqlRender::readSql("../inst/cohorts/17799_New user of sitagliptin as 2nd-line treatment with prior T2DM and prior metformin.json"),
+                                     withConcepts = TRUE)
+
+printCohortDefinitionFromNameAndJson(name = "New user of sitagliptin with prior T2DM and prior metformin and no insulin",
+                                     json = SqlRender::readSql("../inst/cohorts/17805_New user of sitagliptin with prior T2DM and prior metformin and no insulin.json"),
+                                     withConcepts = TRUE)
+
+printCohortDefinitionFromNameAndJson(name = "New user of glipizide as 2nd-line treatment with prior T2DM and prior metformin",
+                                     json = SqlRender::readSql("../inst/cohorts/17801_New user of glipizide as 2nd-line treatment with prior T2DM and prior metformin.json"),
+                                     withConcepts = TRUE)
+
+printCohortDefinitionFromNameAndJson(name = "New user of glipizide with prior T2DM and prior metformin and no insulin",
+                                     json = SqlRender::readSql("../inst/cohorts/17806_New user of glipizide with prior T2DM and prior metformin and no insulin.json"),
+                                     withConcepts = TRUE)
+
+```
+
+# Exposure Cohort Definitions
+
+
+```{r exposure-cohorts, echo=FALSE, results="asis", warning=FALSE, message=FALSE}
+printCohortDefinitionFromNameAndJson(name = "Semaglutide (GLP-1RA) exposure",
+                                     json = SqlRender::readSql("../inst/cohorts/17816_semaglutide exposures.json"),
+                                     withConcepts = TRUE)
+
+printCohortDefinitionFromNameAndJson(name = "Dulaglutide (GLP-1RA) exposure",
+                                     json = SqlRender::readSql("../inst/cohorts/17817_dulaglutide exposures.json"),
+                                     withConcepts = TRUE)
+
+printCohortDefinitionFromNameAndJson(name = "Exenatide (GLP-1RA) exposure",
+                                     json = SqlRender::readSql("../inst/cohorts/17818_exenatide exposures.json"),
+                                     withConcepts = TRUE)
+
+printCohortDefinitionFromNameAndJson(name = "Empagliflozin (SGLT2 inhibitor) exposure",
+                                     json = SqlRender::readSql("../inst/cohorts/17819_empagliflozin exposures.json"),
+                                     withConcepts = TRUE)
+
+printCohortDefinitionFromNameAndJson(name = "Sitagliptin (DPP4 inhibitor) exposure",
+                                     json = SqlRender::readSql("../inst/cohorts/17820_sitagliptin exposures.json"),
+                                     withConcepts = TRUE)
+
+printCohortDefinitionFromNameAndJson(name = "Glipizide (Sulfonylurea) exposure",
+                                     json = SqlRender::readSql("../inst/cohorts/17821_glipizide exposures.json"),
+                                     withConcepts = TRUE)
+
+```
+
+# Outcome Cohort Definitions
+
+```{r outcome-cohorts, echo=FALSE, results="asis", warning=FALSE, message=FALSE}
+
+printCohortDefinitionFromNameAndJson(name = "Nonarteric anterior ischemic neuropathy with index date correction and 2dxGCA",
+                                     json = SqlRender::readSql("../inst/cohorts/17760_Nonarteric anterior ischemic neuropathy with index date correction and 2dxGCA.json"),
+                                     withConcepts = TRUE)
+
+printCohortDefinitionFromNameAndJson(name = "Nonarteric anterior ischemic neuropathy with index date correction and 2nd dx and 2dxGCA",
+                                     json = SqlRender::readSql("../inst/cohorts/17761_Nonarteric anterior ischemic neuropathy with index date correction and 2nd dx and 2dxGCA.json"),
+                                     withConcepts = TRUE)
+
+printCohortDefinitionFromNameAndJson(name = "Proliferative diabetic retinopathy",
+                                     json = SqlRender::readSql("../inst/cohorts/17706_Proliferative diabetic retinopathy.json"),
+                                     withConcepts = TRUE)
+
+printCohortDefinitionFromNameAndJson(name = "Treatment-requiring Diabetic Retinopathy or Macular Edema",
+                                     json = SqlRender::readSql("../inst/cohorts/17815_Treatment-requiring Diabetic Retinopathy or Macular Edema.json"),
+                                     withConcepts = TRUE)
+
+printCohortDefinitionFromNameAndJson(name = "Treatment-requiring Diabetic Retinopathy or Macular Edema including vitrectomy",
+                                     json = SqlRender::readSql("../inst/cohorts/17788_Treatment-requiring Diabetic Retinopathy or Macular Edema including vitrectomy.json"),
+                                     withConcepts = TRUE)
+
+```
+
+# Negative Control Concepts
+
+\captionsetup{labelformat=empty}
+
+```{r, echo=FALSE, warning=FALSE, message=FALSE}
+negative_controls <- readr::read_csv("../inst/negativeControlOutcomes.csv") %>%
+  select(conceptid, conceptname) %>%
+  rename("Concept ID" = conceptid, "name" = conceptname) %>%
+  arrange(name)
+
+colnames(negative_controls) <- c("", "Concept ID")
+
+tab <- kable(negative_controls, booktabs = TRUE, linesep = "", longtable = TRUE,
+      caption = "Negative outcome controls specified through condition occurrences that map to (a descendent of) the indicated concept ID") %>%
+  kable_styling(bootstrap_options = "striped", latex_options = "striped")
+
+if (knitr::is_latex_output()) {
+  tab %>%
+    column_spec(1, width = "40em") %>%
+    column_spec(2, width = "15em") %>%
+    kable_styling(font_size = latex_table_font_size,
+                  latex_options = c("repeat_header"),
+                  repeat_header_continued = "\\textit{(Continued on Next Page...)}")
+
+} else {
+  tab
+}
+```

docs/Disclosures.Rmd

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+This study is undertaken within Observational Health Data Sciences and Informatics (OHDSI), an open collaboration.
+