added current presentation draft

Latex/Presentation/presentation.tex

@@ -14,7 +14,7 @@
 %%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%
 
 %----------------------------------------------------------------------------------------
-%	PACKAGES AND THEMES
+%    PACKAGES AND THEMES
 %----------------------------------------------------------------------------------------
 
 \documentclass[xcolor=dvipsnames,aspectratio=169]{beamer}
@@ -32,7 +32,7 @@
 
 
 %----------------------------------------------------------------------------------------
-%	TITLE PAGE
+%    TITLE PAGE
 %----------------------------------------------------------------------------------------
 
 \title[Clinical Trials]{Pharmaceutial competitors and their effect on clinical trial completion} 
@@ -89,13 +89,13 @@ Washington State University \\ % Your institution for the title page
 
     The FDA requires clinical trials before approving new drug compounds
     \begin{itemize}
-	    \item Pre-registered design
+        \item Pre-registered design
-	    \item Updated regularly on clinicaltrials.gov
+        \item Updated regularly on clinicaltrials.gov
-	    \item Often requires an oversight board.
+        \item Often requires an oversight board.
-	    \item Goal is to prove efficacy and safety of a compound/dosage/route.
+        \item Goal is to prove efficacy and safety of a compound/dosage/route.
-	    \item A new drug candidate (NDC) must complete 3 phases of clinical trials before approval.
+        \item A new drug candidate (NDC) must complete 3 phases of clinical trials before approval.
-	    \item Phases are reviewed with FDA.
+        \item Phases are reviewed with FDA.
-	    \item Not all clinical trials are for new drugs.
+        \item Not all clinical trials are for new drugs.
     \end{itemize}
 \end{frame}
 %-----------------------------
@@ -112,16 +112,16 @@ Washington State University \\ % Your institution for the title page
 \begin{frame}
     \frametitle{Questions of Interest}
 
-	\begin{itemize}
+    \begin{itemize}
-		\item How do the competitors on the market affect clinical trial completion?
+        \item How do the competitors on the market affect clinical trial completion?
-		\item How is this effect moderated by the enrollment of participants?
+        \item How is this effect moderated by the enrollment of participants?
-	\end{itemize}
+    \end{itemize}
 \end{frame}
 %-------------------------------
 \begin{frame}
     \frametitle{Audience Questions}
 
-	\center{What can I clarify?}
+    \center{What can I clarify?}
 \end{frame}
 %-------------------------------
 %-------------------------------------------------------------------------------------
@@ -141,63 +141,63 @@ Washington State University \\ % Your institution for the title page
 %-------------------------------
 \begin{frame}[shrink=10] %evil option is helpful here.
     \frametitle{How do clinical trials proceed?}
-	\begin{columns}[T]
+    \begin{columns}[T]
-	\begin{column}{0.5\textwidth}
+    \begin{column}{0.5\textwidth}
     What does a complete trial look like.
-	\begin{enumerate}
+    \begin{enumerate}
-		\item Study sponsor comes up with design
+        \item Study sponsor comes up with design
-		\item Apply for NCT ID from ClinicalTrials.gov
+        \item Apply for NCT ID from ClinicalTrials.gov
-		\item Begin enrolling participants
+        \item Begin enrolling participants
-		\item Update ClinicalTrials.gov to recruit
+        \item Update ClinicalTrials.gov to recruit
-		\item Close Enrollment
+        \item Close Enrollment
-		\item Update ClinicalTrials.gov as not recruiting*
+        \item Update ClinicalTrials.gov as not recruiting*
-		\item Reach primary objectives
+        \item Reach primary objectives
-		\item Update ClinicalTrials.gov as complete
+        \item Update ClinicalTrials.gov as complete
-		\item Reach secondary objectives
+        \item Reach secondary objectives
-		\item Update ClinicalTrials.gov with more information
+        \item Update ClinicalTrials.gov with more information
-	\end{enumerate}
+    \end{enumerate}
-	\end{column}
+    \end{column}
-	\begin{column}{0.5\textwidth}
+    \begin{column}{0.5\textwidth}
     What does an incomplete trial look like?
-	\begin{enumerate}
+    \begin{enumerate}
-		\item Study sponsor comes up with design
+        \item Study sponsor comes up with design
-		\item Apply for NCT ID from ClinicalTrials.gov
+        \item Apply for NCT ID from ClinicalTrials.gov
-		\item Begin enrolling participants
+        \item Begin enrolling participants
-		\item Update ClinicalTrials.gov to advertise
+        \item Update ClinicalTrials.gov to advertise
-		\item Run into issues: 
+        \item Run into issues: 
-			\begin{itemize}
+            \begin{itemize}
-				\item Safety
+                \item Safety
-				\item Efficacy
+                \item Efficacy
-				\item Profitability
+                \item Profitability
-				\item Feasiblity (enrollment, PI leaves, etc.)
+                \item Feasiblity (enrollment, PI leaves, etc.)
-			\end{itemize}
+            \end{itemize}
-		\item Close Enrollment*
+        \item Close Enrollment*
-		\item Decide to terminate clinical trial.
+        \item Decide to terminate clinical trial.
-		\item Update ClinicalTrials.gov as terminated.
+        \item Update ClinicalTrials.gov as terminated.
-	\end{enumerate}
+    \end{enumerate}
-	\end{column}
+    \end{column}
-	\end{columns}
+    \end{columns}
 \end{frame}
 %-------------------------------
 \begin{frame}
     \frametitle{ClinicalTrials.gov}
-	Thus ClinicalTrials.gov becomes an (append only) repository of 
+    Thus ClinicalTrials.gov becomes an (append only) repository of 
-	the ``current'' status of clincal trials.
+    the ``current'' status of clincal trials.
 
 
-	As it is designed to help faciltate enrollment in clinical trials, 
+    As it is designed to help faciltate enrollment in clinical trials, 
-	the record includes important information such as 
+    the record includes important information such as 
 
-	\begin{itemize}
+    \begin{itemize}
-		\item drugs
+        \item drugs
-		\item study arms
+        \item study arms
-		\item conditions
+        \item conditions
-		\item expected and final enrollment figures
+        \item expected and final enrollment figures
-		\item current status
+        \item current status
-	\end{itemize}
+    \end{itemize}
 
-	ClinicalTrials.gov also reports the ``history'' from previous
+    ClinicalTrials.gov also reports the history from previous
-	updates.
+    updates.
 \end{frame}
 
 %-------------------------------
@@ -216,7 +216,111 @@ Washington State University \\ % Your institution for the title page
 % - Introduce backdoor criterion
 %--------------------------------
 
+%-------------------------------
+\begin{frame}
+    \frametitle{Framing my Questions}
+    Two potential causes of trial termination include 
+    \begin{enumerate}
+        \item Alternative (competitor) treatments exist
+            \begin{itemize}
+                \item reduces future profitability.
+                \item reduces incentives to enroll as participants.
+            \end{itemize}
+        \item It can be difficult to recruit patients
+            \begin{itemize}
+                \item Are there few patients?
+                \item Are potential participants choosing other alternatives?
+            \end{itemize}
+    \end{enumerate}
+    Overall this can be described graphically as:
+
+    INSERT IMAGE OF 4 NODES HERE
+
+
+\end{frame}
+%-------------------------------
+\begin{frame}
+    \frametitle{Causal Identification: Backdoor Criterion}
+    %Discuss the two different effects: total effect, direct effects
+
+    \begin{columns}
+    \begin{column}{0.5\textwidth}
+        Total Effect of Competitors
+
+        INSERT TOTAL EFFECT GRAPH
+    \end{column}
+    \begin{column}{0.5\textwidth}
+        Direct Effects of Competitors and Enrollment
+
+        INSERT DIRECT EFFECT GRAPH
+    \end{column}
+    \end{columns}
+\end{frame}
+
+%-------------------------------
+\begin{frame}
+    \frametitle{Rephrasing Questions}
+    To rephrase my questions
+    \begin{enumerate}
+        \item How large is the total effect of increasing the number of competing drugs on completing clinical trials?
+        \item How large is the direct effect of increasing the number of competing drugs on completing clincial trials?
+    \end{enumerate}
+\end{frame}
+%-------------------------------
+\begin{frame}
+    \frametitle{Additional Concerns}
+    %Confounders 
+    Of course, there are other confounding relationships
+    \begin{enumerate}
+        \item Population Effects
+        \item Fundamental Safety and Efficacy of compound/dosage/route
+    \end{enumerate}
+
+\end{frame}
+%-------------------------------
+\begin{frame}
+    \frametitle{Complete graph}
+    %introduce backdoor criterion
+
+    INSERT COMPLETE GRAPH HERE
+
+\end{frame}
+%-------------------------------
+\begin{frame}
+    \frametitle{Causal Identification: Backdoor Criterion}
+    %introduce backdoor criterion
+
+    \cite{PEARLYYYY} developed a method of verifying causal identification from DAGs like the one I presented.
+
+    Of particular interest is the rule called the Backdoor criterion:
+
+    INSERT DESCRIPTION OF THE BACK DOOR CRITERION    
+
+
+\end{frame}
+%-------------------------------
+\begin{frame}
+    \frametitle{Sufficent Adjustment Set}
+    %introduce backdoor criterion
+
+    INSERT COMPLETE GRAPH HERE with adjustment set highlighted
 
+\end{frame}
+%-------------------------------
+\begin{frame}
+    \frametitle{Sufficent Adjustment Set}
+    %introduce backdoor criterion
+
+    Thus the required adjustment set includes:
+
+    \begin{itemize}
+        \item Population Measures
+        \item Safety and Efficacy Measures
+        \item INSERT MORE
+    \end{itemize}
+
+
+\end{frame}
 %-------------------------------
 \begin{frame}
     \frametitle{Questions?}
@@ -236,6 +340,84 @@ Washington State University \\ % Your institution for the title page
 % - Data Sizes
 %--------------------------------
 
+%-------------------------------
+\begin{frame}
+    \frametitle{Data Sources}
+    %TODO: add citations
+    Data sources
+    \begin{itemize}
+        \item ClinicalTrials.gov
+            \begin{itemize}
+                \item AACT-CTTI
+                \item Scraping historical snapshots
+            \end{itemize}
+        \item ICD-10 (CMS and WHO)
+        \item IHME Global Burden of Disease
+        \item Structured Product Labels
+        \item USP Drug Classification
+        \item Drugs@FDA: RxNav / RxNorm / MeSH
+    \end{itemize}
+\end{frame}
+%-------------------------------
+\begin{frame}
+    \frametitle{Linking data}
+    %
+    The following linking process was used:
+    \begin{enumerate}
+        \item AACT trials to snapshots (internal ID)
+        \item AACT trials to ICD-10 (hand match)
+        \item ICD-10 to IHME (IHME)
+        \item Snapshots to drug brands (RxNorm/RxNav/MeSh, SPL)
+        \item AACT to USP DC alternates (RxNorm, USP DC, hand match)
+    \end{enumerate}
+
+\end{frame}
+%-------------------------------
+\begin{frame}
+    \frametitle{Measures of Causes and Effects}
+    
+    \begin{itemize}
+        \item Final Status: Measured from AACT - status when trial is over.
+        \item Competitors on Market: Measured by the number of drugs
+            \begin{itemize}
+                \item with same active ingredients (at the time of the snapshot)
+                \item sharing the USP DC category and class (in 2023)
+            \end{itemize}
+        \item Enrollment: Measured by enrollment status at the snapshot level.
+    \end{itemize}
+
+\end{frame}
+%-------------------------------
+\begin{frame}
+    \frametitle{Adjustment set}
+    \begin{itemize}
+        \item Population Measures
+            \begin{itemize}
+                \item IHME Global Disease Burden: QUALYs, spread over 5 levels of the Social Development Index
+            \end{itemize}
+        \item Beliefs about safety \& efficacy: Restricted to Phase 3 trials.
+        \item Disease Type: Hierarchal parameters in model
+    \end{itemize}
+
+    Note the implicit conditioning on trials treating diseases with IHME data\footnote{
+        IHME does not track data for W61.62XD: Struck by duck, subsequent encounter
+    }.
+
+\end{frame}
+%-------------------------------
+\begin{frame}
+    \frametitle{Other Details}
+
+    Other Trial Selection Criteria
+    \begin{itemize}
+        \item Interventional Study
+        \item Involved an FDA Regulated Drug
+        \item Phase 3 trial
+        \item Started after 2010-01-01
+        \item Ended before 2022-01-01
+    \end{itemize}
+
+\end{frame}
 %-------------------------------
 \begin{frame}
     \frametitle{Questions?}
@@ -317,7 +499,7 @@ Washington State University \\ % Your institution for the title page
 \begin{frame}
     \frametitle{Final Questions}
 
-	\center{\huge{Time is yours to ask any remaining questions.}}
+    \center{\huge{Time is yours to ask any remaining questions.}}
 \end{frame}
 %-------------------------------------------------------------------------------------
 %%%%%%%%%%%%%%%%%%%% Appendicies %%%%%%%%%%%%%%%%%%%%%%%%