JobMarketPaper/Latex/Presentation/presentation.tex

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\documentclass[xcolor=dvipsnames,aspectratio=169]{beamer}


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\input{../assets/preambles/FormattingPreamble.tex}
\input{../assets/preambles/TikzitPreamble.tex}
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\input{../assets/preambles/BibPreamble.tex}
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%----------------------------------------------------------------------------------------
%    TITLE PAGE
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\title[Clinical Trials]{Pharmaceutial competitors and their effect on clinical trial completion} 

\author{Will King} % Your name
\institute[WSU] % Your institution as it will appear on the bottom of every slide, may be shorthand to save space
{
Washington State University \\ % Your institution for the title page
\medskip
\textit{william.f.king@wsu.edu} % Your email address
}
\date{\today} % Date, can be changed to a custom date





\begin{document}
\begin{frame}
\titlepage % Print the title page as the first slide
\end{frame}


%-------------------------------
\begin{frame}
    \frametitle{Introduction}

\end{frame}
%-------------------------------
\begin{frame}[allowframebreaks] %Allow frame breaks
\frametitle{Overview} % Table of contents slide, comment this out to remove it
\tableofcontents 
\end{frame}
%-------------------------------

%-------------------------------------------------------------------------------------
%%%%%%%%%%%%%%%%%%%% Introduction and Background %%%%%%%%%%%%%%%%%%%%%%%%
\section{Background}
% TOC
% - Background on drug process
% - Literature on clinical trials
% - My questions
%-------------------------------------------------------------------------------------

%-------------------------------
\begin{frame}
    \frametitle{Clinical Trials and Drug develoment}
    % add info about trials
    % - Requirements (pre registered design [2007], updated "regularly" on clinicaltrials.gov)
    % - Phases (1,2,3,4, mixed)
    % - Safety and Ethicas (oversight boards, restrictions on payments)
    % - Approval processes (biologics vs small-molecule)
    % add info about drugs

    The FDA requires clinical trials before approving new drug compounds
    \begin{itemize}
        \item Pre-registered design
        \item Updated regularly on clinicaltrials.gov
        \item Often requires an oversight board.
        \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 Phases are reviewed with FDA.
        \item Not all clinical trials are for new drugs.
    \end{itemize}
\end{frame}
%-----------------------------
\begin{frame}
    \frametitle{Literature}
    \begin{itemize}
        \item Ekaterina
        \item Adams
        \item 
    \end{itemize}

\end{frame}
%-----------------------------
\begin{frame}
    \frametitle{Questions of Interest}

    \begin{itemize}
        \item How do the competitors on the market affect clinical trial completion?
        \item How is this effect moderated by the enrollment of participants?
    \end{itemize}
\end{frame}
%-------------------------------
\begin{frame}
    \frametitle{Audience Questions}

    \center{What can I clarify?}
\end{frame}
%-------------------------------
%-------------------------------------------------------------------------------------
%%%%%%%%%%%%%%%%%%%% Causality and Data %%%%%%%%%%%%%%%%%%%%%%%%
\section{Causal Story and Data}
% TOC
% - Causal Story (no subsection)
%    - Clinical trials: targets specific drug/condition combination.
%    - Enrollment process: patients counsel with providers
%    - Trials terminate if unsafe, ineffective, unprofitable, or cannot enroll patients
%    - Ethical concerns exist throughout.
%    - This is complicated by the fact that the experiment reveals information over time.
% - Formalization
% - Data Sources
%-------------------------------------------------------------------------------------

%-------------------------------
\begin{frame}[shrink=10] %evil option is helpful here.
    \frametitle{How do clinical trials proceed?}
    \begin{columns}[T]
    \begin{column}{0.5\textwidth}
    What does a complete trial look like.
    \begin{enumerate}
        \item Study sponsor comes up with design
        \item Apply for NCT ID from ClinicalTrials.gov
        \item Begin enrolling participants
        \item Update ClinicalTrials.gov to recruit
        \item Close Enrollment
        \item Update ClinicalTrials.gov as not recruiting*
        \item Reach primary objectives
        \item Update ClinicalTrials.gov as complete
        \item Reach secondary objectives
        \item Update ClinicalTrials.gov with more information
    \end{enumerate}
    \end{column}
    \begin{column}{0.5\textwidth}
    What does an incomplete trial look like?
    \begin{enumerate}
        \item Study sponsor comes up with design
        \item Apply for NCT ID from ClinicalTrials.gov
        \item Begin enrolling participants
        \item Update ClinicalTrials.gov to advertise
        \item Run into issues: 
            \begin{itemize}
                \item Safety
                \item Efficacy
                \item Profitability
                \item Feasiblity (enrollment, PI leaves, etc.)
            \end{itemize}
        \item Close Enrollment*
        \item Decide to terminate clinical trial.
        \item Update ClinicalTrials.gov as terminated.
    \end{enumerate}
    \end{column}
    \end{columns}
\end{frame}
%-------------------------------
\begin{frame}
    \frametitle{ClinicalTrials.gov}
    Thus ClinicalTrials.gov becomes an (append only) repository of 
    the ``current'' status of clincal trials.


    As it is designed to help faciltate enrollment in clinical trials, 
    the record includes important information such as 

    \begin{itemize}
        \item drugs
        \item study arms
        \item conditions
        \item expected and final enrollment figures
        \item current status
    \end{itemize}

    ClinicalTrials.gov also reports the history from previous
    updates.
\end{frame}

%-------------------------------
\begin{frame}
    \frametitle{Questions?}

\end{frame}
%-------------------------------
%--------------------------------
%%%%%%%%%%%%%%%%%%%% Causal Formalization
\subsection{Formalization}
% - Introduce basic triangle
%    - discuss total vs direct effects
%    - 
% - Add confounders and controls
% - 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?}

\end{frame}
%-------------------------------
%--------------------------------
%%%%%%%%%%%%%%%%%%%% Data sources
\subsection{Data Sources}
% TOC
% - Main Data Sources
%    - ClinicalTrials.gov and AACT
%    - IHME Burden of Disease
%    - Marketing Data
%    - MeSH, RxNorm/RxNav
% - How did I Link Data Sources
% - 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?}

\end{frame}
%-------------------------------
%-------------------------------------------------------------------------------------
%%%%%%%%%%%%%%%%%%%% Analysis %%%%%%%%%%%%%%%%%%%%%%%%
\section{Analysis}
% TOC
% - Review questions and datasets to use for each
% - 
% - 
%-------------------------------------------------------------------------------------

%-------------------------------
\begin{frame}
    \frametitle{Questions?}

\end{frame}
%--------------------------------
%%%%%%%%%%%%%%%%%%%% Econometric Model
\subsection{Econometric Model}
% - Present model per effect
% - 
% - 
%--------------------------------

%-------------------------------
\begin{frame}
    \frametitle{Questions?}

\end{frame}
%--------------------------------
%%%%%%%%%%%%%%%%%%%% Results
\subsection{Results}
%--------------------------------
%--------------------------------
\subsubsection{Total Effect}
% - Review Parameter Values
%    - hyperparameters
%        - Table of MLE
%        - Distributions
%    - betas
%        - Table of MLE
%        - Distributions
% - Review Posterior Prediction for interventions
%--------------------------------
%-------------------------------
\begin{frame}
    \frametitle{Questions?}

\end{frame}
%-------------------------------
%--------------------------------
\subsubsection{Direct Effects}
% - Review Parameter Values
%    - hyperparameters
%        - Table of MLE
%        - Distributions
%    - betas
%        - Table of MLE
%        - Distributions
% - Review Posterior Prediction for interventions
%--------------------------------

%-------------------------------
\begin{frame}
    \frametitle{Questions?}

\end{frame}
%-------------------------------
%-------------------------------------------------------------------------------------
%%%%%%%%%%%%%%%%%%%% Conclusion %%%%%%%%%%%%%%%%%%%%%%%%
\section{Conclusion}
%-------------------------------------------------------------------------------------

%-------------------------------
\begin{frame}
    \frametitle{Final Questions}

    \center{\huge{Time is yours to ask any remaining questions.}}
\end{frame}
%-------------------------------------------------------------------------------------
%%%%%%%%%%%%%%%%%%%% Appendicies %%%%%%%%%%%%%%%%%%%%%%%%
\section{Appendices}
%-------------------------------------------------------------------------------------

%-------------------------------
\begin{frame}
    \frametitle{Equilibrium in the Money Market}
    Interest rates are the price of money, so we need to compare 
    interest rates to the quantity of money demanded. 


    \begin{figure}
%        \tikzfig{../Assets/tikzit/}
        \label{FIG:costs}
        \caption{Money Market Equilibrium}
    \end{figure}
\end{frame}
%-------------------------------
\end{document} 
%=========================================
%\begin{frame}
%    \frametitle{MarginalRevenue}
%    \begin{figure}
%        \tikzfig{../Assets/owned/ch8_MarginalRevenue}
%        \includegraphics[height=\textheight]{../Assets/copyrighted/KrugmanObsterfeldMeliz_fig8-7.jpg}
%        \label{FIG:costs}
%        \caption{Average Cost Curve as firms enter.}
%    \end{figure}
%\end{frame}
%-------------------------------
%\begin{frame}
%    \frametitle{Columns}
%     \begin{columns}
%        \begin{column}{0.5\textwidth}
%        \end{column}
%        \begin{column}{0.5\textwidth}
%               \begin{figure}
%                   \tikzfig{../Assets/owned/ch7_EstablishedAdvantageExample2}
%                   \label{FIG:costs}
%                   \caption{Setting the Stage}
%               \end{figure}
%        \end{column}
%     \end{columns}
%\end{frame}
% %---------------------------------------------------------------