From 411be99bc92371cc46a3cf6c4a55c73c5304b56f Mon Sep 17 00:00:00 2001 From: Will King Date: Fri, 30 Aug 2024 12:52:55 -0700 Subject: [PATCH] began rewriting introduction --- Latex/Paper/sections/01.1_introduction.tex | 98 +++++++++++++++++++++ Latex/Paper/sections/01_introduction.tex | 99 ++-------------------- 2 files changed, 107 insertions(+), 90 deletions(-) create mode 100644 Latex/Paper/sections/01.1_introduction.tex diff --git a/Latex/Paper/sections/01.1_introduction.tex b/Latex/Paper/sections/01.1_introduction.tex new file mode 100644 index 0000000..2241ca2 --- /dev/null +++ b/Latex/Paper/sections/01.1_introduction.tex @@ -0,0 +1,98 @@ +\documentclass[../Main.tex]{subfiles} +\graphicspath{{\subfix{Assets/img/}}} + +\begin{document} +% hook - what makes drugs expensive? Mention high failure rate +% describe current research +% - Examine mechanisms by which clinical trials fail. +% - Mention data +% - Results +How to best address the high cost of pharmaceuticals is a crucial health +and fiscal policy question that has been debated for +decades. +Due to the complicated legal and competitive landscape, unintended consequences +are common +\cite{vandergronde_addressingchallengehighpriced_2017}. +One essential step to introduce a novel pharmaceutical - or even +to begin selling a generic compound - is to establish that the drug as packaged and sold will +have acceptable safety and efficacy profiles. +When evaluating these compounds in a clinical trial, multiple outcomes are possible: +\begin{enumerate} + \item The compound demonstrates sufficient safety and efficacy, and proceeds in the appoval process. + \label{Item:EndSuccess} + \item The compound fails to demonstrate sufficient safety and efficacy, and the approval process halts. + \label{Item:EndFail} + \item The trial is terminated before it can acheive one of the first two + outcomes, for reasons unrelated to safety and efficacy concerns. + \label{Item:Terminate} +\end{enumerate} + + +\begin{table} + \caption{Potential States of Knowledge from a clinical trial}\label{tab:StatesOfKnowledge} + \begin{center} + \begin{tabular}{p{0.15\textwidth} p{0.2\textwidth}||p{0.25\textwidth}|p{0.25\textwidth}|} + \cline{3-4} + \multicolumn{2}{c|}{Drug-Indication Match} & safe and efficacious & not safe or not efficatious \\ + \hline + \hline + \multirow{2}{0.15\textwidth}{Operations} & Success & Known good & Known bad \\ + \cline{2-4} + & Failure & \multicolumn{2}{c|}{Unkown} \\ + \cline{2-4} + \end{tabular} + \end{center} +\end{table} + + +\begin{table} + \caption{Clinical Trial end states}\label{tab:ClinicalTrialEndStates} + \begin{center} + \begin{tabular}{p{0.15\textwidth} p{0.2\textwidth}||p{0.25\textwidth}|p{0.25\textwidth}|} + \cline{3-4} + \multicolumn{2}{c|}{Drug-Indication Match} & safe and efficacious & not safe or not efficatious \\ + \hline + \hline + \multirow{2}{0.15\textwidth}{Operations} & Success & Completion & Completion or Termination \\ + \cline{2-4} + & Failure & \multicolumn{2}{c|}{Termination} \\ + \cline{2-4} + \end{tabular} + \end{center} +\end{table} + +While it is known that pharmaceutical companies withdraw some drugs from +their development pipeline due to commercialization concerns +( +\cite{khmelnitskaya_competition_2021} +and +\cite{van_der_gronde_addressing_2017} +), there are likely unseen +effects that might affect the overall drug pipleline. +One of these is the concern that when there are already approved therapies on +the market, patients might be loath to enroll in clinical trials, +causing the trial to fail for reasons unrelated to the scientific or +commercial viability of the therapy. + + +To adequately guide public policy it is crucial that robust, causally-identified +statistical models are available to describe the interaction between +various players within the space. + +This work endeavors to estimate the change in probability of successful completion +of a clinical trial due to the existence of alternative drugs on the market. +In particular, it seeks to establish whether such an impact is mediated +by enrollment patterns or is caused more directly. + + +The paper proceeds as follows: a brief literature review in \cref{SEC:LiteratureReview}, +a description of the caual model in \cref{SEC:CausalIdentification}, +followed by a description of the data (\cref{SEC:Data}) and the +econometric model (\cref{SEC:EconometricModel}). +Preliminary results are presented in \cref{SEC:Results} and a discussion +of proposed improvements is included in \cref{SEC:Improvements}. + + + + +\end{document} diff --git a/Latex/Paper/sections/01_introduction.tex b/Latex/Paper/sections/01_introduction.tex index 2241ca2..24bebe5 100644 --- a/Latex/Paper/sections/01_introduction.tex +++ b/Latex/Paper/sections/01_introduction.tex @@ -2,97 +2,16 @@ \graphicspath{{\subfix{Assets/img/}}} \begin{document} -% hook - what makes drugs expensive? Mention high failure rate -% describe current research -% - Examine mechanisms by which clinical trials fail. -% - Mention data -% - Results -How to best address the high cost of pharmaceuticals is a crucial health -and fiscal policy question that has been debated for -decades. -Due to the complicated legal and competitive landscape, unintended consequences -are common -\cite{vandergronde_addressingchallengehighpriced_2017}. -One essential step to introduce a novel pharmaceutical - or even -to begin selling a generic compound - is to establish that the drug as packaged and sold will -have acceptable safety and efficacy profiles. -When evaluating these compounds in a clinical trial, multiple outcomes are possible: -\begin{enumerate} - \item The compound demonstrates sufficient safety and efficacy, and proceeds in the appoval process. - \label{Item:EndSuccess} - \item The compound fails to demonstrate sufficient safety and efficacy, and the approval process halts. - \label{Item:EndFail} - \item The trial is terminated before it can acheive one of the first two - outcomes, for reasons unrelated to safety and efficacy concerns. - \label{Item:Terminate} -\end{enumerate} - - -\begin{table} - \caption{Potential States of Knowledge from a clinical trial}\label{tab:StatesOfKnowledge} - \begin{center} - \begin{tabular}{p{0.15\textwidth} p{0.2\textwidth}||p{0.25\textwidth}|p{0.25\textwidth}|} - \cline{3-4} - \multicolumn{2}{c|}{Drug-Indication Match} & safe and efficacious & not safe or not efficatious \\ - \hline - \hline - \multirow{2}{0.15\textwidth}{Operations} & Success & Known good & Known bad \\ - \cline{2-4} - & Failure & \multicolumn{2}{c|}{Unkown} \\ - \cline{2-4} - \end{tabular} - \end{center} -\end{table} - - -\begin{table} - \caption{Clinical Trial end states}\label{tab:ClinicalTrialEndStates} - \begin{center} - \begin{tabular}{p{0.15\textwidth} p{0.2\textwidth}||p{0.25\textwidth}|p{0.25\textwidth}|} - \cline{3-4} - \multicolumn{2}{c|}{Drug-Indication Match} & safe and efficacious & not safe or not efficatious \\ - \hline - \hline - \multirow{2}{0.15\textwidth}{Operations} & Success & Completion & Completion or Termination \\ - \cline{2-4} - & Failure & \multicolumn{2}{c|}{Termination} \\ - \cline{2-4} - \end{tabular} - \end{center} -\end{table} - -While it is known that pharmaceutical companies withdraw some drugs from -their development pipeline due to commercialization concerns -( -\cite{khmelnitskaya_competition_2021} -and -\cite{van_der_gronde_addressing_2017} -), there are likely unseen -effects that might affect the overall drug pipleline. -One of these is the concern that when there are already approved therapies on -the market, patients might be loath to enroll in clinical trials, -causing the trial to fail for reasons unrelated to the scientific or -commercial viability of the therapy. - - -To adequately guide public policy it is crucial that robust, causally-identified -statistical models are available to describe the interaction between -various players within the space. - -This work endeavors to estimate the change in probability of successful completion -of a clinical trial due to the existence of alternative drugs on the market. -In particular, it seeks to establish whether such an impact is mediated -by enrollment patterns or is caused more directly. - - -The paper proceeds as follows: a brief literature review in \cref{SEC:LiteratureReview}, -a description of the caual model in \cref{SEC:CausalIdentification}, -followed by a description of the data (\cref{SEC:Data}) and the -econometric model (\cref{SEC:EconometricModel}). -Preliminary results are presented in \cref{SEC:Results} and a discussion -of proposed improvements is included in \cref{SEC:Improvements}. - +Developing new, effective pharmaceutical compounds is a fundamentally difficult task. +Starting with challenges identifying promising treatment targets and potential compounds, to ensuring the drug can be properly delivered within the body, the scientific work that needs to go well is massive. +The regulatory and market conditions in which they exist add to this difficulty. +For example, regulations are designed to reduce the number of drugs released to market +with significan issues, such as in the case of VIOXX \cite{krumholz_whathavewe_2007} +or the Perdue Pharma scandal \cite{officepublicaffairsjusticedepartment_2020}. +These regulations, such as clinical trial standards \todo{add citation to clinical trials here}, +increase the costs of developing new drugs, adding to the business conserns already present, including +competitors already in the market or close to entering and the overall demand to address a given condition. \end{document}