diff --git a/Latex/Paper/Main.tex b/Latex/Paper/Main.tex index 0505c32..35f8ffc 100644 --- a/Latex/Paper/Main.tex +++ b/Latex/Paper/Main.tex @@ -51,6 +51,8 @@ completion of clinical trials\\ \small{Preliminary Draft}} % \section{Literature Review}\label{SEC:LiteratureReview} % %--------------------------------------------------------------- % \subfile{sections/05_LitReview} +\section{Clincal Trial Background}\label{SEC:ClinicalTrials} +\subfile{sections/12_clinical_trial_background} %--------------------------------------------------------------- \section{Causal Story and Data}\label{SEC:Data} diff --git a/Latex/Paper/sections/11_intro_and_lit.tex b/Latex/Paper/sections/11_intro_and_lit.tex index e39f6b9..57121d6 100644 --- a/Latex/Paper/sections/11_intro_and_lit.tex +++ b/Latex/Paper/sections/11_intro_and_lit.tex @@ -176,7 +176,7 @@ or other studies prove that the trial requires a protocol change. This paper proposes the first model to separate the causal effects of market conditions (a strategic concern) from the effects of -participant enrollment (an operational concern). +participant enrollment (an operational concern) on Phase III Clinical trials. This will allow me to answer the questions: \begin{itemize} \item What is the marginal effect on trial completion of an additional @@ -193,7 +193,7 @@ Finally I'll review the results and conclusion in sections \ref{SEC:Results} and \ref{SEC:Conclusion} -respectively +respectively. % \subsection{Market incentives and drug development} % %%%%%%%%% What do we know about drug development incentives? diff --git a/Latex/Paper/sections/12_clinical_trial_background.tex b/Latex/Paper/sections/12_clinical_trial_background.tex new file mode 100644 index 0000000..3686e68 --- /dev/null +++ b/Latex/Paper/sections/12_clinical_trial_background.tex @@ -0,0 +1,116 @@ +\documentclass[../Main.tex]{subfiles} +\graphicspath{{\subfix{Assets/img/}}} + +\begin{document} + +% Clinical Trials Background Outline +% - ClinicalTrials.gov +% - Clincial trial progression +% - +% - +% - +% - +% - +% - +% - + +To understand how my administrative clinical trial is obtained, +let's take a look at how trial investigators record data on +\url{ClinicalTrials.gov} operate. +Figure \ref{Fig:Stages} illuistrates the process I describe below. +During the Pre-Trial period the trial investigators will design the trial, +choose primary and secondary objectives, +and decide on how many participants they need to enroll. +Once they have decided on these details, they post the trial to \url{ClinicalTrials.com} +and decide on a date to begin enrolling trial participants. +If the investigators decide to not continue with the trial before enrolling any participants, +the trial is marked as ``Withdrawn''. +On the other hand, if they begin enrolling participants, there are two methods to do so. +The first is to enter a general ``Recruiting'' state, where patients attempt to enroll. +The second is to enter an "Enrollment by invitation only" state. +After a trial has enrolled their participants, they wil typically move to an +"Active, not recruiting" state to inform potential participants that they are +not recruiting. +Finally, when the investigators have obtained enough data to achieve their primary +objective, the clinical trial will be closed, and marked as ``Completed'' in +\url{ClinicalTrials.gov} +If the trial is closed before achieving the primary objective, the trial is +marked as ``Terminated'' on +\url{ClinicalTrials.gov}. + + +\begin{figure}[H] %use [H] to fix the figure here. + \includegraphics[width=\textwidth]{../assets/img/ClinicalTrialStagesAndStatuses} + \par \small + Diamonds represent decision points while + Squares represent states of the clinical trial and Rhombuses represend data obtained by the trial. + \caption[Clinical Trial Stages and Progression]{Clinical Trial Stages and Progression} + \label{Fig:Stages} +\end{figure} + +Note the information we obtain about the trial from the final status: +``Withdrawn'', ``Terminated'', or ``Completed''. +Although \cite{khm} describes a clinical failure due to safety or efficacy as a +\textit{scientific} failure, it is better described as a compound failure. +Discovering that a compound doesn't work as hoped is not a failure but the whole +purpose of the clinical trials process. +On the other hand, when a trial terminates early due to reasons +other than safety or efficacy concerns, the trial operator does not learn +if the drug is effective or safe. +This is a true failure in that we did not learn if the drug was effective or not. +Unfortunately, although termination documentation typically includes a +description of a reason for the clinical trial termination, this doesn't necessarily +list all the reasons contributing to the trial termination and may not exist for a given trial. + +% SHOULD I EXPLAIN THE CLINICAL TRIALS DATA, i.e. AACT and SCRAPING EFFORT YET? +% For this reason we use administrative data, the records of clinical trial states, to track how trials proceed. +% There is also the issue of confounding between different + + + +% \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} + + +\end{document}