\documentclass[../Main.tex]{subfiles}
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\begin{document}

% Clinical Trials Background Outline
% - ClinicalTrials.gov
% - Clincial trial progression
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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the trial is marked as ``Withdrawn''.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``Withdrawn'', ``Terminated'', or ``Completed''.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}
