From aaaf1531682c3d928105a479518ea44335078457 Mon Sep 17 00:00:00 2001 From: will king Date: Tue, 12 Nov 2024 20:29:15 -0800 Subject: [PATCH] saving current work and plans --- Latex/Paper/outline3.txt | 41 +++++++++++ .../sections/03_CausalIdentification.tex | 48 ++++++------ Latex/Paper/sections/10_CausalStory.tex | 4 + .../sections/12_clinical_trial_background.tex | 73 +++++++------------ 4 files changed, 95 insertions(+), 71 deletions(-) create mode 100644 Latex/Paper/outline3.txt diff --git a/Latex/Paper/outline3.txt b/Latex/Paper/outline3.txt new file mode 100644 index 0000000..933b54c --- /dev/null +++ b/Latex/Paper/outline3.txt @@ -0,0 +1,41 @@ +How do I begin work on stuff + +- next step is causal story. key points include + - we are trying to separate strategic and operational concerns. (why is this a difficult problem?) + - we can't trust what we are told + - terminations could be due to safety, strategic, or operational concerns. + - explaining confounding between + -population/market and market conditions. + - market conditions and enrollment. + - population/market and enrollment. + - describe other confounders + - safety and effectiveness + - duration <--> enrollment/termination + - Condition + - Decision to procede with Phase III trial + - How do I handle this? +- Introduce Do-Calculus + - DAG model + - What do I need to control for, in some form or other? +- Introduce Data + - Clinical Trial Progression + - AACT gives us information on + - terminated/completed status + - compound-indication pairs + - MeSH/RxNorm links + - Snapshots + - Market Conditions + - can't directly measure alternate treatments/standards of care. + - Can get measures of USP - formulary alternatives + - Can get number of generics or brand names with same drug. + - Population Sizes + - IHME Global Burden of Disease dataset. Best measure of impact of a given disease category. + - DALY's + - How much data do I have? +- Econometric model + - for a given state, what is the probability it will terminate? + - more accurately for my dist-diff analysis: for a given state, what is the distribution of the probabilities it will terminate? + - basic bernoulli-logistic model, linear in parameters. + - What are the specific things I am looking at? + - number of competing treatments. + - delaying close of enrollment. diff --git a/Latex/Paper/sections/03_CausalIdentification.tex b/Latex/Paper/sections/03_CausalIdentification.tex index d54f9bc..cb56c08 100644 --- a/Latex/Paper/sections/03_CausalIdentification.tex +++ b/Latex/Paper/sections/03_CausalIdentification.tex @@ -2,31 +2,33 @@ \graphicspath{{\subfix{Assets/img/}}} \begin{document} -% Introduce clinicaltrials.gov -% - Describe different statuses -% - status flowchart -% Introduce causal model -% - Diagram -% - List each node and what they influence (and why) -% Begin Discussing Data -% - Where did I get data for each node? +% % Introduce clinicaltrials.gov +% % - Describe different statuses +% % - status flowchart +% % Introduce causal model +% % - Diagram +% % - List each node and what they influence (and why) +% % Begin Discussing Data +% % - Where did I get data for each node? +% +% When any clinical trial is conducted, it goes through three distinct stages: +% pre-trial, active, and decision to conclude. +% In figure \ref{Fig:Stages}, you can see the component parts of each stage. +% +% \begin{figure}[H] %use [H] to fix the figure here. +% \includegraphics[width=\textwidth]{../assets/img/ClinicalTrialStagesAndStatuses} +% \caption{Model of Statuses} +% \label{Fig:Stages} +% \end{figure} +% +% In the pre-trial stage, the sponsoring organization chooses to run the trial, +% they register the trial on \url{ClinicalTrials.gov}, and then decide if they +% will begin enrollment. +% Many registered trials are withdrawn at this point, before the trial has opened +% for enrollment. +% Once enrollment has opened -When any clinical trial is conducted, it goes through three distinct stages: -pre-trial, active, and decision to conclude. -In figure \ref{Fig:Stages}, you can see the component parts of each stage. -\begin{figure}[H] %use [H] to fix the figure here. - \includegraphics[width=\textwidth]{../assets/img/ClinicalTrialStagesAndStatuses} - \caption{Model of Statuses} - \label{Fig:Stages} -\end{figure} - -In the pre-trial stage, the sponsoring organization chooses to run the trial, -they register the trial on \url{ClinicalTrials.gov}, and then decide if they -will begin enrollment. -Many registered trials are withdrawn at this point, before the trial has opened -for enrollment. -Once enrollment has opened Because running randomized experiments on companies running clinical trials is unlikely to to happen anytime soon, diff --git a/Latex/Paper/sections/10_CausalStory.tex b/Latex/Paper/sections/10_CausalStory.tex index 3d8d9a2..874a5f5 100644 --- a/Latex/Paper/sections/10_CausalStory.tex +++ b/Latex/Paper/sections/10_CausalStory.tex @@ -3,6 +3,10 @@ \begin{document} +Begin by talking about goal, what does it mean? This might need some work prior to give more background. + +%%%%% \/\/\/\/\/ OLD STUFF \/\/\/\/\/ + Because running experiments on companies running clinical trials is not going to happen anytime soon, causal identification will depend on creating a structural causal model. diff --git a/Latex/Paper/sections/12_clinical_trial_background.tex b/Latex/Paper/sections/12_clinical_trial_background.tex index 3686e68..fe16b8f 100644 --- a/Latex/Paper/sections/12_clinical_trial_background.tex +++ b/Latex/Paper/sections/12_clinical_trial_background.tex @@ -14,7 +14,8 @@ % - % - -To understand how my administrative clinical trial is obtained, +To understand how my administrative clinical trial data is obtained +and what it can be used for, 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. @@ -39,7 +40,7 @@ marked as ``Terminated'' on \url{ClinicalTrials.gov}. -\begin{figure}[H] %use [H] to fix the figure here. +\begin{figure}%[H] %use [H] to fix the figure here. \includegraphics[width=\textwidth]{../assets/img/ClinicalTrialStagesAndStatuses} \par \small Diamonds represent decision points while @@ -62,55 +63,31 @@ 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 +As a trial goes through the different stages of recruitment, the investigators +update the records on ClinicalTrials.gov. +Even though there are only a few times that investigators are required +to update this information, it tends to be updated somewhat regularly as it is +a way to communicate with potential enrollees. +When a trial is first posted, it tends to include information +such as planned enrollment, +planned end dates, +the sites at which it is being conducted, +the diseases that it is investigating, +the drugs or other treatments that will be used, +the experimental arms that will be used, +and who is sponsoring the trial. +As enrollment is opened and closed and sites are added or removed, +investigators will update the status and information +to help doctors and potential participants understand whether they should apply. -% \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}