From 209977f4ff0d68179ccf47dbae94de71a3aacb3b Mon Sep 17 00:00:00 2001 From: Will King Date: Wed, 4 Oct 2023 16:26:23 -0700 Subject: [PATCH] added current presentation draft --- Latex/Presentation/presentation.tex | 306 ++++++++++++++++++++++------ 1 file changed, 244 insertions(+), 62 deletions(-) diff --git a/Latex/Presentation/presentation.tex b/Latex/Presentation/presentation.tex index 2395a4c..75d45f5 100644 --- a/Latex/Presentation/presentation.tex +++ b/Latex/Presentation/presentation.tex @@ -14,7 +14,7 @@ %%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%% %---------------------------------------------------------------------------------------- -% PACKAGES AND THEMES +% PACKAGES AND THEMES %---------------------------------------------------------------------------------------- \documentclass[xcolor=dvipsnames,aspectratio=169]{beamer} @@ -32,7 +32,7 @@ %---------------------------------------------------------------------------------------- -% TITLE PAGE +% TITLE PAGE %---------------------------------------------------------------------------------------- \title[Clinical Trials]{Pharmaceutial competitors and their effect on clinical trial completion} @@ -89,13 +89,13 @@ Washington State University \\ % Your institution for the title page 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. + \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} %----------------------------- @@ -112,16 +112,16 @@ Washington State University \\ % Your institution for the title page \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} + \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?} + \center{What can I clarify?} \end{frame} %------------------------------- %------------------------------------------------------------------------------------- @@ -141,63 +141,63 @@ Washington State University \\ % Your institution for the title page %------------------------------- \begin{frame}[shrink=10] %evil option is helpful here. \frametitle{How do clinical trials proceed?} - \begin{columns}[T] - \begin{column}{0.5\textwidth} + \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} + \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} + \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. + 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 + 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} + \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. + ClinicalTrials.gov also reports the history from previous + updates. \end{frame} %------------------------------- @@ -216,7 +216,111 @@ Washington State University \\ % Your institution for the title page % - 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?} @@ -236,6 +340,84 @@ Washington State University \\ % Your institution for the title page % - 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?} @@ -317,7 +499,7 @@ Washington State University \\ % Your institution for the title page \begin{frame} \frametitle{Final Questions} - \center{\huge{Time is yours to ask any remaining questions.}} + \center{\huge{Time is yours to ask any remaining questions.}} \end{frame} %------------------------------------------------------------------------------------- %%%%%%%%%%%%%%%%%%%% Appendicies %%%%%%%%%%%%%%%%%%%%%%%%