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113 lines
4.6 KiB
TeX
113 lines
4.6 KiB
TeX
\documentclass[../Main.tex]{subfiles}
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\graphicspath{{\subfix{Assets/img/}}}
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\begin{document}
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% Clinical Trials Background Outline
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% - ClinicalTrials.gov
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% - Clincial trial progression
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To understand how my administrative clinical trial data is obtained
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and what it can be used for,
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let's take a look at how trial investigators record data on
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\url{ClinicalTrials.gov} operate.
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Figure \ref{Fig:Stages} illuistrates the process I describe below.
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During the Pre-Trial period the trial investigators will design the trial,
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choose primary and secondary objectives,
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and decide on how many participants they need to enroll.
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Once they have decided on these details, they post the trial to \url{ClinicalTrials.com}
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and decide on a date to begin enrolling trial participants.
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If the investigators decide to not continue with the trial before enrolling any participants,
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the trial is marked as ``Withdrawn''.
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On the other hand, if they begin enrolling participants, there are two methods to do so.
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The first is to enter a general ``Recruiting'' state, where patients attempt to enroll.
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The second is to enter an "Enrollment by invitation only" state.
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After a trial has enrolled their participants, they wil typically move to an
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"Active, not recruiting" state to inform potential participants that they are
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not recruiting.
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Finally, when the investigators have obtained enough data to achieve their primary
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objective, the clinical trial will be closed, and marked as ``Completed'' in
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\url{ClinicalTrials.gov}
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If the trial is closed before achieving the primary objective, the trial is
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marked as ``Terminated'' on
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\url{ClinicalTrials.gov}.
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\begin{figure}%[H] %use [H] to fix the figure here.
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\includegraphics[width=\textwidth]{../assets/img/ClinicalTrialStagesAndStatuses}
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\par \small
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Diamonds represent decision points while
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Squares represent states of the clinical trial and Rhombuses represend data obtained by the trial.
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\caption[Clinical Trial Stages and Progression]{Clinical Trial Stages and Progression}
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\label{Fig:Stages}
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\end{figure}
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Note the information we obtain about the trial from the final status:
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``Withdrawn'', ``Terminated'', or ``Completed''.
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Although \cite{khm} describes a clinical failure due to safety or efficacy as a
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\textit{scientific} failure, it is better described as a compound failure.
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Discovering that a compound doesn't work as hoped is not a failure but the whole
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purpose of the clinical trials process.
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On the other hand, when a trial terminates early due to reasons
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other than safety or efficacy concerns, the trial operator does not learn
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if the drug is effective or safe.
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This is a knowledge-gathering failure where the trial operator
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did not learn if the drug was effective or not.
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I prefer describing a clinical trial as being terminated for
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\begin{itemize}
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\item Safety or Efficacy concerns
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\item Strategic concerns
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\item Operational concerns.
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\end{itemize}
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Unfortunately it can be difficult to know why a given trial was terminated,
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in spite of the fact that upon termination, trials typically record a
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description of \textit{a single} reason for the clinical trial termination.
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This doesn't necessarily list all the reasons contributing to the trial termination and may not exist for a given trial.
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For example, if a Principle Investigator leaves for another institution
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(terminating the trial), is this decison affected by
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a safety or efficacy concern,
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a new competitor on the market,
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difficulting recruiting participants,
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or a lack of financial support from the study sponsor?
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Estimating the impact of different problems that trials face from these
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low-information, post-hoc signals is insufficient.
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For this reason, I use clinical trial progression to estimate effects.
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\todo{not sure if this is the best place for this.}
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As a trial goes through the different stages of recruitment, the investigators
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update the records on ClinicalTrials.gov.
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Even though there are only a few times that investigators are required
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to update this information, it tends to be updated somewhat regularly as it is
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a way to communicate with potential enrollees.
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When a trial is first posted, it tends to include information
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such as planned enrollment,
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planned end dates,
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the sites at which it is being conducted,
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the diseases that it is investigating,
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the drugs or other treatments that will be used,
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the experimental arms that will be used,
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and who is sponsoring the trial.
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As enrollment is opened and closed and sites are added or removed,
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investigators will update the status and information
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to help doctors and potential participants understand whether they should apply.
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\end{document}
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