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\graphicspath{{\subfix{Assets/img/}}}
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\begin{document}
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% Introduce clinicaltrials.gov
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% - Describe different statuses
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% - status flowchart
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% Introduce causal model
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% - Diagram
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% - List each node and what they influence (and why)
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% Begin Discussing Data
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% - Where did I get data for each node?
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Because running experiments on companies running clinical trials is not going
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to happen anytime soon, causal identification will depend on creating a
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structural causal model.
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In \cref{Fig:CausalModel} I diagram the directed acyclic graph that describes
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the data generating model.
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The proposed data generating model consists of a decision maker, the study
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sponsor, who must decide whether to let a trial run to completion or terminate
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Because running randomized experiments on companies running clinical trials
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is unlikely to to happen anytime soon,
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causal identification will depend on observational methods.
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I use the do-calculus approach developed by Judea Pearl
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\cite{pearl_CausalityModels_2009}
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to describe what affects the success of a Phase III clinical trial.
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I then use that model to derive the econometric model capable of estimating
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the effect of extending the recruiting period or of having an additional
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competing drug.
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% In \cref{Fig:CausalModel} I diagram the directed acyclic graph that describes
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% the data generating model.
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The proposed data generating model consists of a decision maker
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-- the study sponsor --
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who must decide whether to let a trial run to completion or terminate
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the trial early.
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While receiving updates regarding the status of the trial, they ask questions
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such as:
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While receiving updates regarding the status of the trial, they try to
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answer questions such as:
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\begin{itemize}
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\item Do I need to terminate the trial due to safety incidents?
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\item Does it appear that the drug is effective enough to achieve our
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goals, justifying continuing the trial?
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\item Does it appear that the drug is effective?
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\item Are we recruiting enough participants to achive the statistical
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results we need?
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\item Does the current market conditions and expectations about returns on
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\item Does the current market conditions and expectations about
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returns on
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investment justify the expenditures we are making?
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\end{itemize}
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When appropriate, the study sponsor terminates the trial.
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If there are not enough issues to terminate the trial, it continues until it
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is completed.
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Althought I treat this as a single agent, in reality, there are multiple
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stakeholders involved in chosing whether the trial should continue, including
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those running the trial (which may be a separate firm),
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the company developing the drug, additional rightsholders,
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or funding organizations.
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% When appropriate, the study sponsor terminates the trial.
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% If there are not enough issues to terminate the trial, it continues until it
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% is completed.
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In the United States, clinical trials are required by law to be registered on
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\url{ClinicalTrials.gov}, where they are made available to the public.
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Trials must be registered
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%
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While conducting a trial, the safety and efficacy of a drug are driven by
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fundamental pharmacokinetic properties of the compounds.
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@ -36,19 +67,25 @@ Of course, these decisions are both affected by the specific condition being
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treated due to differences in the severity of the symptoms.
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When a trial has been started, it comes time to recruit participancts.
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Participants frequently depend on the advice of their physician when deciding
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The enrollment of participants in a trial depends on a few factors.
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Participants usually depend on the advice of their physician when deciding
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to join a trial or not.
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As these physicians have a duty to seek their patients best interest; they, along
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with their patients will evaluate if the previously observed safety and efficacy
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results justify joining the trial over using current standard treatments.
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Thus the current market conditions may affect the rate at which participants
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enroll in the trial.
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results justify joining the trial in contrast to using the current standard
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of care.
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Thus enrollment rates are influenced by the treatments currently on the market.
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Recruitment can also be hindered if disease has a low impact
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-- in which participants might have little incentive to join --
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or if there are few people who have the disease.
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The overall impact of the disease also influences whether or not there are
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already drugs on the market to treat that disease.
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The enrollment of participants in a trial depends on a few other factors.
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The condition or disease of interest and how it progresses will determine how long
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recruitiment will be held open versus just an observation of treatment arms.
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Aditionally, a trial that has already reached a high enough enrollment will often
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close recruitment by switching to an "Active, not recruiting" stage to manage costs.
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close recruitment.
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Both of these are reported as "Active, not recruting" to ClinicalTrials.gov.
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Finally, enrolling participants depends on how difficult it is to find people
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who suffer from the condition of interest.
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