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Developing new, effective pharmaceutical compounds is a fundamentally difficult task.
Starting with challenges identifying promising treatment targets and potential compounds, to ensuring the drug can be properly delivered within the body, the scientific work that needs to go well is massive.
The regulatory and market conditions in which they exist add to this difficulty. 
For example, regulations are designed to reduce the number of drugs released to market
with significan issues, such as in the case of VIOXX \cite{krumholz_whathavewe_2007}
or the Perdue Pharma scandal \cite{officepublicaffairsjusticedepartment_2020}.
These regulations, such as clinical trial standards \todo{add citation to clinical trials here}, 
increase the costs of developing new drugs, adding to the business conserns already present, including 
competitors already in the market or close to entering and the overall demand to address a given condition.

This work is the first that endeavors to separate the causal effect
of an operational concern (participant enrollment) from that of strategic 
concerns (market size and competitors in the market) 
on individual clinical trials. 

%begin discussing failures
%I am thinking I'll discuss marketing and operational failures
%I somehow need to step away from the drug development framing and soften it to ... what? drug investigation?

Understanding both why and how the development of drugs fail -- for both 
novel and derivative pharmaceuticals -- is key to ensuring that both innovation
and availability are maximized.
There are myriad of reasons that a drug candidate may not make it to market, 
regardless of it's novelty or known safety.
These reasons for failure generally fall into one of the following categories:
\begin{itemize}
    \item Scientific concerns arise while asking the question
        %Whether or not the drug is sufficiently safe and 
        %efficatious for the disease it is trying to treat i.e. 
        ``Will the drug work for patients?''
        %E.Khm, Gupta, etc.
    \item Strategic concerns ask: 
        %Whether or not the drug will be profitiable, or align with
        %the drug developer's future Research \& Development directions i.e.
        ``Will producing the drug be beneficial to the 
        company in the long term?''
        %E.Khm, Gupta, GLP-1s, etc.
    \item Operational concerns are answers to: 
        %Whether or not the developer can successfully conduct
        %operations to meet scientific or strategic goals, i.e. 
        ``What has prevented the the company from being able to 
        finance, develop, produce, and market the drug?''
\end{itemize}
It is likely that a drug fails to complete the development cycle due to some
combination of these factors. 

%MetaBio/CalBio GLP-1 story to illuistrate these different factors.
\cite{flier_DrugDevelopment_2024} documents the case of MetaBio, a company
he was involved in founding that was in the first stages of
developing a GLP-1 based drug for diabetes or obesety before being shut down
in . 
MetaBio was a wholy owned subsidiary of CalBio, a metabolic drug development 
firm, that recieved a \$30 million -- 5 year investment from Pfizer to 
persue development of GLP-1 based therapies. 
At the time it was shut down, it faced a few challenges:
\begin{itemize}
    \item The compound had a short half life and they were seeking methods to 
        improve it's effectiveness; a scientific failure.
    \item Pfizer imposed a requirement that it be delivered though a route
        other than injection (the known delivery mechanism); a strategic failure. 
    \item When Pfizer pulled the plug, CalBio closed MetaBio because they 
        could not find other funding sources; an operational failure.
\end{itemize}

The author states in his conclusion:
\begin{displayquote}
    Despite every possibility of success, 
    MetaBio went down because there were mistaken ideas about what was 
    possible and what was not in the realm of metabolic therapeutics, and 
    because proper corporate structure and adequate capital are always 
    issues when attempting to survive predictable setbacks.
\end{displayquote} 

From this we see that there was a cascade of issues leading to the failure to 
develop this novel drug. 
Knowing how to separate 



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