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@ -195,112 +195,112 @@ and
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\ref{SEC:Conclusion}
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respectively
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\subsection{Market incentives and drug development}
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%%%%%%%%% What do we know about drug development incentives?
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\cite{dranove_DoesConsumer_2022} use the implementation of Medicare part D
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to examine whether the production of novel or follow up drugs increases during
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the following 15 years.
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They find that when Medicare part D was implemented -- increasing senior
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citizens' ability to pay for drugs -- there was a (delayed) increase
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in drug development, with effects concentrated among compounds that were least
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innovative according to their classification of innovations.
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They suggest that this is due to financial risk management, as novel
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pharmaceuticals have a higher probability of failure compared to the less novel
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follow up development.
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This is what leads risk-adverse companies to prefer follow up development.
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% Acemoglu and Linn
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% - Market size in innovation
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% - Exogenous demographic trends has a large impact on the entry of non-generic drugs and new molecular entitites.
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On the side of market analysis,
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\citeauthor{acemoglu_market_2004}
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(\citeyear{acemoglu_market_2004})
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used exogenous deomographics changes to show that the
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entry of novel compounds is highly driven by the underlying aged population.
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They estimate that a 1\% increase in applicable demographics increase the
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entry of new drugs by 6\%, mostly concentrated among generics.
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Among non-generics, a 1\% increase in potential market size
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(as measured by demographic groups) leads to a 4\% increase in novel therapies.
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% Gupta
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% - Inperfect intellectual property rights in the pharmaceutical industry
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\cite{gupta_OneProduct_2020} discovered that uncertainty around which patents
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might apply to a novel drug causes a delay in the entry of generics after
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the primary patent has expired.
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She found that this delay in delivery is around 3 years.
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% Agarwal and Gaule 2022
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% - Retrospective on impact from COVID-19 pandemic
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% Not in this version
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\subsection{Understanding Failures in Drug Development}
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% DISCUSS: Different types of failures
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There are myriad of reasons that a drug candidate may not make it to market,
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regardless of it's novelty or known safety.
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In this work, I focus on the failure of individual clinical trials, but the
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categories of failure apply to the individual trials as well as the entire
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drug development pipeline.
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They generally fall into one of the following categories:
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\begin{itemize}
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\item Scientific Failure: When there are issues regarding
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safety and efficacy that must be addressed.
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The preeminient question is:
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``Will the drug work for patients?''
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%E.Khm, Gupta, etc.
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\item Strategic Failure: When the sponsors stop development because of
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profitability
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%Whether or not the drug will be profitiable, or align with
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%the drug developer's future Research \& Development directions i.e.
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``Will producing the drug be beneficial to the
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company in the long term?''
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%E.Khm, Gupta, GLP-1s, etc.
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\item Operational concerns are answers to:
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%Whether or not the developer can successfully conduct
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%operations to meet scientific or strategic goals, i.e.
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``What has prevented the the company from being able to
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finance, develop, produce, and market the drug?''
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\end{itemize}
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It is likely that a drug fails to complete the development cycle due to some
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combination of these factors.
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%USE MetaBio/CalBio GLP-1 story to illuistrate these different factors.
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\cite{flier_DrugDevelopment_2024} documents the case of MetaBio, a company
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he was involved in founding that was in the first stages of
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developing a GLP-1 based drug for diabetes or obesety before being shut down
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in .
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MetaBio was a wholy owned subsidiary of CalBio, a metabolic drug development
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firm, that recieved a \$30 million -- 5 year investment from Pfizer to
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persue development of GLP-1 based therapies.
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At the time it was shut down, it faced a few challenges:
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\begin{itemize}
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\item The compound had a short half life and they were seeking methods to
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improve it's effectiveness; a scientific failure.
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\item Pfizer imposed a requirement that it be delivered though a route
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other than injection (the known delivery mechanism); a strategic failure.
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\item When Pfizer pulled the plug, CalBio closed MetaBio because they
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could not find other funding sources; an operational failure.
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\end{itemize}
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The author states in his conclusion:
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\begin{displayquote}
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Despite every possibility of success,
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MetaBio went down because there were mistaken ideas about what was
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possible and what was not in the realm of metabolic therapeutics, and
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because proper corporate structure and adequate capital are always
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issues when attempting to survive predictable setbacks.
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\end{displayquote}
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From this we see that there was a cascade of issues leading to the failure to
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develop this novel drug.
|
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% I don't think I need to include modelling enrollment here.
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% If it is applicable, it can show up in those sections later.
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|
|
|
|
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% \subsection{Market incentives and drug development}
|
|
|
|
|
% %%%%%%%%% What do we know about drug development incentives?
|
|
|
|
|
%
|
|
|
|
|
% \cite{dranove_DoesConsumer_2022} use the implementation of Medicare part D
|
|
|
|
|
% to examine whether the production of novel or follow up drugs increases during
|
|
|
|
|
% the following 15 years.
|
|
|
|
|
% They find that when Medicare part D was implemented -- increasing senior
|
|
|
|
|
% citizens' ability to pay for drugs -- there was a (delayed) increase
|
|
|
|
|
% in drug development, with effects concentrated among compounds that were least
|
|
|
|
|
% innovative according to their classification of innovations.
|
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|
|
|
% They suggest that this is due to financial risk management, as novel
|
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|
|
|
% pharmaceuticals have a higher probability of failure compared to the less novel
|
|
|
|
|
% follow up development.
|
|
|
|
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% This is what leads risk-adverse companies to prefer follow up development.
|
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|
|
|
%
|
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|
|
|
%
|
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|
|
|
% % Acemoglu and Linn
|
|
|
|
|
% % - Market size in innovation
|
|
|
|
|
% % - Exogenous demographic trends has a large impact on the entry of non-generic drugs and new molecular entitites.
|
|
|
|
|
% On the side of market analysis,
|
|
|
|
|
% \citeauthor{acemoglu_market_2004}
|
|
|
|
|
% (\citeyear{acemoglu_market_2004})
|
|
|
|
|
% used exogenous deomographics changes to show that the
|
|
|
|
|
% entry of novel compounds is highly driven by the underlying aged population.
|
|
|
|
|
% They estimate that a 1\% increase in applicable demographics increase the
|
|
|
|
|
% entry of new drugs by 6\%, mostly concentrated among generics.
|
|
|
|
|
% Among non-generics, a 1\% increase in potential market size
|
|
|
|
|
% (as measured by demographic groups) leads to a 4\% increase in novel therapies.
|
|
|
|
|
%
|
|
|
|
|
% % Gupta
|
|
|
|
|
% % - Inperfect intellectual property rights in the pharmaceutical industry
|
|
|
|
|
% \cite{gupta_OneProduct_2020} discovered that uncertainty around which patents
|
|
|
|
|
% might apply to a novel drug causes a delay in the entry of generics after
|
|
|
|
|
% the primary patent has expired.
|
|
|
|
|
% She found that this delay in delivery is around 3 years.
|
|
|
|
|
%
|
|
|
|
|
% % Agarwal and Gaule 2022
|
|
|
|
|
% % - Retrospective on impact from COVID-19 pandemic
|
|
|
|
|
% % Not in this version
|
|
|
|
|
%
|
|
|
|
|
% \subsection{Understanding Failures in Drug Development}
|
|
|
|
|
%
|
|
|
|
|
% % DISCUSS: Different types of failures
|
|
|
|
|
% There are myriad of reasons that a drug candidate may not make it to market,
|
|
|
|
|
% regardless of it's novelty or known safety.
|
|
|
|
|
% In this work, I focus on the failure of individual clinical trials, but the
|
|
|
|
|
% categories of failure apply to the individual trials as well as the entire
|
|
|
|
|
% drug development pipeline.
|
|
|
|
|
% They generally fall into one of the following categories:
|
|
|
|
|
% \begin{itemize}
|
|
|
|
|
% \item Scientific Failure: When there are issues regarding
|
|
|
|
|
% safety and efficacy that must be addressed.
|
|
|
|
|
% The preeminient question is:
|
|
|
|
|
% ``Will the drug work for patients?''
|
|
|
|
|
% %E.Khm, Gupta, etc.
|
|
|
|
|
% \item Strategic Failure: When the sponsors stop development because of
|
|
|
|
|
% profitability
|
|
|
|
|
% %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.
|
|
|
|
|
%
|
|
|
|
|
%
|
|
|
|
|
% %USE 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:
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|
% \begin{displayquote}
|
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|
|
|
% Despite every possibility of success,
|
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|
|
|
% 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}
|
|
|
|
|
%
|
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|
|
|
% From this we see that there was a cascade of issues leading to the failure to
|
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|
|
|
% develop this novel drug.
|
|
|
|
|
%
|
|
|
|
|
%
|
|
|
|
|
% % I don't think I need to include modelling enrollment here.
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|
|
|
|
% % If it is applicable, it can show up in those sections later.
|
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|
|
|
%
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%
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\end{document}
|
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|
|
will king
1 year ago