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@ -195,112 +195,112 @@ and
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\ref{SEC:Conclusion}
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\ref{SEC:Conclusion}
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respectively
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respectively
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\subsection{Market incentives and drug development}
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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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% %%%%%%%%% What do we know about drug development incentives?
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%
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\cite{dranove_DoesConsumer_2022} use the implementation of Medicare part D
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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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% 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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% the following 15 years.
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They find that when Medicare part D was implemented -- increasing senior
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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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% 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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% 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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% 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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% 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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% pharmaceuticals have a higher probability of failure compared to the less novel
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follow up development.
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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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% 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
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% % Acemoglu and Linn
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% - Market size in innovation
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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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% % - 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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% On the side of market analysis,
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\citeauthor{acemoglu_market_2004}
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% \citeauthor{acemoglu_market_2004}
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(\citeyear{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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% 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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% 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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% 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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% 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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% 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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% (as measured by demographic groups) leads to a 4\% increase in novel therapies.
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%
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% Gupta
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% % Gupta
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% - Inperfect intellectual property rights in the pharmaceutical industry
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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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% \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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% 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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% the primary patent has expired.
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She found that this delay in delivery is around 3 years.
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% She found that this delay in delivery is around 3 years.
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%
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% Agarwal and Gaule 2022
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% % Agarwal and Gaule 2022
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% - Retrospective on impact from COVID-19 pandemic
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% % - Retrospective on impact from COVID-19 pandemic
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% Not in this version
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% % Not in this version
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%
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\subsection{Understanding Failures in Drug Development}
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% \subsection{Understanding Failures in Drug Development}
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%
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% DISCUSS: Different types of failures
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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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% 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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% 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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% 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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% categories of failure apply to the individual trials as well as the entire
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drug development pipeline.
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% drug development pipeline.
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They generally fall into one of the following categories:
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% They generally fall into one of the following categories:
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\begin{itemize}
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% \begin{itemize}
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\item Scientific Failure: When there are issues regarding
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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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% safety and efficacy that must be addressed.
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The preeminient question is:
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% The preeminient question is:
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``Will the drug work for patients?''
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% ``Will the drug work for patients?''
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%E.Khm, Gupta, etc.
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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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% \item Strategic Failure: When the sponsors stop development because of
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profitability
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% profitability
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%Whether or not the drug will be profitiable, or align with
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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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% %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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% ``Will producing the drug be beneficial to the
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company in the long term?''
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% company in the long term?''
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%E.Khm, Gupta, GLP-1s, etc.
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% %E.Khm, Gupta, GLP-1s, etc.
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\item Operational concerns are answers to:
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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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% %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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% %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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% ``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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% finance, develop, produce, and market the drug?''
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\end{itemize}
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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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% 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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% combination of these factors.
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%
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%
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%USE MetaBio/CalBio GLP-1 story to illuistrate these different 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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% \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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% 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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% developing a GLP-1 based drug for diabetes or obesety before being shut down
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in .
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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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% 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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% 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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% 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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% At the time it was shut down, it faced a few challenges:
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\begin{itemize}
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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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% \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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% 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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% \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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% 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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% \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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% could not find other funding sources; an operational failure.
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\end{itemize}
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% \end{itemize}
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%
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The author states in his conclusion:
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% The author states in his conclusion:
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\begin{displayquote}
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% \begin{displayquote}
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Despite every possibility of success,
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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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% 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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% 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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% because proper corporate structure and adequate capital are always
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issues when attempting to survive predictable setbacks.
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% issues when attempting to survive predictable setbacks.
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\end{displayquote}
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% \end{displayquote}
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%
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From this we see that there was a cascade of issues leading to the failure to
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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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% develop this novel drug.
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%
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%
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% I don't think I need to include modelling enrollment here.
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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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% % 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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\end{document}
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will king
1 year ago