diff --git a/Latex/Paper/sections/11_intro_and_lit.tex b/Latex/Paper/sections/11_intro_and_lit.tex index f3418ee..e39f6b9 100644 --- a/Latex/Paper/sections/11_intro_and_lit.tex +++ b/Latex/Paper/sections/11_intro_and_lit.tex @@ -195,112 +195,112 @@ and \ref{SEC:Conclusion} respectively -\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. -They suggest that this is due to financial risk management, as novel -pharmaceuticals have a higher probability of failure compared to the less novel -follow up development. -This is what leads risk-adverse companies to prefer follow up development. - - -% 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: -\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. - - -% I don't think I need to include modelling enrollment here. -% If it is applicable, it can show up in those sections later. - - +% \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. +% They suggest that this is due to financial risk management, as novel +% pharmaceuticals have a higher probability of failure compared to the less novel +% follow up development. +% This is what leads risk-adverse companies to prefer follow up development. +% +% +% % 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: +% \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. +% +% +% % I don't think I need to include modelling enrollment here. +% % If it is applicable, it can show up in those sections later. +% +% \end{document}