From d6d67ad55e818a83d2576b34995f566dbd951a39 Mon Sep 17 00:00:00 2001 From: will king Date: Wed, 9 Oct 2024 00:37:13 -0700 Subject: [PATCH] added plans to structure the lit review --- Latex/Paper/sections/05_LitReview.tex | 60 +++++++++++++++++++++++++-- 1 file changed, 57 insertions(+), 3 deletions(-) diff --git a/Latex/Paper/sections/05_LitReview.tex b/Latex/Paper/sections/05_LitReview.tex index a692d3a..869e4ab 100644 --- a/Latex/Paper/sections/05_LitReview.tex +++ b/Latex/Paper/sections/05_LitReview.tex @@ -3,6 +3,56 @@ \begin{document} +% TODO: +%Need to distinguish that this isn't about drug development specifically, but +% more around clinical trials progress. +% Thoughts: +% - What types of failures do clinical trials have an why do clinical trials fail? +% - What is cited in termination reasons? +% - Discussion on different types of failures: +% 1. Failure to find safe and effective drug +% 2. Failure to collect enough information to determine 1 +% - recruiting +% - New information (other studies, changes in standards of care, etc) +% 3. Failure due to other operational/strategic concern. +% - Issues with PI/Sponsors +% - profitability expectations +% - Financial support +% Trials can fail due to issues in one of four categories +% - Scientific: The compound-indication combo is not sufficiently safe or efficatious +% - Strategic: The result from the trial won't meet the company's strategic needs. Profitability for the most part or entry into a drug category they don't want to invest in. +% - Operational: They can't bring resources to bear to achieve goal, e.g. site planning, PI's, delivering enough financial support, etc. +% - Tactical: The plans to discover if the approach is scientifically valid are insufficient. Study design, enrollment strategies, etc. + +% The literature examines many different aspects of these. +% strategic influences: elasticicity of innovation, demand pull, patents, etc +% Strategic vs scientific khmelniskaya, hwang. +% operational: Adam George Interview +% tactical: enrollment prediction. + + +% - Discuss how most studies are about clinical trials as part of the drug development pipeline. +% - Review what we know about causes for failure. +% - Things that correlate with failures. (adams) +% - Causes for failure (khmelnitskaya & hwang) +% - Then talk about studies on clinical trials themselves. +% - Interview with Adam George +% - Poor studies of enrollment prediction. +% - +% - Then talk about what drives approvals/clinical trial activity for drugs +% - Elasticity of innovation +% - No demand pull for novel drugs, but yes for derivatives +% - Population and Market size interact & drive development (jointly determined) +% - This doesn't apply to single trials though +% - +% - Sumarize +% - Thus when trying to study what affects clinical trials we must separate +% - Market & competition effects +% - Population effects +% - Multiple trial failure modes (safety & efficacy, Operational etc) +% - +% - + This paper sits within an intersection of health and industrial organization economics that is frequently studied. Encouraging a strong supply of novel and generic pharmaceuticals contributes @@ -19,7 +69,7 @@ which pharmaceutical companies operate. % - What causes high costs of drugs? % - High level synthesis of discussion regarding causes % - Academic and non-academic sources - +% Not particularly applicable %%%%%%%%%%%%%%%% What do we know about clinical trials? @@ -63,7 +113,7 @@ higher if those strategic terminatations were elimintated % Waring, Arrosmith, Leach, et al (2015) % - Atrition of drug candidates from four major pharma companies % - Looked at how phisicochemical properties affected clinical failure due to safety issues -%not in this version +% not Applicable in this version @@ -73,6 +123,7 @@ higher if those strategic terminatations were elimintated % Dranov, Garthwaite, and Hermosilla (2022) % - does the demand-pull theory of R&D explain novel compound development? % - no, it is biased towards follow-on drug R&D. +% TODO % Acemoglu and Linn % - Market size in innovation @@ -89,7 +140,10 @@ Among non-generics, a 1\% increase in potential market size % Gupta % - Inperfect intellectual property rights in the pharmaceutical industry -%\cite{GupaPhd2023} +\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 averages around 3 years. % Agarwal and Gaule 2022 % - Retrospective on impact from COVID-19 pandemic