Wrote comments on things that should be improved

Paper/sections/08_PotentialImprovements.tex

@@ -4,13 +4,15 @@
 \begin{document}
 
 As noted above, there are various issues with the analysis as completed so far.
-Below I discuss various issues and ways to address them that I believe will improve the analysis.
+Below I discuss various issues and ways to address them that I believe 
+will improve the analysis.
 
 \subsection{Increasing number of observations}
 
-The most important step is to increase the number of observations available.
-Currently this requires matching trials to ICD-10 codes by hand.
-Improvements in Large-Language-Models may make this data more accessible, or
+The most important step is to increase the number of observations available,
+specifically the number of trials matched to ICD-10 codes with corresponding
+population estimates in the Global Burden of Disease Dataset.
+Improvements in Large Language Models may make this data more accessible, or
 the data may be available in a commercial dataset.
 
 
@@ -24,13 +26,11 @@ In most cases the trial sponsor reports the anticipated enrollment value
 while the trial is still recruiting and only updates the actual enrollment
 after the trial has ended.
 Some trials do publish an incremental record of their enrollment numbers, 
-but this is rare. 
-Due to the bayesian model used, it would be possible to 
-include a model of the missing data 
-\cite{mcelreath_statisticalrethinkingbayesian_2020}.
-which would
-allow me to estimate the direct effect of slow enrollment 
-on clinical trial termination rates.
+but this is not the norm. 
+It may be possible to impute the enrollment process if a suitible model
+can be created.
+% Due to the bayesian model used, this would be easy to incorporate
+% \cite{mcelreath_statisticalrethinkingbayesian_2020}.
 
 There has been substantial work on forecasting
 multi-site enrollment rates and durations by
@@ -51,24 +51,31 @@ multi-site enrollment rates and durations by
     avalos-pacheco_validationpredictiveanalyses_2023,
     }
 but choosing between the various single and multi-site models presented is 
-difficult without a dataset to validate the results on. 
-
-
-
-\subsection{Improving Population Estimates}
-
-The Global Burden of Disease dataset contains the best estimates of disease
-population sizes that I have found so far. 
-Unfortunately, for some conditions it can be relatively imprecise due to 
-its focus on providing data geared towards public health policy.
-For example, GBD contains categories for both
-drug resistant and drug suceptible tuberculosis, but maps those to the same 
-ICD-10 code.
-In contrast, there is no category for non-age related macular degeneration.
-Thus not every trial has a good match with the estimate of the population of
-interest.
-Finding a way to focus on trials that have good disease population estimates
-would improve the efficiency of the analysis.
+difficult without a dataset with which to validate the results.
+% In addition to needing a well calibrated model, I would require more trials,
+% specifically those that report their enrollment incrementally so 
+% that there is data on what happens when enrollment is slower than anticipated.
+% It may also be possible to estimate the probability that enrollment goals
+% have been met if data can be extracted that details planned observation times.
+% Of course, this is speculative at this point.
+%FIXTAG: Avoid speculation here.
+
+% \subsection{Improving Population Estimates}
+%
+% The Global Burden of Disease dataset contains the best estimates of disease
+% population sizes that I have found so far. 
+% Unfortunately, for some conditions it can be relatively imprecise due to 
+% its focus on providing data geared towards public health policy.
+% For example, GBD contains categories for both
+% drug resistant and drug suceptible tuberculosis, but maps those to the same 
+% ICD-10 code.
+% In contrast, there is no category for non-age related macular degeneration.
+% Thus not every trial has a good match with the estimate of the population of
+% interest.
+% Finding a way to focus on trials that have good disease population estimates
+% would improve the efficiency of the analysis.
+% %FIXTAG: What am I trying to say here. IHME is among the best data sources.
+% % How do I propose getting other data? Should probably just remove this.
 
 \subsection{Improving Measures of Market Conditions}
 
@@ -78,18 +85,24 @@ In addition to the fact that many diseases may be treated by non-pharmaceutical
 means (e.g. diet, physical therapy, medical devices, etc), 
 off-label prescription of pharmaceuticals is legal at the federal level 
 \cite{commissioner_understandingunapproveduse_2019}.
+%FIXTAG: Discuss how there isn't much data about off label prescription (I have a source)
 These two facts both complicate measuring competing treatments, 
 a key part of market conditions.
 One way to address non-pharmaceutical treatments is to concentrate on domains
 that are primarily treated by pharmaceuticals.
 Another way to address this would be to focus the analysis on just a few specific
 diseases, for which a history of treatment options can be compiled.
+%FIXTAG: Get rid of 'another', doesn't match context
 This second approach may also allow the researcher to distinguish the direction
 of causality between population size and number of drugs on the market; 
+%FIXTAG: join better to prior sentence
 for example, drugs to treat a chronic, non-fatal disease will probably not 
 affect the market size much in the short to medium term.
-This allows the effect of market conditions to be isolated from
-the effects of the population.
+This would require identifying diseases that are prime candidates and then
+trials and drugs associated with those diseases.
+% This allows the effect of market conditions to be isolated from
+% the effects of the population.
+% %FIXTAG: I am already proposing these as fixes
 
 % Alternative approaches 
 % - diseases with constant kill rates? population effect should be relatively constant?

Paper/sections/09_Conclusion.tex

@@ -5,35 +5,39 @@
 Identifying commercial impediments to successfully completing 
 clinical trials in otherwise capable pharmaceuticals will hopefully 
 lead to a more robust and competitive pharmaceutical market.
+%FIXTAG: too much "hopefully"
 Although the current state of this research is insufficient to draw robust
 conclusions, these early results suggest that delaying the close of 
-enrollment periods reduces the probability of termination of a trial.
+enrollment period reduces the probability of termination of a trial.
+%FIXTAG: OK for now but I think there might be a better way to handle this for now
 
-The successful completion of Phase III clinical trials is crucial for 
-bringing new treatments to market.  
-This research provides insights into how enrollment management 
-impacts trial outcomes.
-While the preliminary results suggest that delaying the close of enrollment 
-periods may reduce termination probability, the analysis 
-reveals significant variation across disease categories and highlights 
-important methodological challenges. 
+% The successful completion of Phase III clinical trials is crucial for 
+% bringing new treatments to market.  
+%FIXTAG: needs to be earlier
 The primary limitation that must be addressed before drawing a strong conclusion
 is that of insufficient data. 
+%FIXTAG: This needs rewritten
 This takes two forms.
+%FIXTAG: needs better transition 
 The first is the small sample size. 
 To overcome this requires an improved data matching 
 approach and a revised data scraper.
+%FIXTAG: active voice: this can be overcome by...
 The second is creating a model of enrollment that can be used to address
 the causal identification issue from the joint determination of
 enrollment statuses and elapsed durations of trials.
+%FIXTAG: sentence is too complicated
 
 Despite these limitations, this work establishes a framework for analyzing 
 operational versus strategic factors in clinical trial completion. 
+%FIXTAG: analyzing replaced with "separating causal effects"
 The approach developed here can be extended with additional data to 
 provide more definitive guidance on enrollment management strategies. 
+%FIXTAG: the approach here + additional data can provide
+%FIXTAG: tie to next sentence better
 Further research in this direction could help reduce operational 
 barriers to trial completion or estimating the impact policies may have through
-operational channels.
+operational channels.%FIXTAG: clauses don't match. first clause needs tightened.
 Ultimately this work will hopefully support more efficient drug 
-development and increased market competition.
+development and increased market competition. %FIXTAG: wishy-washy and duplicative.
 \end{document}