Dennis Sweitzer, Ph.D., Statistician

… past work, current ideas, and future directions….

Trial Management using Time-to-Event data
I'm glad to see people are starting to do some the of the Time-to-Event modeling & Simulation that I had done >10years ago. Cytel recently put this video on line.

Estimating the Analysis Date for Time-to-Event Study Endpoints -

Todd DeVries
 https://youtu.be/H4fwAC01iHE

The presentation of my work is here: (Annual meeting of the American Statistical Association, August 2006).
Modeling Multiphase Clinical Trials: Time to Completion, Study Management

… past work, current ideas, and future directions….

Simulation using Excel: A Clinical Study Application
This (hypothetical) spreadsheet simulation evaluates the impacts on timeline and budget of various combinations of high, medium, and low quality sites, and compares 2 options for performing an interim analysis: either after a fixed number of patients, or after a fixed length of time. Since enrollment rates are uncertain, the former option is more of a challenge for planning timelines, as the time of the interim analysis will vary, while the later risks having too few patients in the interim analysis.
Simulated costs for multiple scenarios are compared against a conventional point estimate of costs for the study, showing a high risk of going over budget because of uncertainty in screen failure and enrollment rates.




The next update will incorporate the 
SIPmath™ Modeler Tools for Excel v3.0. These tools should simplify some aspects of writing a simulation in Excel, but more importantly allow a simulation to be written that uses the results of other simulations as part of it's simulated universes, and publish it's results for use by other simulations and reports. They are found at:
(NB: these require later versions of MS Excel, and the code does not seem stable yet.)
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Introducing Tolstoy Targets: Motivation, Principles and Examples
Updated slides for my pet graphics project, Tolstoy Targets, including motivation, basic principles, and examples.
Next update will include applications to risk based study management.

https://sites.google.com/site/dennissweitzer/home/tolstoy-targets

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Modeling & Simulation in Managing Studies: Some Examples
http://www.slideshare.net/denswei/clinical-study-modeling-simulation
http://www.slideshare.net/denswei/clinical-study-modeling-simulation

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Randomization Metrics:
Jointly assessing predictability and efficiency loss in covariate adaptive randomization designs
 
A presentation given August 8, 2013 at the Joint Statistical Meetings in Montreal 

Randomization methods generally are designed to be both unpredictable and balanced between treatment allocations overall and within strata.  However, when planning studies, little consideration is given to measuring these characteristics, nor are they examined jointly, and published comparisons between methods often are not useful.

  In order to compare randomization performance, we simulated various covariate-adjusted randomization methods , and compared efficiency & unpredictability graphically and statistically using proposed metrics.

Randomization: Too important to gamble with

Randomization is a central part of Randomized Controlled Trials (RCTs) which are considered the 'gold standard' of clinical evidence. This talk is a basic introduction to the topic of randomization: It outlines how randomization is key to reducing various kinds of bias in a study; Explains several common randomization techniques; Proposes measurements of predictability and imbalance of a randomization method; And compares the performance of the methods in a series of simulations.

Summarized as a poster for the Society for Clinical Trials Annual meeting, May, 2013

Presented to the Delaware ASA monthly meeting in October, 2012

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Animated explanation of Tolstoy Targets:
 This simple & animated explanation starts from the very basics & includes examples from project management and chemical screening.
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Research Study in Pancreatic Cancer
THE EFFECTS OF PREDNISONE, MONTELUKAST, CETIRIZINE, RANITIDINE, POTASSIUM PHOSPHATE, MAGNESIUM, AND VERAPAMIL ON PANCREATIC ADENOCARCINOMA STAGE IV.

..is approved and ready to enroll.  This is a small proof of concept study to examine the benefits of this combination therapy in managing late stage pancreatic cancer symptoms.

For more details, see:  http://www.nashedspa.com/index.html
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January 2012 update:
Outline
•How to do Simulation in Excel
Notes on using Inverse Probability Functions
(For Verification, Validation, and Sensitivity)
• Some tools:  Excel Macros, Visual Basic Functions
• Examples from Clinical Trials
•Probability Management in SIPS, SLURPS, & DIST
Slides and spreadsheets at:
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My resume summarized as a word cloud:

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Haiku:

     Question (from someone on LinkedIn): "It is difficult for me to comprehend the difference between standard deviation and variance after having good amount of reading. Can you pl help me." 

    Answer (mine):

                                Variability
                        Standard Deviation Shows
                         Variance Calculates
   
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Targets, Traffic Lights, and Tolstoy

These 4 graphs plot project outcomes (for instance, Adverse Events, Efficacy goals, lab findings, schedule & budget).  Which projects are on target?  Which are in trouble?

These are splatter plots, a graphic I created to summarize outcomes of clinical studies by multiple criteria.  However, it is suitable for any project with multiple objectives, each of which can be categorized as Good/Uncertain/Bad on a scale of 0 to 10.  The defining metaphors are a threefold theme of Targets, Traffic Lights, and Tolstoy. 
Presented to the Delaware ASA monthly meeting in February 2011.

❊ Splatter Plots
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Quick & Simple Simulation using MS Excel

Excel is a general purpose spreadsheet which is widely used & understood, but rarely used by itself for simulations.  Industrial grade simulation in Excel requires add-in packages, while "casual" simulations are highly limited in scope (and could be described as "toy" simulations).

However, the Data Table function in MS Excel can be used to execute substantial simulations, without requiring cumbersome programming "tricks" or VBA coding to store iterated results.  The result is an arbitrarily large results table in which each row is one iteration of the simulation, and each column is a random variable generated in the simulation.

A small number of additional probability functions are easily programmed using VBA to make Excel a general purpose simulation package.  Because VBA is interpreted, use of VBA functions can greatly limit the speed of a simulation.  However, for simulations of modest size and complexity, the ease and familiarity of working in Excel, outweigh the disadvantages of speed.
Presented to the Delaware ASA monthly meeting in October, 2011
 is:
(1) A power point tutorial on implementing basic simulations in Excel
(2) An Excel spreadsheet template containing macros which ease writing simulations, some missing probability functions written in VBA, and examples.
(3) An Excel spreadsheet examples of specialized topics.
(3a)  Project management examples of using simulation in a CPM (Critical Path Method) context.

Quick & Simple Simulation using MS Excel
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Psephology, 2004

This is a tongue-in-cheek statistics talk that I gave sometime around the 2004 election cycle in the Bush vs Kerry match-up. In it, I outlined some quirky models for predicting election results, but also the approach used by Nate Silver of simulating state outcomes from models of polling data to predict the electoral college results. (This was long before Nate Silver was famous though).
Election Forecasting, 2004
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Sign of the Timings: Predicting Time of Completion in Multiphase Survival Clinical Trials

Studying maintenance of clinical effect typically requires clinical response for a minimum amount of time on treatment before randomization. If randomized, patients are then followed until treatment failure or withdrawal, and the trial halted after a pre-specified number of events. For ethical and cost reasons it is desirable to minimize the number of patients enrolled and randomized, and to predict the time of the last event under multiple scenarios.

We describe a data-driven stochastic simulation for two such trials in which: Each phase is modeled as a competing event process; Distributions of event times are derived from Kaplan-Meier survival curves from available data; Parameter uncertainty is modeled based on K-M survival estimates; Withdrawals and events occur at similar overall rates, though at different times; Predictions are updated as information is accrued.

Presented to: the Delaware ASA monthly meeting in September, 2006;  Annual meeting of the American Statistical Association, August 2006;
Modeling Multiphase Clinical Trials: Time to Completion, Study Management

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Quick and Dirty Simulation in Excel

I have often needed to do simple, flexible and quick ad hoc simulations while designing clinical trials (and other things).  Excel provides almost everything one needs to create an iterated simulation, missing only a few common random variables, a way to repeat the calculations using random variables, and a way to collect the results.  Commercial add-in products provide these features using custom programming, however I found one simple programming "trick" using iterated circular references to provide key functionality for iterated simulations.
Presented to the Delaware ASA monthly meeting in February 2010.