Benchmark Dose Software

Benchmark Dose Software (BMDS) Development History (1995-present)

This page summarizes BMDS development from its beginnings as a command-line program to highlights of the current software release. Many of the earlier entries appeared on the previous BMDS web site's "What's New" page. This page is an excellent reference if you want to know when a specific model was introduced or when specific features were changed or enhanced. 

However, if you are interested in BMDS's scientific history, and the discussions that contributed to its conceptual development, you can read the summary and links to BMDS peer reviews conducted from 2000-2008. 

On this page:

2015

February 23 - EPA is now distributing BMDS 2.6, a significant upgrade that includes several improvements to the nested models, parameter standard error reporting, parameter initialization for continuous models, file and path name handling, regional settings for the decimal separator, and other relatively minor issues. BMDS 2.6 also introduces a significant new feature: the ability for BMDS to automatically detect and, optionally, install software updates. This feature will ensure BMDS users have access to the latest version of the software with up-to-date fixes and enhancements.

This install package also includes an upgraded version (1.10) of the BMDS Wizard. BMDS Wizard v1.10 incorporates BMDS 2.6 reporting fixes and can also export Microsoft Word-formatted reports that employ the latest EPA-approved reporting format (as of September 2014). The Wizard can only export reports for continuous, dichotomous, and dichotomus-cancer models.

The BMDS 2.6 ReadMe file contains more details on this upgrade’s enhancements and fixes.

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2014

July 1 - EPA is distributing a new version of the BMDS continuous polynomial model that fixes an issue that resulted in incorrect parameter estimates for the first degree (linear) polynomial model when the beta1 (slope) parameter is restricted and variance is modeled as non-constant.


May 23 - EPA is now distributing BMDS 2.5, with an upgraded version (1.9) of the Excel-based BMDS Wizard. The BMDS Wizard has be upgraded to include a new template that allows users to run the MS_Combo model once all tumors have been run using the cancer template. Additionally, an issue with the cancer slope factor not exporting correctly has been resolved. A number of fixes have also been made to BMDS: (1) the “View Plot” functionality has been improved to make it easier to generate and edit a plot from a previously created .plt file; (2) the multistage, multistage cancer, and MS_Combo models now provide accurate results when non-integer input data are used and beta parameters are specified by the user; and (3) the power model now honors the direction of adversity specified by the user.

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2013

August 16 - EPA is now re-distributing BMDS 2.4, with an updated version (1.8) of the Excel-based BMDS Wizard. Version 1.8 of the Wizard has been modified so that it will (1) run correctly regardless of where BMDS is installed on a user's computer and (2) provide the user with the appropriate Multistage of Polynomial model choices given the number of dose groups in a dataset. The BMDS website has also been updated with (1) new instructions regarding how to download the source code for the software, and (2) information regarding the current versions of the individual model executable files.


April 19 - EPA is now distributing BMDS 2.4, which fixes issues related to data entry and running the MS_Combo and ten Berge models. Also, this version of BMDS provides preformatted BMDS Wizard templates. The BMDS Wizard is an Excel-based tool that streamlines data entry and option file creation, and implements logic to compare and analyze modeling results.

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2012

September 28 - EPA is now distributing BMDS 2.3.1, which simplifies how data validation errors for certain models are reported to the user and fixes interface issues reported to the BMDS development team since the release of Version 2.3.


September 12 - EPA is announcing an update of the Benchmark Dose Software (BMDS). The new BMDS Version 2.3 (Build 68) fixes several interface problems reported to the BMDS development team since the Version 2.2 release in late 2011. Most notably, BMDS 2.3 fixes a problem reported by users of Microsoft Office in Windows 7, in which clipboard errors would occasionally crash both BMDS and Microsoft Office. In addition, BMDS 2.3 now includes more flexible data input error-trapping functionality, enabling users to store comments, documentation, notations, etc. on dataset spreadsheets without triggering data validation errors. This change in functionality enables researchers to document their datasets as necessary within the BMDS environment. BMDS 2.3 contains no changes any of the BMDS dose-response models.


February 1 - EPA is making available source code files and executable files for the models in BMDS 2.2, as well as documentation for the new Multitumor model.

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2011

December 8 - EPA is now distributing BMDS 2.2 (Build 67), which includes minor modifications to the user interface.


September 6 - EPA is now distributing the final release of Version 2.2 (Build 66) of the Benchmark Dose Software (BMDS). Key enhancements in BMDS 2.2 (Build 66) include:
  • Multiple Tumor Analysis - BMDS 2.2 adds the capability to perform a combined analysis of multiple tumors. If the user is willing to assume that those tumors are independent and are well described by a multistage-cancer model, then the Multiple Tumor Analysis capability (accessed through the File/New or File/Open tool-bar choices) allows the user to estimate BMDs and BMDLs for the combined incidence of the tumors in question (i.e., BMDs and BMDLs for the likelihood of getting one or more of those tumors).
  • Trend Test for Dichotomous Data - Another major addition is the new capability to perform a trend test on dichotomous data sets. This is the first in a series of trend test to be added to BMDS (future versions will also include trend test for continuous and nested data). The trend testing feature can be found on the dataset screens, accessible once a dataset has been identified by the user as containing dichotomous response data. The test performed is the Cochran-Armitage trend test described by Haseman (1984).
  • The Dichotomous Hill model has been modified - Changes to the parameter initialization section of the Dichotomous Hill code have improved the convergence features of this model.
  • Automatic Transfer of Variable Name Changes to Other Option Files in a Session - When working within a session, variable name changes (e.g., for dose, sample size, response, mean, or standard deviation variables) made in one option file (i.e., for one model) can be "transferred" to other option files included in that session (i.e., those for other models). The user will be prompted to determine if variable name assignment changes made in one option file should be made in all other option files included in that session. Thus, users can change variable name assignments once in a session, without having to make those changes separately in every option file.
  • Default Column Headers for New Datasets - Note also that newly created dichotomous, continuous or nested model data files will start with default column headers, in a particular order, as appropriate for the type of data (e.g., Dose, N, and Effect for dichotomous datasets; Dose, N, Mean, and Std for summarized continuous datasets). The user may change those default headers, but will be warned that doing so may affect the running of BMDS-supplied sessions that look for those default names.

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2010

June 11 - EPA is now distributing the final release of Version 2.1.2 (Build 60) of the Benchmark Dose Software (BMDS). Key enhancements in BMDS 2.1.2 (Build 60) include:
  • Users can now use spaces in directory path and names associated with BMDS files, including data files.
  • The maximum number of characters allowed in directory path + file name has been increased to 256.
  • GnuPlot features have been added for enhanced plot viewing and editing.
  • Help file has been updated, and now includes a section describing the use of session and option file templates that are currently distributed with BMDS.
  • Polynomial and multistage models will now run, with warning messages, when the number of observations is less than the number of parameters being estimated.
  • Users can now specify the lower bound on the Weibull power parameter to be something other than 0 or 1.
  • The Toxicodiffusion model has been fixed so that it will run with all recent versions of R.

For details on these changes, go to the BMDS 2.1.2 Help menu option in the installed software. Also, the Readme.rtf file distributed with BMDS describes the improvements made in version 2.1.2 (Build 60), installation requirements, and known problems.

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2009

December 29 - EPA is announcing the availability of a new Time-To-Tumor Multistage Weibull Model ("MSW"). This model is run from a Windows command prompt window, data is submitted in a text file, and output is sent to a text file. The software was reviewed externally in late 2007 and revised and tested in 2008.


November 9 - EPA is now distributing Version 2.1.1 (Build 55) of the Benchmark Dose Software (BMDS). BMDS 2.1.1 (Build 55) contains a flexible new feature that allows users to export select BMDS summary report data and plots to Excel. It also contains a comprehensive set of sample session and model option files to assist users in running batch operations, and several improvements to the ten Berge model that were not available in version 2.1. The Readme.rtf file distributed with BMDS provides details on the improvements made in Version 2.1.1 (Build 55), installation requirements, and known problems.


July 30 - EPA is now distributing the final release of Version 2.1 (Build 52) of the Benchmark Dose Software (BMDS). BMDS 2.1 (Build 52) contains user interface enhancements as well as several additions/enhancements to the suite of models available for modeling dose-response data, including new features for the continuous exponential models and a new interface for the ten Berge concentration-time model. For details on the changes to the user interface, go to the BMDS 2.1 Help menu option in the installed software. The Readme.rtf file distributed with BMDS describes the improvements made in version 2.1 (Build 52), installation requirements, and known problems.

The exponential models contained in this version of BMDS have been developed in conjunction with the Netherlands' National Institute for Public Health and the Environment (RIVM) to be consistent with the exponential models contained in the RIVM's PROAST softwareExit. The USEPA and RIVM are working together to achieve consistency between the BMDS and PROAST software and methods.

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2008

September 30 - EPA is making version 2.1 of BMDS available at this time for public beta testing. Version 2.1 includes a beta (external peer review) version of a new time-dependent toxicodiffusion model for continuous outcomes (Zhu et al., 2005), incorporates graphical plots for the continuous exponential models and allows for the use of individual animal continuous response data. The BMDS toxicodiffusion model was developed by the USEPA National Center for Environmental Assessment (NCEA), through partnerships with the USEPA Neurotoxicology Division (NTD) and the University of South Florida, to characterize toxic effects (e.g., neurotoxicity) that potentially evolve along critical time points. It does this by:

  • modeling a dose-response along a time-course of repeated response measures; and
  • computing benchmark doses and their confidence limits along the time course.

Documentation for the toxicodiffusion model can also be downloaded. The documentation contains a full description of the model, input requirements, model run options and sample runs.

In addition, EPA is distributing an external review (beta) version of a concentration-time (CxT) model originally programmed by Wil ten Berge. The EPA ten Berge model implements an approach to evaluating the CxT relationships for effects associated with chemical exposures. The EPA's version 1.0 implementation of this model is being distributed along with associated documentation and comments on the model received from external peer reviewers. EPA plans to respond to external review comments and incorporate the ten Berge model into a future version of BMDS.

Finally, EPA has updated this website to offer new online and hands-on training opportunities. The online training tutorial has been updated for the 2.x versions of BMDS. A new web page has been added that details upcoming training opportinities.


July 10 - BMDS Version 2.0 final is now available. Released on July 10, 2008, it replaces BMDS 1.4.1c as the official BMDS software. BMDS 2.0 is a rewrite of the user interface and risk assessment modeling framework, with a markedly improved functionality and enhanced multi-model processing capabilities. It uses the same underlying source code for the models in BMDS 1.4.1 software, with minor corrections and some important additions. For details on the new user interface, go to the BMDS 2.0 Help menu option in the installed software. BMDS 2.0 also has a new set of quantal models with alternative background (i.e., background additive to dose) and asymptote (i.e., Hill model) parameters, as well as a Beta Exponential set of models.


January 9 - New online Benchmark Dose Software (BMDS) training is available on the EPA BMDS website. The training consists of five narrated sets of slides covering (1) Introduction to Benchmark Dose Modeling, (2) Modeling Dichotomous Data, (3) Modeling Dichotomous Cancer Data, (4) Modeling Continuous Data, and (5) Modeling Nested (e.g., Developmental) Data. This course is a narrated, online representation of EPA's 1-day Benchmark Dose Training course with examples using BMDS version 1.4.1c.

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2007

November 9 - BMDS version 1.4.1c is now available. This version updates dichotomous models that were already included on BMDS version 1.4.1b. The updates primarily improve the handling of parameter specifications, particularly in situations where the user may wish to specify the background parameter to be zero.


October 10 - BMDS 2.0 beta - Build 19 released on October 10, 2007 replaces the first BMDS 2.0 beta release of September 28, 2007 (Build 13). The new Build 19 has important changes and enhancements as a result of additional testing and user exposure and should be downloaded and used instead of Build 13. Enhancements include the ability to better run a number of the BMD models and also added flexibility and fixes for user interface features. Changes include the designation of the new Dichotomous models as Alternate Dichotomous to better reflect their production status. Please refer to the readme.txt file included with the software installation for more details on the BMDS 2.0 beta.


September 28 - BMDS Version 2.0 beta is now available for inspection and testing (NOTE: this is a beta test version, provided only for your examination and testing - BMDS 1.4.1b should be used for definitive risk assessment calculations). BMDS 2.0 beta employs a new graphical user interface and makes it easy to run a number of models for one data set and compare the results. BMDS 2.0 beta also has a new set of quantal models with alternative background parameters (i.e., background additive to dose). We welcome comments and suggestions on the functioning of the interface and its new features, and on the new models.


August 29 - BMDS Version 1.4.1b has been added to replace version 1.4.1. This version contains an update to the BMDS help file.


February 5 - Version 1.4.1 is now available. All models have been recompiled to improve speed, stability and compatibility with the latest Windows operating systems. Improvements have been made to the model output format for all models. A Multistage-Cancer model has been added which calculates and reports a cancer slope factor and plots the linear extrapolation from the BMDL to the background response estimate per EPA's 2005 cancer guidelines. Unlike the Multistage model, the Multistage Cancer model does not estimate added risk, nor does it allow beta coefficients to be unrestricted. The Quantal-Quadratic model was removed from Dichotomous model choices (note: the user can still run this model by specifying the power term of the Weibull model to be 2, but this model is not retained in the BMDS dichotomous model listings)

Issues in the continuous models that caused occasional errors in degrees of freedom assignments which impacted continuous model test results have been resolved. Acceptance criteria for Tests 2, 3 and 4 was changed from p>=0.05 to p>=0.1 and default risk type changed to "Std. Dev." for all continuous models to be consistent with EPA's draft BMD technical guidance (EPA, 2000). Issues with the Hill model have been fixed, including memory problems which were causing some operating systems to crash. Parameter standard error estimates and Chi-squared residual calculations in all the continuous models were checked and corrected if in error. Model A3 of the continuous model testing procedures has been modified so that it always uses the user-specified value for the parameter rho, including the constant-variance case where rho = 0. When rho = 0, model A3 is the same as model A1, and it is reported explicitly in the constant-variance runs. As a consequence, all model runs report the entire set of models (A1, A2, A3, R and the fitted model) and all four hypothesis tests.

Issues in the Nested models that caused occasional errors in degrees of freedom assignments have been resolved. Memory problems which were causing problems for some NCTR model runs have been fixed.

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2003

May 23 - Version 1.3.2 of BMDS is now available. Version 1.3.2 contains revised polynomial (poly.exe) and nested logistic (nlogist.exe) models that are compatible with Windows 2000. If you are using a Windows 98 or older operating system, you may need to update your msvcrt.dll driver. We suggest that you obtain the latest msvcrt.dll driver from microsoft and copy it to the c:\windows\system directory of your computer (you may have to exit Windows and do this in DOS mode).

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2002

November 13 - A new polynomial model (Version 2.2) is now available that fixes the previous incompatibility with Windows 2000.


January 22 - Version 1.3.1 of BMDS is now available. Version 1.3.1 contains a revised help manual and user interface, including a revision to the interface that allows the Multistage model to calculate BMD and BMDL values for very low (below E-5) benchmark response (BMR) levels.

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2001

March 22 - Version 1.3 of BMDS is now available.  This latest version of BMDS, version 1.3, contains new continuous Polynomial (v2.1), Power (v2.1) and Hill (v2.1) models, new dichotomous Multistage (v2.1), Weibull (v2.1) and Gamma (v2.2) models, and an improved user interface.  The new models are more compact and stable (will converge on BMD and BMDL solutions more often).  The user interface upgrades are described in the new help manual (PDF format) for version 1.3 and the readme.txt file that is distributed with the upgrade.


February 20 - Zip files containing source code for BMDS version 1.2.1 models are now available, along with instructions for compiling them. If you are a programmer and wish to revise the code, please do not distribute the revised code as EPA software.

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2000

October 25 - A new version of BMDS, version 1.2.1 is being distributed at this time.  This version contains new versions of the continuous Polynomial (version 2.1) and Hill (version 2.1) models.  If you do not want to completely reinstall BMDS, you can download the the new model executables and run them separately or under the BMDS version 1.2 interface.  These new versions of the polynomial and Hill models fix problems associated with running the model on Windows NT/2000 operating systems, provide improved model fit for certain unique data sets and improve upon the rate of convergence on a BMD and BMDL.


September 2 - A new user interface (BMDS0900.exe) was distributed to fix some problems with installation of BMDS on certain Windows 98 configurations.  If you successfully installed BMDS version 1.2 using a previous installation procedure you do not need this upgrade. This upgrade merely simplifies the installation process and corrects some problems that did not allow BMDS to install to certain computer hardware/software configurations. (This version of the software is no longer being made available as there are newer versions now available which fix problems that were being encountered on newer operating systems.)

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1995

EPA's National Center for Environmental Assessment (NCEA) Division in RTP, NC begins the development of the EPA's benchmark dose software (BMDS) application.

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