Provided by: simrisc_15.03.00-2_amd64 
NAME
simriscparams - The description of the configuration files
DESCRIPTION
This page describes the organization of the simrisc configuration files. These files are
formatted like standard unix configuration files. Lines are interpreted after removing
initial white-space (blanks and tabs) and after removing all characters from lines
starting at the first # character: this is considered comment and is ignored. If a line
(not containing a # character) ends in a backslash (\), then the next line (initial
white-space removed) is appended to the current line.
Note that all parameter identifiers are interpreted case sensitively. E.g., Costs: is a
different parameter than costs:. The numeric values used in this man-page are for
illustration purpose only. Some restrictions apply though: standard deviations cannot be
negative; proportions and probabilities must lie in the range 0..1; multiple probabilities
(like the ones used for breast densities) must add up to 1; etc. If restrictions apply
then they are mentioned at the various parameter descriptions below.
DEFAULT CONFIGURATION FILE
The configuration file provided in the simrisc distribution is
/usr/share/doc/simrisc/simrisc.gz.
Usually this file is unzipped by the user to the user’s ~/.config directory:
gunzip < /usr/share/doc/simrisc/simrisc.gz > ~/.config/
whereafter ~/.config/simrisc can be edited to contain local modifications.
Various parameters specify probability distributions. Usually the Normal distribution is
specified. The program also recognizes the LogNormal and Uniform distributions, and uses
the Beta distribution when handling parameter variations of the beta parameter used for
lung cancer simulations (note that the similarity of the names beta (the parameter) and
Beta (the distribution) is sheer accidentally).
Parameter specifications start with keywords, followed by a colon. All keywords are
covered below. The format of the specifications is fixed, but empty lines and white space
may be used to improve the specifications’ readabilities.
Parameter specifications starting with uppercase letters (like Scenario:) specify
(sub)sections and contain no additional specifications. Specifications starting with
lowercase letters (like ageGroup:) are followed by actual parameter values.
The configuration file must define all parameters of all configuration sections, but
configuration parameters can be modified using a separate analysis file or they can be
modified by command-line parameters.
Changes introduced in version 15.01.00
o
Section `Scenario:’
This section starts with a line containing Scenario: and it defines some general
parameters that are used during the simulation process. The default configuration file
contains the following specifications:
o spread: false
when specified as true parameter spreading is used;
o iterations: 1
the (positive) number of iterations used in a simulation loop;
o generator: fixed
in addition to fixed the modes random and increasing are available.
This parameter specificies the way simrisc’s random number generators are
initialized. When mode fixed is used the random number generators are initialized
with seed’s value; mode random results in the random number generators being
initialized by randomly selected seeds and seed (below) is not used; mode
increasing results in incrementing the seeds of the random number generators by a
fixed increment at each iteration;
o seed: 1
the (positive) value to seed the random number generator with. This parameter is
ignored when generator: random was specified;
o cases: 1000
the (positive) number of cases being simulated;
o death: ...
the death: parameter may either be followed by the path to a file (if its initial
character is a tilde (~) it is replaced by the user’s home directory; if it’s a
plus (+) it is replaced by the base directory (specified with the --base option,
see the simrisc(1) man-page)), or it must be followed by 101 cumulative death
proportions, where each line starts with <nr>:, where <nr> is the next order number
to read. The default configuration file specifies:
death:
1: .00000 .00000 .00000 .00000 .00000 .00000 .00000 .00000 .00000 .00000
11: .00000 .00000 .00000 .00000 .00000 .00000 .00000 .00000 .00000 .00000
21: .00000 .00014 .00028 .00042 .00056 .00070 .00106 .00142 .00178 .00214
31: .00250 .00382 .00514 .00646 .00778 .00910 .01118 .01326 .01534 .01742
41: .01950 .02312 .02674 .03036 .03398 .03760 .04414 .05068 .05722 .06376
51: .07030 .07776 .08522 .09268 .10014 .10760 .11564 .12368 .13172 .13976
61: .14780 .15718 .16656 .17594 .18532 .19470 .20658 .21846 .23034 .24222
71: .25410 .27560 .29710 .31860 .34010 .36160 .39368 .42576 .45784 .48992
81: .52200 .56240 .60280 .64320 .68360 .72400 .75826 .79252 .82678 .86104
91: .89530 .90962 .92394 .93826 .95258 .96690 .97104 .97518 .97932 .98346
101: .98760
which are the 101 cumulative death proportions used for breast cancer simulations.
If the 101 cumulative death proportions aee available in, e.g., the user’s .config/
directory as the file cumdeath then the specification could have been:
death: ~/.config/cumdeath
which might be convenient when using different values in Analysis: specifications
(see section ANALYSES in the simrisc(1) man-page).
Section `Costs:’
This section starts with a line containing Costs: and it defines several parameters used
for cost-calculations. Modality-specific cost parameters are specified at Section
Modalities: (see below). The default configuration file specifies:
o biop: 176
the (positive) cost of performing a biopsy;
o diameters: 0: 6438 20: 7128 50: 7701
pairs of diameter: cost values specifying the treatment cost starting at the
specified tumor diameter, up to the next pair’s diameter (if specified) or all
diameters starting at the diameter specified at the last pair. The first diameter
must be 0. The second value of each pair specifies the (non-negative) treatment
costs for that age-group.
o Discount:
the costs discount proportion starting at some age. This line is followed by two
additional lines: the line discount: contains two values specifying, respectively,
the discount proportions for breast- and lung-cancer simulations; the line age:
specifies the discount’s starting age (for both simulation types):
Discount: # breast lung
proportion: 0 .04
age: 50
Section `BreastDensities:’
This section starts with a line containing BreastDensities: which are used with
breast-cancer simulations. It defines breast density values for various age groups,
covering ages 0 through the maximum age for simulated cases. The default configuration
file contains the following specifications:
# bi-rad: a b c d
ageGroup: 0 - 40 0.05 0.30 0.48 0.17
ageGroup: 40 - 50 0.06 0.34 0.47 0.13
ageGroup: 50 - 60 0.08 0.50 0.37 0.05
ageGroup: 60 - 70 0.15 0.53 0.29 0.03
ageGroup: 70 - * 0.18 0.54 0.26 0.02
Age groups are half-open ranges: starting at their first ages, and end at (not including)
their second ages. The first ages of subsequent age groups must be equal to the second
ages of their previous age groups. For the last age group the specification * can be used,
indicating that all ages at or above the last age group’s begin age are handled by that
group.
For each age group the probabilities of the four bi-rad classifications must sum to 1.0.
Section Modalities:
This section starts with a line containing Modalities: and it specifies cancer-scanning
modalities. Currently three modalities are supported: Mammo, Tomo, MRI (which are used
with breast-cancer simulations), and CT (which is used with lung-cancer simulations).
Some modalities specify age groups, which are (like the age ranges used for
breastDensities) half-open ranges: they start at their first ages, and end at (not
including) their second-ages, while subsequent age ranges must connect. Also, the last age
group may use the end-age specification *.
The default configuration file contains (below the line Modalities:) the following
specifications (if modalities aren’t used their specifications are optional):
o CT:
The CT modality is used when performing lung cancer simulations. The screening
costs are used instead of the value configured at the Costs: biop: specification.
The diagnosis: costs specifies the costs of performing a CT-scan. The M0 and M1
values specify the costs when, respectively, no metastatis or a matastasis has been
detected.
The radiation dose of CT scans is configured at the CT: dose: specification. The
sensitivity depends on the tumor diameter. For tumor sizes between 3 and 5 mm. the
sensitivity is computed using the formula (.5 * diameter - 1..5) * 100 (e.g., 50%
for tumors of 4 mm.)
The default configuration file contains the following CT specifications:
CT:
# screening diagnosis M0 M1 (M0, M1: Table S3)
costs: 176 1908 37909 56556
dose: 1
# diam. value (must be integral 0..100 or -1)
sensitivity: 0 - 3: 0
sensitivity: 3 - 5: -1 # formula: (.5 * diam - 1.5) * 100
sensitivity: 5 - *: 100
# mean stddev dist
specificity: .992 .076 Normal
o Mammo:
For the Mammo modality the costs, radiation doses and m: parameter specifications
per bi-rad category, specificity probabilities for age groups, the parameters of
the beta-function, and the systematic error probability must be specified.
The Mammo sensitivity is computed using the beta-function published by Isheden and
Humphreys (2017, Statistical Methods in Medical Research, 28(3), 681-702). From a
randomly generated probability and the case’s age the case’s bi-rad category is
determined and that category is then used to select the m-parameter that is used in
the beta-function.
The default configuration file contains the following Mammo specifications:
Mammo:
costs: 64
# bi-rad: a b c d
dose: 3 3 3 3
m: .136 .136 .136 .136
# ageGroup
specificity: 0 - 40: .961 40 - *: .965
# 1 2 3 4
beta: -4.38 .49 -1.34 -7.18
systematicError: 0.1
o Tomo:
For the Tomo modality the costs, radiation doses per bi-rad category, sensitivity
probabilities per bi-rad category, and specificity probabilities for age groups
must be specified.
The default configuration file contains the following Tomo specifications:
Tomo:
costs: 64
# bi-rad: a b c d
dose: 3 3 3 3
sensitivity: .87 .84 .73 .65
# ageGroup
specificity: 0 - 40: .961 40 - *: .965
o MRI:
For the MRI modality the costs, and the sensitivity and specificity probabilities
must be specified.
The default configuration file contains (below the line MRI:) the following
specifications:
costs: 280
# proportion
sensitivity: .94
specificity: .95
Section `Screening:’
This section starts with a line containing Screening: and it defines the ages at which
screenings are performed, the used screening modality/modalities for each of the used
screening ages, and contains the the screenings attendance probability. If no screening
rounds should be used then specify a single round-specification line:
round: none
Otherwise, each screening round is defined by the keyword round: followed by an age, which
in turn is followed by a list of at least one space delimited modality specification.
Currently Mammo, Tomo, MRI and CT are available. Mammo, Tomo, and MRI can be specified
when performing breast-cancer simulations, CT can be specified when performing lung-cancer
simulations. The default configuration file contains the Screening: specifications also
used in versions before 15.00.00:
round: 50 Mammo
round: 52 Mammo
round: 54 Mammo
round: 56 Mammo
round: 58 Mammo
round: 60 Mammo
round: 62 Mammo
round: 64 Mammo
round: 66 Mammo
round: 68 Mammo
round: 70 Mammo
round: 72 Mammo
round: 74 Mammo
For lung cancer simulations the CT modality must be specified, either in an analysis
specification or by altering the configuration file. E.g.,
Screening:
round: 50 CT
round: 52 CT
round: 54 CT
round: 56 CT
round: 58 CT
round: 60 CT
round: 62 CT
round: 64 CT
round: 66 CT
round: 68 CT
round: 70 CT
round: 72 CT
round: 74 CT
# probability:
attendanceRate: .8
Section `Tumor:’
This section starts with a line containing Tumor: and it defines the parameters specifying
tumor characteristics. Several of the parameters in this section can be varied by
specifying spread: true in the section Scenario:, in which case statistical variations are
applied to these parameters.
Supported distributions are Normal, Uniform, LogNormal, and (for the lung-cancer Beir7
parameters) the Beta distribution . If value is the specified value parameter value, and
spread the specified spread parameter then the values that are actually used during the
simulations are:
o when using the Normal distribution N(mean, stddev):
N(value, spread)
o when using the Uniform distribution U(begin, end):
U(value - spread / 2, value + spread / 2)
o when using the LogNormal distribution L(mean, stddev):
L(value, spread)
o the Beta distribution is used when lung cancer simulations are performed. For male
cases the 95% confidence intervals for the beta parameters ranges from .15 to .70,
for female cases it ranges from .94 to 2.10, and values drawn from these
distributions are used when spread: true has been specified (see also section BETA
DISTRIBUTIONS).
The spread parameters may not be negative. If spread values are configured then their
distributions must also be specified. If spread is not specified, then the value
parameter won’t vary if spread: true is specified in the Scenario section. The same holds
true for the Beta distribution: if no spreading should be applied, even though spread:
true was specified, then the Beta distribution’s specificatins should be omitted.
The Tumor: section has four subsections: Beir7:, Growth, Incidence:, Survival:, and S3:.
They contain the following parameter specifications:
Beir7:
BEIR (tumor induction) parameters: only tumor induction type 7 (i.e., beir7) is used. The
default configuration file contains specifications for breast cancer simulations and for
male and female lung cancer simulations:
# eta beta spread dist.
breast: -2.0 0.51 0.32 Normal
# Beta-distribution parameters:
# LC: eta beta dist constant factor aParam bParam
male: -1.4 .32 Beta .234091 1.72727 2.664237 5.184883
female: -1.4 1.40 Beta .744828 .818966 3.366115 4.813548
If spread: true is specified then the actually used beta parameters are drawn from their
respective distributions.
See also National Research Council. 2006. Health Risks from Exposure to Low Levels of
Ionizing Radiation: BEIR VII Phase 2. Washington, DC: The National Academies Press
(https://doi.org/10.17226/11340).
Growth:
Tumor growth specifications consist of three elements: start diameters, self-detect
parameterss and doubling time specifications.
The start parameters define the start diameter of emerging tumors used with respectively,
breast and lung cancer simulations . The default configuration file specifies
# breast lung
start: 5 3
The default configuration file contains these specifications of the self-detect parameters
for breast and lung cancer simulations:
#selfDetect: # stdev mean spread dist
breast: .70 2.92 .084 Normal
lung: .014 3.037 .61 Normal
Four parameters are used to determine the diameter at which self-detection is possible.
These parameters are:
o the standard deviation (stdev) used by the lognormal distribution to compute the
diameter at which self-detection occurs. This parameter is required and cannot be
negative;
o the mean (see below) used by the lognormal distribution. This parameter is required
and cannot be negative. Its value will vary using the following two parameters if
spread: true was specified;
o the spread (standard deviation) used by the distribution that is used to vary the
mean if spread: true was specified. It can be omitted in which case the mean won’t
vary;
o the distribution used to vary the mean. If the previous parameter is omitted then
this parameter must also be omitted.
The actually used self-detect diameter is computed using:
diameter = L(mean, stdev)
Finally, the Growth: subsection also defines tumor doubling times for various age groups
when using breast cancer simulations and for all ages when using lung cancer simulations.
Doubling times are computed like the self-detect diameters, i.e., using lognormal
distributions. Thus, for each age group and for the lung cancer simulation four parameters
are specified (of which the final two are optional): the standard deviation of the
lognormal distribution, the mean value of the lognormal distribution, and the spread and
name of the distribution that is used when spread: true was specified.
The age groups (used with breast cancer simulations) must cover ages 0 through the maximum
age for simulated cases, and are specified as described at section BreastDensities:. The
default configuration file contains the following specifications:
DoublingTime:
# stdev mean spread dist.
ageGroup: 1 - 50 .61 4.38 .43 Normal
ageGroup: 50 - 70 .26 5.06 .17 Normal
ageGroup: 70 - * .45 5.24 .23 Normal
# all ages stdev mean spread dist.
lung: .21 4.59 .74 Normal
Incidence:
For breast cancer simulations three carrier types are supported: Normal, BRCA1 and BRCA2.
Each having a probability of occurrence. The probabilities of these carriers must add to
1. In the default configuration file BRCA1 and BRCA2 are specified, but their probabilties
are set to 0, in which case their specifications can also be removed from configuration
files.
Each carrier is identified by name (i.e., when performing breast cancer simulations
Breast:, BRCA1:, and BRCA2; when performing lung cancer simulations: Male: and Female:)
followed by their parameter specifications:
o for breast cancer simulations: the probability that the carrier is observed;
o the lifetime risk: three parameters specifying a probability;
o the mean age: three parameters specifying the mean age,;
o the standard deviation used when computing the risk of getting a tumor. As this
standard deviation is used in the denominator of expressions it must be larger than
zero.
The lifetime risk, mean age and standard deviation parameters may optionally be followed
by the standard deviation (spread) and distribution used to vary the probability when
spread: true is specified;
The default configuration file contains these specifications:
Incidence:
Male:
# value spread distr.
lifetimeRisk: .22 .005 Normal
meanAge: 72.48 1.08 Normal
stdDev: 9.28 1.62 Normal
Female:
# value spread distr.
lifetimeRisk: .20 .004 Normal
meanAge: 69.62 1.49 Normal
stdDev: 9.73 1.83 Normal
Breast:
probability: 1
# value spread distr.
lifetimeRisk: .226 .0053 Normal
meanAge: 72.9 .552 Normal
stdDev: 21.1
BRCA1:
probability: 0
# value spread distr.
lifetimeRisk: .96
meanAge: 53.9
stdDev: 16.51
BRCA2:
probability: 0
# value spread distr.
lifetimeRisk: .96
meanAge: 53.9
stdDev: 16.51
Survival:
For breast cancer simulations four types of survival parameters must be specified. Each
type (a..d) specifies a mean, and (optionally) a spread and distribution (which are used
when spread: true has been specified). The default configuration file specifies:
Survival:
# value spread dist:
type: a .00004475 .000004392 Normal
type: b 1.85867 .0420 Normal
type: c -.271 .0101 Normal
type: d 2.0167 .0366 Normal
For lung cancer simulations table S4 is used to determine the a..d parameters. Table S4
contains four categories (lung0..lung3) defining these a..d parameters, where (for a known
cancer’s diameter) the category is randomly determined using table S3 (see below).
Table S4 is appended to the breast cancer specifications. The default configuration file
contains the following specifications of table S4:
# table S4: 4 columns per a..d parameter
# lungX: X is table S4’s column index
lung0: a .00143 .00095 Normal
lung0: b 1.84559 .33748 Normal
lung0: c -.22794 .07823 Normal
lung0: d 1.06799 .16226 Normal
lung1: a .01530 .00381 Normal
lung1: b 1.69434 .10979 Normal
lung1: c -.19358 .02105 Normal
lung1: d .66690 .03869 Normal
lung2: a .78600 .29815 Normal
lung2: b .69791 .05425 Normal
lung2: c .0 .0 Normal
lung2: d .0 .0 Normal
lung3: a 1.25148 .32305 Normal
lung3: b .77852 .34149 Normal
lung3: c .0 .0 Normal
lung3: d .0 .0 Normal
S3:
With lung cancer specifications tables S3 and S4 are used to determine the survival
parameters. The tumor’s diameter determines the row of table S3, and then its column is
randomly determined using the probabilities listed in S3’s rows. For each row the
probabilities must sum to 1. Once the S3 column has been determined the column index which
of the lungX: specifications is used. The row and column indices are 0-based. E.g., if a
tumor diameter is 24, then row 2 (diameter <= 30) is selected. Then, if the random value
is .630, column 1 is used (column N1-3,M0). Whenever a tumor is present these pairs of
indices are reported in the comma-separated data file in the column marked as TNM, using
an entry like 2,1.
The default configuration file contains the following table S3:
S3:
# diameter (mm)
# T-row <= N0,M0 N1-3,M0 N1-3,M1a-b N0-3M1c
prob: 10: .756 .157 .048 .039 # T1a,b
prob: 20: .703 .197 .055 .045 # T1b
prob: 30: .559 .267 .095 .078 # T1c
prob: 50: .345 .351 .167 .137 # T2a,b
prob: 70: .196 .408 .218 .178 # T3
prob: *: .187 .347 .256 .210 # T4
(cf. https://www.sciencedirect.com/science/article/pii/S2667005421000491 and Table 1 of
its appendix: https://ars.els-cdn.com/content/image/1-s2.0-S2667005421000491-mmc1.pdf)
bc:
When performing breast cancer simulations TNM indices (cf. the description of the S3
table) are also determined. Here the second TNM value is always 0, and the first TNM value
is, as with table S3, determined by the tumor’s diameter. The default configuration file
contains the following bc: specification:
# BC TNM categories thru (<=) diameters (mm):
bc: 20 50 *
# TNM: T1 T2 T3
(cf.
https://www.cancerresearchuk.org/about-cancer/breast-cancer/stages-types-grades/tnm-staging).
(see also option --tnm).
BETA DISTRIBUTIONS
Values generated from Beta distributions range between 0 and 1 (cf.
https://en.wikipedia.org/wiki/Beta_distribution). The Beta distribution is computed using
two Gamma distributions (cf.
https://www.fmrib.ox.ac.uk/datasets/techrep/tr03tb1/tr03tb1/node24.html,
https://stats.stackexchange.com/questions/502146/how-does-numpy-generate-samples-from-a-beta-distribution):
gamma1 = Gamma(aParam, 1)
Beta(aParam, bParam) = gamma1 / (gamma1 + Gamma(bParam, 1))
When using lung cancer simulations the 95% confidence interval (CI) for male cases ranges
from .15 to .70, with a mean value of .32, and for women ranging from .94 to 2.10 with a
mean value of 1.40.
The male and female CI ranges are transformed to .025 to .975 ranges using linear
transformations. To transform values x from the male range to the .025 to .975 range the
transformation y = 1.72727 * x - .234091 is used, and to transform back the transformation
(y + .234091) / 1.72727 is used. For the female CI the transformations are y = .818966 *
x - .744828 and (y + .744828) / .818966.
The aParam and bParam values are determined by first generating 1000 values so that their
CI span the range 0.025 to .975, with a mean value of 0.318635 (for male cases) and
0.401724 (for female cases). Next the parameters of the corresponding beta distribution
were estimated using maximum likelihood fitting, resulting in aParam = 2.664237 and bParam
= 5.184883 for the distribution used with male lungcancer simulations, and aParam =
3.366115 and bParam = 4.813548 for the distribution used with female lungcancer
simulations.
The default configuration file shows these values at the Beir7 beta parameters.
PARAMETER RESPECIFICATION
Parameters can be respecified by defining a separate parameter configuration file or by
providing alternate parameter specifications in Analysis: sections of the program’s input
file, or by providing alternative parameter specifications as command-line arguments (cf.
the simrisc(1) man-page)
FILES
o ~/.config/simrisc: the default location of the program’s configuration file;
o the simrisc distribution archive contains the default configuration file as
simrisc-VERSION/stdconfig/simrisc, where VERSION is replaced by simrisc’s actual
release version;
o when installing simrisc using Linux distribution archives (e.g., .deb files) the
default configuration file is commonly available as
/usr/shared/doc/simrisc/simrisc.gz
SEE ALSO
simrisc(1)
BUGS
Versions before version 15.03.00 should not be used for lung cancer simulations. The bug
invalidating lung cancer simulations was repaired in version 15.03.00.
COPYRIGHT
This is free software, distributed under the terms of the GNU General Public License
(GPL).
AUTHOR
Frank B. Brokken (f.b.brokken@rug.nl),