MINIM

A program for randomising patients to treatment groups in clinical trials by the method 
of minimisation  

written by    Stephen Evans  
Simon Day   
Patrick Royston  

Available from

          www.sghms.ac.uk/depts/phs/guide/randser.htm

Features

? Any number of trials may be run from one copy of MINIM(limited only by disk 
space) but we would advise that a separate disk or directory is used for each 
concurrent trial.

? Up to four treatment groups.

? Different proportions of patients in each treatment group if required.

? Any number of prognostic factors and categories for each factor (subject to a total 
of 100 categories for all factors together).

? Different 'weights' for each prognostic factor if required so that some factors can be 
treated as more important to balance for than others.


A demonstration copy is available that includes all the features of the full program but 
will not allow more than ten subjects to be randomised.
Special customised versions of the program are available:  contact SJW Evans for 
details.

Introduction

To run MINIM, you need the file 'MINIM.EXE' which is on the enclosed disk. There is 
also an example set of data called 'EXAMPLE.DAT' (from Stuart Pocock's book  
Clinical Trials: A Practical Approach, page 85; Wiley, 1983)  and there may be files 
called 'MINIM.LOG' and 'MINIM.CTL'. Copy these files into your chosen sub-directory 
(or alternatively onto a new disk and use that as the default).


MINIM does three things:
1 You can use a demonstration data set;
2 You can set up new trials for your own use;
3 You can run your own designed trials.

When using the program, MINIM offers you two options:
1 You can assign new patients to treatment groups by the method of minimisation;
2 You can tell the program that some patients have been assigned to treatment 
groups by some other method.  This is crucial if, for example, your computer is 
occasionally unavailable and a few patients have to be entered into the trial by 
simple randomisation.


To start the program, type minim, followed by carriage return (you will always need to 
press return after each instruction).

Note:In these notes, all instructions or answers to questions that you need to type  are 
shown as lower case, underlined.  
When typing, it does not matter if you use upper or lower case characters.

Demonstration File
The example given on page 85 of Pocock's book has two treatment groups and four 
prognostic factors:
Performance status, Age, Disease-free interval and Dominant metastatic lesion.
Initially, you may wish to try out the program on the example data set,
so in answer to the question

'What is the name of your data file? '
type example.dat, followed by carriage return.

Firstly, we are shown the current state of the data file (see Figure 1).

Next, you have three options:
'A' use this most often to run the program properly (ie. to use the
minimisation procedure).

'U' use this if for some reason patients have been entered into the
trial without using the program.  This may be because the computer was broken or not 
available etc.  You should not be using this routinely, but if necessary, patients can be 
forced into the data file in this way.

'S' obviously, to stop the program.

Firstly, try typing a.  You are asked:'Do you have details of a patient? '
Answer y.
Demonstration File(continued)Figure 1

CURRENT STATE OF TRIAL                                           
POCOCK; Clinical Trials. Page 85                                    

Treatment A
Treatment B
Performance status


     Ambulatory
30
31
     Non-ambulatory
10
9
Age


     Under 50
18
17
     50 & over
22
23
Disease-free interval


     Under 2 years
31
32
     2 years & over
9
8
Dominant metastatic lesion


     Visceral
19
21
     Osseous
8
7
     Soft tissue
13
12



     Totals
40
40
Grand Total
80

Press RETURN to continue 
Demonstration File (continued)

You can describe the patient as (for example) :

Ambulatory status 'Ambulatory' option 1
Age  'Under 50' option 1
Disease free interval '2 yrs & over' option 2
Dominant metastatic lesion 'Soft tissue'  option 3

Instead of typing the option numbers, you can type the text, eg.ambulatory or an 
abbreviation of it. This is shown in Figures 2a and 2b.

These options are then re-printed and you can confirm that they are correct.  If they 
are wrong, you can edit all, or some, of them as shown in Figure 3.  If you confirm the 
details to be correct, then there will be a message saying either:

'Patient allocated to Treatment A' or 'Patient allocated to Treatment B'

The patient has been allocated mostly on the basis of the method of minimisation but 
partly by pure randomisation. You can enter as many patients as you like in this way.  
When you say you have no more patients, you will be shown the updated state of the 
trial and asked if you want to stop the program.  Answer n  and you will go back to the 
three options (given above) of allocating, updating or stopping.  Now answer  y (ie. you 
do want to stop) and you will have the option of either saving the new state of the data, 
or discarding the changes.

Demonstration File(continued)
Figure 2a

   ENTERING PATIENT'S DETAILS                                            
What is the value of Performance status for this patient?

    Ambulatory
1
    Non-ambulatory
2
Value, or code in range 1 ... 2 ? (see footnote)

What is the value of Age for this patient?

    Under 50
1
    50 & over
2
Value, or code in range 1 ... 2 ?

What is the value of Disease-free interval for this patient?

Under 2 years
1
2 years & over ..
2
Value, or code in range 1 ... 2 ?


Press RETURN to continue 

footnote:instead of typing 1, we could type 'ambulatory', or any abbreviation that 
unambiguously identifies the Performance status.

Demonstration File(continued)

Figure 2b

What is the value of Dominant metastatic lesion for this patient?


     Visceral
1
     Osseous
2
     Soft tissue
3
Value, or code in range 1 ... 3 ? soft t(see footnote)


Current patient details are

1. Performance status ....... Ambulatory

2. Age ...................... Under 50

3. Diseasefree interval .... 2 years & over

4. Dominant metastatic l .... Soft tissue


Do you want to alter any of these details ? n

footnote:soft t unambiguously identifies the value of Dominant metastatic lesion.  We 
could have typed 3 instead.
Demonstration File(continued)
Figure 3
Current patient details are

1. Performance status ....... Ambulatory

2. Age ...................... Under 50

3. Disease©free interval .... 2 years & over

4. Dominant metastatic l .... Soft tissue

Do you want to alter any of these details ? y


Type the name or code number of the variable whose data is to be  altered, 
or ALL to reenter ALL data for this patient, or Q to  cancel this request:

Name, or code in range 1 ... 4 ? age


What is the value of Age for this patient?

    Under 50
1
    50 & over
2
Value, or code in range 1 ... 2 ? 50


Demonstration File(continued)

Usually you will want to save the data, but if you are showing someone how to use the 
program or perhaps you have made some errors in entering patients you may wish to 
discard the changes and leave the data as it was before starting this session.Type y to 
update the data.  The program now finishes.

You should now try starting it again (type minim) to check that the new patient(s) have 
been included in the example data set.

If instead of asking for option a to allocate patients, you asked for option u to update 
the data, exactly the same sequence is followed, except that in place of the statement 
like:

'Patient allocated to Treatment A'

you will be asked to say which treatment the patient received and they will then be 
forced into the data set under that treatment heading.  Any further patients entered by 
minimisation will then take account of such patients that may have been entered by 
simple randomisation.


Setting up a new trial

MINIM will not design trials nor check any sort of ethical, logistical or practical 
problems that may exist in your design.  It is a tool to aid in the execution of trials and 
not a tool for overcoming poor design.  As part of your trial protocol, you should have a 
list of possible prognostic factors that may affect outcome (for example, sex, age etc).  
These will be the features on which you will need to 'minimise' imbalance across 
treatment groups.

If you want to set up a new trial, get the program running and in answer to the question 

'What is the name of your data file? '

type in a new data file name (any IBM allowed file name will do). 
You could use trial.dat or trial1.dat but these may be a bit limiting as you can have 
several trials on one disk, though this is not recommended.  We advise having each 
trial on its own disk or directory.  In any event, names like asthma.dat or anaesthe.tic 
are easier to use in the long term.  (Remember to press the 'carriage return' key at the 
end of each line). Assuming you are setting up a new trial MINIM will not be able to 
find this set of data so will ask if you want to set up a new one. 
Answer y.

You now describe part of the design of the trial relating to stratification as shown 
overleaf.

Setting up a new trial(continued)

You are asked for :

1. Title:  type any text you like.

2. A list of factors you wish to minimise on:
try typing sex, which might have 3 categories, named male, female and not known.  
Each factor may be weighted as not very important (weighting=1, say) or very 
important (weighting=2 or 5 or 10 etc).  Again, remember to press the 'return key' at 
the end of each line.

3. More prognostic factors as above:
type * when you have no more of them.

4. A list of treatment groups:
try typing Treatment 1, then give it a single character symbol such as 1 or t etc.  Now a 
value for what proportion of patients you want allocated to this group (for example, you 
may have three groups and wish to allocate in the ratio 2:2:3, giving the last group 
slightly more patients).

5. More treatment groups (maximum of 4).
type * when you have no more of them.  Now you are shown an outline of your trial 
(with no patients in it!) and asked to confirm it is OK.  An example is shown in Figure 4.  
If you have made a mistake, type n and redo it, otherwise type y.

This 'structure' is now saved and you can begin your trial by following the instructions 
given earlier.
Setting up a new trial(continued)

Figure 4
CURRENT STATE OF TRIAL      
POCOCK; Clinical Trials. Page 85         

Treatment A
Treatment B
Performance status


Ambulatory
0
0
Non-ambulatory
0
0
Age


     Under 50
0
0
     50 & over
0
0
Diseasefree interval


     Under 2 years
0
0
     2 years & over
0
0
Dominant metastatic lesion


     Visceral
0
0
     Osseous
0
0
     Soft Tissue
0
0
Totals
0
0
Grand Total
0

Is that all correct?



Special Features

It may be required that the person using this program should be 'masked' to which 
treatment is going to be used.  In such cases, it is possible to encode a randomisation 
list within the program so that instead of getting a message like:
'Patient allocated to Treatment A'  a message such as:
‘Patient allocated to Treatment Pack 27' is produced.

For security reasons it is possible to have a password protected version.

Some customers have requested that the option to discard new patients' data and not 
save the new version of the data be removed.

Copies of the program to run on the Apple Macintosh can be provided.

Trials with more than four treatments are not common and very often have ethical 
objections.  There are, however, some situations where such trials are appropriate and 
versions of the program to handle more than four treatments can be supplied.

All of these options are available as one-off requests and are not provided within the 
standard program.  Contact :

Stephen J W Evans
Telephone +44 (0) 20 7927 2960
Email: Stephen.Evans@lshtm.ac.uk