Transcript 2011 WHO Drug User Group Presentation

How to Talk to Your Statistician…
Reaching a Common Understanding
George B. Stoms
Vital Systems, Inc.
[email protected]
(847) 458-2900 x222
Annual US WHo Drug Dictionary user group meeting, October 27, 2011
Slide 1
Before we begin…
Keeping
Roles &
Responsibilities
in Perspective…
Annual US WHo Drug Dictionary user group meeting, October 27, 2011
Slide 2
Before we begin…
The
Statistician’s
Nightmare…
Annual US WHo Drug Dictionary user group meeting, October 27, 2011
Slide 3
Before we begin…
Every
Non-Statistician’s
Dream…?
Annual US WHo Drug Dictionary user group meeting, October 27, 2011
Slide 4
UMC User Group Survey
A recent survey of WHO Drug Dictionary Users provided
some insight into the “state” of use within companies.
As we go through this, please think about what is done at
your company.
Source:
WHO Drug Dictionary - European User Group
Presentation by Petra Barth
Annual US WHo Drug Dictionary user group meeting, October 27, 2011
Slide 5
Preliminary result from survey
• Generally happy with the quality and quantity of
the communication between coders analysis –
but:
– involve coders in meetings
– Coders should be included in meetings
– Coders and analysis team not always invited or
present at all internal team meetings
– The coders (dictionary experts) should be brought in
more often for consultation.
– An actual meeting with statistics discussing the
analysis plan, dictionary version being used,
conventions,
– Additional training would be helpful so that we each
understand one another's jobs. The industry tends to
work in silos and not see the big picture.
Annual US WHo Drug Dictionary user group meeting, October 27, 2011
Slide 6
The expert
In your organization – who is the ‘dictionary expert’?
Senior coder
Clinical Data
Manager
57%
Statistician
5%
Other...
39%
Annual US WHo Drug Dictionary user group meeting, October 27, 2011
24%
Slide 7
The expert
Is the dictionary expert
and/or coder involved in:
The development of the Study Protocol
The definition of Medications of Interest
The Statistical Analysis Plan
The definition of tables that include concomitant
medication
The actual analysis of concomitant medication
data at study end
Annual US WHo Drug Dictionary user group meeting, October 27, 2011
Yes
No
18%
70%
47%
40%
20%
70%
40%
47%
28%
62%
Slide 8
ATC assigment
Does your company require the coders to
select an ATC class that corresponds to the
indication?
Yes
86%
No
9%
Don't know
5%
Annual US WHo Drug Dictionary user group meeting, October 27, 2011
Slide 9
ATC - process
What is the process used for manual ATC coding?
Select an ATC that best captures the indication for
each time a medication is taken.
(One per incidence.)
Select an ATC that best captures the "typical"
indication for a medication in this trial.
(One per medication per trial.)
Select an ATC that best captures the "typical"
indication for a medication in all trials conducted by
the company. (One per medication per company.)
Annual US WHo Drug Dictionary user group meeting, October 27, 2011
82%
5%
5%
Slide 10
ATC – if it is not available
• ATC selection is sometimes difficult or
impossible – for example if none of the
available ATC classes fit the indication or if
no indication is given. Does your
organization have a principle for how to
handle this?
– Select an ATC that captures the "typical"
indication
– query the site for more specifics
Annual US WHo Drug Dictionary user group meeting, October 27, 2011
Slide 11
ConMed lists
When a list of concomitant medication is sorted by ATC
class – how is it done?
A programmatic merge is done with all applicable
ATC codes based on a collected Drug Code
The table is based on an ATC class that is selected
by a coder based on the indication -
67%
We don’t sort lists by ATC
22%
Don’t know
11%
Annual US WHo Drug Dictionary user group meeting, October 27, 2011
0%
Slide 12
Presentation and Analysis of ConMeds
There are important distinctions between:
DRUG CLASS
INDICATION
Similar Anatomic Target / Action
Purpose for taking
this particular
instance of dosing
Similar Therapeutic Purposes
Similar Pharmacologic Form
Similar Chemical Structures
Annual US WHo Drug Dictionary user group meeting, October 27, 2011
Slide 13
CM Coding to ATC…
CRF
CM
DrugCode
WHO Drug
(version)
CMDECOD
CMCLAS
Medications in a
given Drug Class
Annual US WHo Drug Dictionary user group meeting, October 27, 2011
Slide 14
CDISC SDTM: ATC codes
“By knowing the dictionary and version used, the reviewer will be able to obtain
intermediate levels in a hierarchy (as in MedDRA), or a drug’s ATC codes (as in
WHO Drug). The dictionary version should be listed in the Comments column
of the Define data Definition document.”
• Implementation Guide 3.1.1
– “CMDECOD with the drug’s generic name, and CMCLAS with the drug
class only if the dictionary used codes drugs to a single class. When
using WHODRUG, for example, CMCLAS would not be filled since a
drug may have multiple classes.”
– “Use only when the dictionary used codes to a single class. If using a
dictionary that allows links to multiple classes, then omit CMCLAS from
the dataset. For example, sponsors who use WHO Drug, which allows
links from a medication to multiple ATC codes, would not include
CMCLAS.”
• Implementation Guide 3.1.2
– “CMDECOD with the drug's generic name, and CMCLAS with the drug
class used for the sponsor’s analysis and summary tables. If coding to
multiple classes, follow assumption 4.1.2.8.1 or omit CMCLAS.”
Annual US WHo Drug Dictionary user group meeting, October 27, 2011
Slide 15
CM Coding to ATC…
DrugCode
CRF
CM
WHO Drug
(version)
CMDECOD
CMCLAS
Related
Record
CRF
MH
MedDRA
Related
Record
(version)
CRF
AE
LLT
PT
Meaningful
Grouping
SOC
Medications
taken for…
For more information, please refer to
Oct 28, 2011 MedDRA User Group presentation
Annual US WHo Drug Dictionary user group meeting, October 27, 2011
Slide 16
“An elephant is a mouse
built to government
specifications.”
- Lazarus Long
But what should we call it when we build something to
“industry mythology” about government specifications???
Where do regulations specify coding indication to ATC?
Annual US WHo Drug Dictionary user group meeting, October 27, 2011
Slide 17
Impediments to change…
Some reluctance is due to
• Change (“We’ve always done it this way”)
– Stakeholders, Pilot Studies, Timing/Planning
• Lack of tools for SAS programmers to import
and relate relevant datasets within the dictionary
• Lack of tools for programmers to join the
dictionary to the clinical datasets
(CM, AE, MH)
• Lack of clarity on what analyses are needed by
Regulatory Authority / Company
Annual US WHo Drug Dictionary user group meeting, October 27, 2011
Slide 18
WHO Drug Dictionary (Version C)
Annual US WHo Drug Dictionary user group meeting, October 27, 2011
Slide 19
WHO Drug Dictionary (Version B2)
DD
DDA
INA
Annual US WHo Drug Dictionary user group meeting, October 27, 2011
Slide 20
SAS: 1 - Configuration Program
* SETUP DRIVE AND ROOT MAPPING;
%let drive=c:;
%let root=\data\WHOdd;
%let SasData=\SAS\sd2;
***************************************************************;
* UPDATE SOURCE;
%let UMC=\UMC\2009-03;
%let DictFiles=\9145_who_dd_mar_1_2009\B2;
* UPDATE VERSION AND FORMAT;
%let DictProduct=DD;
* DD or DDE or DDE-HERBAL;
%let DictVersion=2009-MAR;
* YYYY-MMM;
%let DictFormat=B2;
* B2 or C;
***************************************************************;
* INPUT FOLDER;
filename UMC "&drive.&root.&UMC.&DictFiles.";
* OUTPUT FOLDER;
libname SASdata "&drive.&root.&UMC.&SasData.";
%include “{Your File Location Here}\WHOdd_config.sas"/nosource2;
Annual US WHo Drug Dictionary user group meeting, October 27, 2011
DD DDA INA
Slide 21
SAS: 2a – Import DD (drug names)
1
3
data SASdata.dd;
infile umc("dd.txt") missover;
length WHOdrug $30. DrugName $45.;
input
DrugID
1- 6
Seq1
7- 8
Seq2
9 - 11
ChkDgt
12
Desig
$ 13
SourceYr
14 - 15
SourceCd $ 16 - 19
CompnyCd $ 20 - 24
NoIngred
25 - 26
SaltEstr
27
CodeYr
28 - 29
CodeQtr
30
UMCName $ 31 – 75 ;
2
label
DrugID
Seq1
Seq2
ChkDgt
Desig
SourceYr
SourceCd
CompnyCd
NoIngred
SaltEstr
CodeYr
CodeQtr
DrugName
UMCName
WHOdrug
;
="Drug Record Number"
="Sequence #1"
="Sequence #2"
="Check digit"
="Designation"
="Source Year"
="Source Code"
="Company Code"
="Number of ingredients"
="Salt/ester code"
="Year Coded"
="Quarter Coded"
="Drug name"
="UMC Full Drug Name"
="Drug Dict Version"
* STRIP OFF UMC SLASHED MODIFIERS;
DrugName=UMCName;
if ( substr(UMCName,36,1)="/" & substr(UMCName,45,1)="/" ) then DrugName=substr(UMCName,1,35);
WHOdrug="&DictProduct."||" "||"&DictVersion."||" "||"&DictFormat.";
run;
DD DDA INA
Annual US WHo Drug Dictionary user group meeting, October 27, 2011
Slide 22
SAS: 2b – Import DD (drug names)
4
** Create Indexes **;
proc datasets library=SASdata;
modify dd;
index create DrugCode=(DrugID Seq1 Seq2) DrugName Compressed;
quit;
DD DDA INA
Annual US WHo Drug Dictionary user group meeting, October 27, 2011
Slide 23
SAS: 3 – Import DDA (drug to ATC)
1
data dda;
infile umc("dda.txt") missover;
input
DrugID
1- 6
Seq1
7- 8
Seq2
9 - 11
ChkDgt
12
ATCcode $ 13 - 19
CodeYr
20 - 21
CodeQtr
22
ATCflag $ 23
;
2
label
DrugID
Seq1
Seq2
ChkDgt
ATCcode
CodeYr
CodeQtr
ATCflag
;
run;
="Drug Record Number"
="Sequence #1"
="Sequence #2"
="Check Digit"
="ATC Code"
="Year Coded"
="Quarter Coded"
="Official ATC Code"
DD DDA INA
Annual US WHo Drug Dictionary user group meeting, October 27, 2011
Slide 24
SAS: 4 – Import INA
1 data atc;
length ATCcode $7 ATCLevel $1 ATCText $50;
infile umc("ina.txt") missover;
input @1 ATCcode $7. @8 ATCLevel $1. @9 ATCText $50.;
run;
;
2
** Create Indexes **;
proc datasets library=Work;
modify atc;
index create ATCcode;
quit;
DD DDA INA
Annual US WHo Drug Dictionary user group meeting, October 27, 2011
Slide 25
SAS: 5 – Import / Join ATC Levels
1
proc sql;
** Create the ATC_levels table **;
create table atc_levels as
select
a.ATCcode as ATCcode, b.ATCcode as ATC1code, b.ATCtext as ATC1text,
case when c.ATCcode = b.ATCcode then "" else c.ATCcode end as ATC2code,
case when c.ATCcode = b.ATCcode then "" else c.ATCtext end as ATC2text,
case when d.ATCcode = c.ATCcode then "" else d.ATCcode end as ATC3code,
case when d.ATCcode = c.ATCcode then "" else d.ATCtext end as ATC3text,
case when e.ATCcode = d.ATCcode then "" else e.ATCcode end as ATC4code,
case when e.ATCcode = d.ATCcode then "" else e.ATCtext end as ATC4text
2
from
(select * from atc) a
left join
atc b
on substr(a.ATCcode,1,1) = b.ATCcode
left join
atc c
on substr(a.ATCcode,1,3) = c.ATCcode
4
** Create index on atc_levels **;
proc datasets lib=work;
modify atc_levels;
index create ATCcode;
quit;
Annual US WHo Drug Dictionary user group meeting, October 27, 2011
3
left join
atc d
on substr(a.ATCcode,1,4) = d.ATCcode
left join
atc e
on substr(a.ATCcode,1) = e.ATCcode;
quit;
DD DDA INA
Slide 26
SAS: 6 – Import / Link Drug with ATC levels
1
2
proc sql;
create table SASdata.drug_atc as
select a.DrugID, a.ATCcode, b.ATC1code, b.ATC1text,
b.ATC2code, b.ATC2text,
b.ATC3code, b.ATC3text,
b.ATC4code, b.ATC4text
from dda a
left join atc_levels b
on a.ATCcode=b.ATCcode
where a.seq1<=001 and a.seq2<=001
order by a.drugid
;
quit;
** Create index **;
proc datasets lib=SASdata;
modify drug_atc;
index create DrugID ATCcode;
quit;
Annual US WHo Drug Dictionary user group meeting, October 27, 2011
DD DDA INA
Slide 27
SAS: 7 – Analysis: Many to Many Merge
libname whodd
libname sasout
“{Your Drive Mapping Here – where WHOdd is}";
“{Your Drive Mapping Here – where study data is}";
*** START SAS CODE - MANY TO MANY MERGE (CM & ATC)
**********************************************************************************;
proc sql;
create table sasout.cm_ATC as
select a.*, b.*
CM
from sasout.cm_coded_DrugID a
LEFT JOIN whodd.drug_atc(rename=(drugid=who_drugid)) b
on a.drugid=b.who_drugid;
quit;
run;
*** END SAS CODE - MANY TO MANY MERGE
**********************************************************************************;
DD DDA INA
Annual US WHo Drug Dictionary user group meeting, October 27, 2011
Slide 28
The Result?
• Tables: Grouping by True (all) Drug Class
• Tables: Grouping by True (actual)
Indication from MH/AE
• Analyses: Avoids missed “Drug Class”
if taken for another indication or off-label
• Less work for Coders
• Less work for SAS Programmers
• Less work for Medical Writers
Annual US WHo Drug Dictionary user group meeting, October 27, 2011
Slide 29
How to Talk to Your Statistician…
Reaching a Common Understanding
George B. Stoms
Vital Systems, Inc.
[email protected]
(847) 458-2900 x222
Annual US WHo Drug Dictionary user group meeting, October 27, 2011
Slide 30