Annual US WHo Drug Dictionary user group meeting, October 27, 2011 Slide 1 How to Talk to Your Statistician… Reaching a Common Understanding George B

Annual US WHo Drug Dictionary user group meeting, October 27, 2011 Slide 1

How to Talk to Your Statistician… Reaching a Common Understanding

George B. Stoms

Vital Systems, [email protected]

(847) 458-2900 x222


Before we begin…

KeepingRoles &Responsibilitiesin Perspective…


Before we begin…

The Statistician’s Nightmare…


Before we begin…

Every Non-Statistician’s Dream…?


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


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.


The expert

In your organization – who is the ‘dictionary expert’?

Senior coder 57%Clinical Data Manager 24%

Statistician 5%

Other... 39%


The expert

Is the dictionary expert and/or coder involved in:

Yes No

The development of the Study Protocol18% 70%

The definition of Medications of Interest47% 40%

The Statistical Analysis Plan20% 70%

The definition of tables that include concomitant medication 40% 47%The actual analysis of concomitant medication data at study end 28% 62%


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%


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.) 82%Select an ATC that best captures the "typical" indication for a medication in this trial. (One per medication per trial.) 5%Select an ATC that best captures the "typical" indication for a medication in all trials conducted by the company. (One per medication per company.) 5%


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


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

0%

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%


Presentation and Analysis of ConMeds

There are important distinctions between:

DRUG CLASS INDICATION

Similar Anatomic Target / Action

Similar Therapeutic PurposesSimilar Pharmacologic Form

Similar Chemical Structures

Purpose for taking this particular instance of dosing


CM Coding to ATC…

CRFCM WHO Drug

(version) CMDECOD

DrugCode

CMCLAS

ATC #2?

ATC #1?

ATC #3?

Medications in a given Drug Class


CDISC SDTM: ATC codes

• 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.”

“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.”


CM Coding to ATC…

CRFCM

CRFMH

CRFAE

MedDRA(version)

WHO Drug(version)

Related Record

Related Record

CMDECOD

DrugCode

CMCLAS

PT

LLT

SOC

MeaningfulGrouping

Medications taken for…

For more information, please refer toOct 28, 2011 MedDRA User Group presentation


“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?


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


WHO Drug Dictionary (Version C)


WHO Drug Dictionary (Version B2)

INA

DDA

DD


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;DD INADDA


SAS: 2a – Import DD (drug names)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 ;

label DrugID ="Drug Record Number" Seq1 ="Sequence #1" Seq2 ="Sequence #2" ChkDgt ="Check digit" Desig ="Designation" SourceYr ="Source Year" SourceCd ="Source Code" CompnyCd ="Company Code" NoIngred ="Number of ingredients" SaltEstr ="Salt/ester code" CodeYr ="Year Coded" CodeQtr ="Quarter Coded" DrugName ="Drug name" UMCName ="UMC Full Drug Name" WHOdrug ="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;

1 2

3

DD INADDA


SAS: 2b – Import DD (drug names) ** Create Indexes **; proc datasets library=SASdata; modify dd; index create DrugCode=(DrugID Seq1 Seq2) DrugName Compressed; quit;

4

DD INADDA


SAS: 3 – Import DDA (drug to ATC) 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 ;

label DrugID ="Drug Record Number" Seq1 ="Sequence #1" Seq2 ="Sequence #2" ChkDgt ="Check Digit" ATCcode ="ATC Code" CodeYr ="Year Coded" CodeQtr ="Quarter Coded" ATCflag ="Official ATC Code" ; run;

1 2

DD INADDA


SAS: 4 – Import INA 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; ;

1

2 ** Create Indexes **; proc datasets library=Work; modify atc; index create ATCcode; quit;

DD INADDA


SAS: 5 – Import / Join ATC Levelsproc sql; ** Create the ATC_levels table **;create table atc_levels asselect 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

1

2 from (select * from atc) aleft join atc b on substr(a.ATCcode,1,1) = b.ATCcode left join atc c on substr(a.ATCcode,1,3) = c.ATCcode

left join atc d on substr(a.ATCcode,1,4) = d.ATCcode left join atc e on substr(a.ATCcode,1) = e.ATCcode; quit;

3

** Create index on atc_levels **; proc datasets lib=work; modify atc_levels; index create ATCcode; quit;

4

DD INADDA


SAS: 6 – Import / Link Drug with ATC levels 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;

1

2** Create index **; proc datasets lib=SASdata; modify drug_atc; index create DrugID ATCcode; quit; DD INADDA


SAS: 7 – Analysis: Many to Many Merge

libname whodd “{Your Drive Mapping Here – where WHOdd is}";libname sasout “{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.* 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 INADDA

CM


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


How to Talk to Your Statistician… Reaching a Common Understanding

George B. Stoms

Vital Systems, [email protected]

(847) 458-2900 x222

Documents

Annual US WHo Drug Dictionary user group meeting, October 27, 2011 Slide 1 How to Talk to Your Statistician… Reaching a Common Understanding George B