THRioTHRio

Antonio G F PachecoAntonio G F Pacheco

THRioTHRio

OutlineOutline– Database setupDatabase setup

Creating a master table with main outcomesCreating a master table with main outcomes

– Mortality recovery with linkageMortality recovery with linkageIssues and differences between unitsIssues and differences between units

THRioTHRio

Database

THRioTHRio

We needed to evaluate the interventionWe needed to evaluate the intervention– Intervention itself is Intervention itself is training professionals and training professionals and

facilitate guidelines implementationfacilitate guidelines implementationRequest TST for eligible patientsRequest TST for eligible patients

Give IPT for eligible patientsGive IPT for eligible patients

– First approachFirst approachPercentagesPercentages

Given eligible patients for TSTGiven eligible patients for TST

Given eligible patients for IPTGiven eligible patients for IPT

– There are problems with this approachThere are problems with this approach

THRioTHRio

IssuesIssues– There is a lead time between training and There is a lead time between training and

following guidelinesfollowing guidelinesThat’s variable for each clinicThat’s variable for each clinic

– Frequency with which patients return to Frequency with which patients return to clinicclinic

– Logistic problems within the clinicLogistic problems within the clinicTST is not placed every dayTST is not placed every day

To start IPT, TB has to be ruled outTo start IPT, TB has to be ruled out– It could take a long time to get a chest X-ray!!!It could take a long time to get a chest X-ray!!!

THRioTHRio

We thought we would have to take time into We thought we would have to take time into account!account!

Instead of percentages, ratesInstead of percentages, rates

The process a patient goes through is The process a patient goes through is pretty complexpretty complex– There are dynamics issues involvedThere are dynamics issues involved

We tried to understand the dynamics firstWe tried to understand the dynamics first

THRioTHRio

Understanding the dynamics of patientsUnderstanding the dynamics of patients– Patients may go through several ‘states’Patients may go through several ‘states’– Events of interest are all dated Events of interest are all dated – It is possible to calculate transition ratesIt is possible to calculate transition rates– It would be useful for process analysisIt would be useful for process analysis

Taking time into accountTaking time into account

– Let’s see it schematically…Let’s see it schematically…

DynamicsDynamics

THRioTHRio

Main table generated by the systemMain table generated by the system– Based on the schematic part onlyBased on the schematic part only– Takes info from several tablesTakes info from several tables– Lots of programming involvedLots of programming involved

9 SQL views9 SQL views

Delphi (Pascal) programmingDelphi (Pascal) programming

> 1000 lines of code> 1000 lines of code

– Computationally-intensiveComputationally-intensiveAbout 40 min in a AMD 2 x 1.6 GHz with 2Gb RAMAbout 40 min in a AMD 2 x 1.6 GHz with 2Gb RAM

THRioTHRio

Other outcomes includedOther outcomes included– TB outcomesTB outcomes– IPT outcomesIPT outcomes– 20 different codes (with dates)20 different codes (with dates)– Long format databaseLong format database

Let’s see an example with some fake Let’s see an example with some fake data…data…

THRioTHRio

Actually now it is easy to extend itActually now it is easy to extend it– Implemented in PythonImplemented in Python

Mainly date functionsMainly date functions

– Could easily be extended in other languages (e.g. SAS)Could easily be extended in other languages (e.g. SAS)

Extra info from patientsExtra info from patients– HAARTHAART– CD4CD4– VLVL

Extra info from studyExtra info from study– Intervention statusIntervention status

THRioTHRio

Let’s see one script…Let’s see one script…

THRioTHRio

Now we can calculate ratesNow we can calculate rates

Can present data as a survival analysisCan present data as a survival analysis

Compare pre- and post-interventionCompare pre- and post-intervention

Calendar x non-calendar analysisCalendar x non-calendar analysis– Dynamics of the studyDynamics of the study– Dynamics of the interventionDynamics of the intervention

Can be presented by clinic as wellCan be presented by clinic as well

THRioTHRio

0 20 40 60 80 100

0.0

0.2

0.4

0.6

0.8

1.0

Weeks

Pro

port

ion

with

no

PP

D

Pre-interventionPost-intervention

0 20 40 60 80 100

0.0

0.2

0.4

0.6

0.8

1.0

Weeks

Pro

port

ion

with

no

PP

D

Pre-interventionPost-intervention

THRioTHRio

0 20 40 60 80 100

0.0

0.2

0.4

0.6

0.8

1.0

Weeks

Pro

porti

on w

ith n

o IP

T

Pre-interventionPost-ntervention

0 20 40 60 80 100

0.0

0.2

0.4

0.6

0.8

1.0

Weeks

Pro

porti

on w

ith n

o IP

T

Pre-interventionPost-ntervention

THRioTHRio

0 10 20 30 40 50

0.0

0.4

0.8

Weeks

Pro

port

ion

with

no

PP

D

0 20 40 60 80

0.0

0.4

0.8

Weeks

Pro

port

ion

with

no

PP

D

0 10 20 30 40 50 60

0.0

0.4

0.8

Weeks

Pro

port

ion

with

no

IPT

0 20 40 60 80 100

0.0

0.4

0.8

Weeks

Pro

port

ion

with

no

IPT

THRioTHRio

Death Rates

THRioTHRio

Death rates over time in our cohortDeath rates over time in our cohort– How many deaths are we missing?How many deaths are we missing?

With linkage we are able to improve the With linkage we are able to improve the numbersnumbers– But how much?But how much?– Is our death rate reasonable?Is our death rate reasonable?– Are there differences over time?Are there differences over time?– Are there differences across units?Are there differences across units?

THRioTHRio

Patients known to be dead at data Patients known to be dead at data abstractionabstraction– Between Sep ’03 and Sep ’05Between Sep ’03 and Sep ’05

Abstracted as ‘inactive’Abstracted as ‘inactive’

– In the beginning not even after Sep ’05In the beginning not even after Sep ’05– We started recovering themWe started recovering them

Since Sep ‘03Since Sep ‘03

No data abstracted if patients did not have No data abstracted if patients did not have a visit after Sep ‘03a visit after Sep ‘03

THRioTHRio

ProblemProblem– These patients are not included in the analysesThese patients are not included in the analyses– Potential biases on resultsPotential biases on results– Linkage with main database would failLinkage with main database would fail

If we don’t even have names or DOBsIf we don’t even have names or DOBs

Main biasesMain biases– Outcomes unrelated with deathsOutcomes unrelated with deaths– Outcomes associated with deathsOutcomes associated with deaths– Death as an outcomeDeath as an outcome

THRioTHRio

Overall death rates:Overall death rates:– From Sep ’03-Aug ’05From Sep ’03-Aug ’05

1.95/100 pys1.95/100 pys

– From Sep ’05-Mar ’07From Sep ’05-Mar ’073.49/100 pys3.49/100 pys

The problem is: there is no reason to The problem is: there is no reason to believe the rates are increasingbelieve the rates are increasing– If we are missing during the study, it is much If we are missing during the study, it is much

worse before it began!worse before it began!

Let’s see the rates per year…Let’s see the rates per year…

THRioTHRio0

12

34

5

Death rates for 1-year periods starting 1 Sep 2003

Start period

Ra

tes/

10

0 p

ers

on

-yea

rs

1Jan2004 1Jul2004 1Jan2005 2Jul2005 1Jan2006 2Jul2006

THRioTHRio

To better understand what’s going onTo better understand what’s going on– Rates per 4-month periods from Jan ’03-Mar Rates per 4-month periods from Jan ’03-Mar

’07’07– Number of deathsNumber of deaths– Person-years contributionPerson-years contribution

There are at least 3 things to be There are at least 3 things to be explained…explained…

01

23

45

Death rates and 95% CIs per 4-month periods since Jan '03

Start period

Ra

tes/

10

0 p

ers

on

-ye

ars

1Jan2004 1Jan2005 1Jan2006

THRioTHRio

Deaths and person-year contributions

Start period

De

ath

s

01

00

02

00

03

00

04

00

05

00

0

Pe

rso

n-y

ea

rs

2004 2005 2006

05

01

00

15

02

00

25

0

DeathsPYs

THRioTHRio

THRioTHRio0

.00

.10

.20

.30

.4

Person-years contribution per patient

Start period

Me

an

PY

s

1Jan2004 1Jan2005 1Jan2006

THRioTHRio

What about differences among units?What about differences among units?– Let’s try to see the issues of person-time and Let’s try to see the issues of person-time and

deaths per unitsdeaths per units– Starting with the person-years…Starting with the person-years…

THRioTHRioPerson-years contribution per patient for each 4-month period per unit

Unit

Me

an

PY

s

0.0

0.1

0.2

0.3

0.4

0.5

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29

Last period10th and 11th periodsOther periods

THRioTHRio

The mean contribution is lower for half of The mean contribution is lower for half of the unitsthe units– This is an operational issue of the way data is This is an operational issue of the way data is

collected in this studycollected in this study

For the 10For the 10thth and 11 and 11thth periods, it doesn’t periods, it doesn’t seem that badseem that bad

For deaths, if we exclude the 1For deaths, if we exclude the 1stst, 2, 2ndnd and and last periods, we can compare the rates per last periods, we can compare the rates per unitunit

THRioTHRio

Let’s see the death ratesLet’s see the death rates– Excluding the 1Excluding the 1stst, 2, 2ndnd periods periods

– Using 9Using 9thth, 10, 10thth and 11 and 11thth periods as the periods as the standard death ratestandard death rate

Rates and 95% CIs per unitRates and 95% CIs per unit

A little underestimatedA little underestimated

– Let’s compare the death rates in the Let’s compare the death rates in the other periods per unitother periods per unit

How it is evolving over timeHow it is evolving over time

66thth and 7 and 7thth periods problem periods problem

THRioTHRioDeath rates and 95% CIs for the first year of study

comparing with the previous 2 years

Unit

De

ath

Ra

tes/

10

0 P

Ys

02

46

81

01

21

4

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29

Sep 05-Aug 06Sep 03-Aug 05

THRioTHRioDeath rates and 95% CIs for the first year of study

comparing with the previous 2 years

Unit

De

ath

Ra

tes/

10

0 P

Ys

02

46

81

01

21

4

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29

Jan 06-Aug 06Sep 03-Aug 05Sep 05-Dec 05

THRioTHRio

In fact some units caught up earlierIn fact some units caught up earlier– Majority did notMajority did not– Even the ones that are within the CIs are Even the ones that are within the CIs are

consistently lower than the reference rateconsistently lower than the reference rate– 7 units have similar rates7 units have similar rates– ProblemProblem

Some units Some units remove remove charts from archives charts from archives soon after the patient is known to be deadsoon after the patient is known to be dead

Let’s look at those periods…Let’s look at those periods…

THRioTHRioDeath rates and 95% CIs for the first year of study

comparing with the 6th and 7th periods

Unit

De

ath

Ra

tes/

10

0 P

Ys

02

46

81

01

21

4

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29

6

6

6

6

6

6

6

6

6

6 6 6

6

6

6

6

6

6

6

6

6

6

6

6

6

6

6

6

6

7

7

7

7

7

7

77

7

7 7

7

7

7

7

7

7

7 7

7

77

7

7

77

7

7

7

THRioTHRio

Let’s try to see all of them over time…Let’s try to see all of them over time…

THRioTHRioDeath rates per 4-month periods per unit between Sep 03 and Aug 05

and during the fisrt year of the study

Unit

De

ath

Ra

tes/

10

0 P

Ys

02

46

8

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29

Sep 05-Aug 06Sep 03-Aug 05

THRioTHRio

So far, it looks a bad idea to use the So far, it looks a bad idea to use the time period before the study began to time period before the study began to study mortalitystudy mortality

What could be done to improve that?What could be done to improve that?– Run linkage with inactive patientsRun linkage with inactive patients

We wouldn’t have all the infoWe wouldn’t have all the info

But could at least learn about vital statusBut could at least learn about vital status

– Would help for Sep ’03 to Dec ‘05Would help for Sep ’03 to Dec ‘05

THRioTHRio

What about the mortality after the What about the mortality after the study began?study began?

My guess is that we will have about My guess is that we will have about 3.6/100 pys3.6/100 pys

Let’s see where it comes fromLet’s see where it comes from

Deaths and person-year contributions

Start period

De

ath

s

01

00

02

00

03

00

04

00

05

00

0

Pe

rso

n-y

ea

rs

2004 2005 2006

05

01

00

15

02

00

25

0

DeathsPYs

THRioTHRio

THRioTHRio

Further stepsFurther steps– Compare that rate with rates in the Compare that rate with rates in the

literatureliterature

– Stratify them by HAART use and CD4 Stratify them by HAART use and CD4 countscounts

See if rates per stratum are reasonableSee if rates per stratum are reasonable

Also compare with other studiesAlso compare with other studies