Clinical Practice ImprovementNetwork for Early Psychosis

CPIN-EP

Stanley Catts

University of Queensland

Tenth NSW Early Psychosis Forum

30 October 2007

Westmead

Overview

Evaluating early psychosis intervention– Naturalistic evidence– Clinical trials– Observational studies

Description of CPIN-EP

CPIN-EP results– Performance of CPIN-EP methodology– Cohort description– Impact of service model on patient registration

rates and DUP– Impact of clinical practice and family outcomes

Interim conclusions

EPI: Naturalistic evidence

Early disease course is the strongestpredictor of long-term outcome forpsychotic disorders1

Remission of the first psychotic episodeand avoidance of relapse during the firsttwo years of treatment may reduce long-term disability up to 30% irrespective ofbaseline patient characteristics2

1Harrison et al., 2001, Br J Psychiatry, 178,506-5172Harrison et al., 1996, Psychol Med, 26,697-705

EPI: Naturalistic evidence

The chance of full recovery reduces witheach relapse of psychosis1

The likelihood of relapse increases overtime2

1Wiersma et al., 1998, Schizophr Bull, 24,75-852Robinson et al., 1999, Arch Gen Psychiatry, 56,241-247

EPI: Naturalistic evidence

More patients respond well to medicationin the first episode (about 80%)1 comparedto subsequent episodes (about 50%)2

Initial response occurs at lower doses ofmedication3 and psychosocial intervention

1Lieberman et al., 1993, Arch Gen Psychiatry, 50,369-3762Lieberman et al., 1996, J Clin Psychiatry, 57,suppl 9,5-93Merlo et al., 2002, J Clin Psychiatry, 63,885-891

EPI: Clinical trials

“There was insufficient or no evidencefrom RCTs to support the benefits ofspecialist EPI teams, and no evidencefrom clinical trials to support the benefits ofearly detection of patients in their firstepisode of psychosis”1

“There is now quantitative evidence … thatenriched interventions for patients withrecent-onset psychosis are significantlymore effective than standard care … overa period of about one year”2

1Marshall & Rathbone, Cochrane Database, 2006, issue 42Harvey et al., (2007) Can J Psychiatry 52:464-472

Clinical trials:The OPUS Study

Design1,2

– 547 patients aged 16/18 - 45 presenting (1/98-12/00) for the first time with ICD-diagnosed nonaffective non-organic psychosis living in 2 districtsof Copenhagen and one in Aahus wererandomised to:

• Integrated Treatment (IT: specialist team using ACT,1:10; family therapy for 18 months; SST fro 12months)

• Standard Treatment (ST; standard casemanagement, 1:25; no family therapy or SST

– Patients have been followed-up for five years

1. Jorgensen et al (2000) Soc Psychiatry Psychiatr Epidemiol 35:283-287

2. Thorup at al (2005) Schiz Res 79:95-105

Clinical trials:The OPUS Study

163 (60%)206 (75%)Patients interviewed

At 24 months:

87 (62%)137 (74%)Carers interviewed4

192 (71%)227 (83%)Patients interviewed3

At 12 months:

140185Eligible carers

65%67%Schizophrenia

5345.5Median DUP (wks)

60%58%Males

26.626.6Mean age

272275At baseline (n)

STITSUBJECTS

3. Petersen et al (2005) Brit J Psychiatr 187 (Suppl 48):s98-103

4. Jeppesen at al (2005) Brit J Psychiatr 187 (Suppl 48):s85-90

Clinical trials:The OPUS Study

Results at 12 monthsOutcomes favoured IT significantly IT ST

M=1.13SD=0.4

M=1.02SD=0.04

Carer burden (SBAS subscale score)4

81561Days in hospital in last 12 months

73%357%Any ‘poor outcome’

53%342%No work/study

17%310%Homeless/supervised accommodation

22%316%Patients with SUDS

17%310%Patients with GAF –s <30

35%322%Patients with SANS ss >3

20%310%Patients with SAPS s.s >3

3. Petersen et al (2005) Brit J Psychiatr 187 (Suppl 48):s98-103; 4. Jeppesen at al (2005) Brit J

Psychiatr 187 (Suppl 48):s85-90; 5. Norden et al (2003) Schiz Res 60 (Suppl): s297

Carer satisfaction (Mean IT vs ST difference score on modified CSQ) = 3.4

Clinical trials:The OPUS Study

Results at 24 months:The following outcomes significantly favoured IT vs ST:

• Mean SAPS score 1.07 vs 1.29

• Mean SANS score 1.42 vs 1.84

The following outcomes favoured IT vs ST at level of a trend:

• Days in hospital in past 2 years

Differences in treatment at 24 months:Number of contacts with primary staff: IT = 77 vs ST = 27

Relatives involved in treatment: IT = 61% vs ST = 20%

Similar medication doses were used and similar number of

patients in IT vs ST had stopped medication at 2 years (30%)

Thorup at al (2005) Schiz Res 79:95-105

Clinical trials:The OPUS Study

Results at 5 years:“The results show no difference between treatment

groups at five-year follow-up. … It seems that twoyears of intensive treatment in the early phases ofpsychosis is not enough to ensure a good long-term outcome.”

Bertelsen et al (2006) Schiz Res 86:S43

EPI: Observational studies

Demonstrating treatment effects of EPI in RCTs is difficultbecause– A proximal element of EPI operates through a chain of processes

aiming to improve a distal health outcome

– The proximal application of EPI is temporally distant from long-termoutcomes of interest

– In the absence of agreement about the essential ingredients foreffective EPI, the composition of programs is usually dissimilar,preventing ready meta-analytic evaluation

Observational studies can clarify essential components ofintervention and allow examination of the effect of adiscrete intervention on a relevant proximal process,providing information for designing effective EPI programsand sound RCTs

EPI: Observational studies

Pros– Real-world treatment can be observed

without experimental intervention– All patients may be included– Relatively inexpensive– Can be carried out in a quality assurance

framework

Cons– Confounding and biases are inherent,

necessitating complicated analyticapproaches

– Any finding made has to be confirmedexperimentally in an RCT

An Australian multi-siteevaluation of EP programs

Chief Investigators

Stanley V. Catts*

Brian I. O’Toole**

Vaughan J. Carr***

Associate Investigators

Terry Lewin***

Amanda Neil***

Meredith Harris****

The NHMRC Clinical Practice Improvement

Network for Early Psychosis

*U of Queensland; **U of Sydney; *** U of Newcastle; ****ORYGEN Youth Health

The NHMRC Clinical PracticeImprovement Network

for Early Psychosis (CPIN-EP)

CPIN-EP is an epidemiological study ofthe effect of exposure to guideline-adherent early psychosis intervention

The study used a prospectiveobservational cohort design

Only routinely collected data was used

CPIN-EP was approved as a qualityassurance project, not requiring patientconsent

CPIN-EP has amulti-level hierarchical design

EPI teams

Observations over 6 months

Patient 2 Patient n

Clinician 1 Clinician 2 Clinician n

Level 3

Level 1

Level 2

Patient 1

Level 4

C-PINEP Data Sources

Case Manager

Feedback

Questionnaire

Service Self

Review

Instruments

Service

Census

Service Level

Patient Level

Consumer and

Carer Feedback

Questionnaires

Chart

AuditHoNOS, LSP,

Consumer

Measures

Service

Contact

Forms

Recording

Forms

Data collection protocol

Patient level data acquisition

Structured file audit by medical studentsof photocopied de-identified file noteson first six months (or till service exit) toextract:– Demographics

– CPIN-EP indicator codes

– Verbatim file recorded diagnosis (at anytime within 6 months)

– CPG-EP adherence

– Documentation quality indicators

Bulk scanning of Service Contact Formintervention list (reverse side of SCF)

Early Psychosis Indicator

On the basis of available information, are you confident that at some

point ever (including now) a diagnosis of a psychotic disorder* could be

made for this patient?

Has the patient received a

diagnosis of a psychotic disorder

more than 12 months ago?

Do you think the patient is/has

been highly likely to be

prodromal in the last 12 months?

YES NO

YESNO NO YES

2

(Definite EP)

0

(Not EP)

1

(Possible EP)

* Any Axis I disorder with psychotic symptoms

0

(Not EP)

CPIN-EP results:Performance of EP indicator

(flag)

Highly likely EP Definitely EP

(prodromal) (diagnosable)

Flag 1 Flag 2

Flagging rate (n=451) 26% (n=116) 74% (n=335)

Final diagnosis within 6

months: Psychotic disorder 75% 100%

Final diagnosis within 6

months: Non-psychotic disorder 25% 0%

Final psychotic diagnosis(by detailed audit)

Schizophreniaspectrum

Other psychotic

disorder

Affectivepsychoses

Non-psychotic

disorder

FLAG 2 FLAG 1

Baseline, 3-month, 6-month measures:

HoNOS

Social and Occupational Functioning (SOFAS)or GAF/GAS

DUP Indicator (only at baseline)

Service Dropout Indicator (only at serviceseparation)

Suicide Risk

Substance Use

Relational [e.g. family] Functioning (GARF)

CPIN Clinical Indicators

Results of Reliability Analysis

= 0.82 Social and Occupational Functioning Assessment Scale

= 0.90 Global Assessment of relational functioning

= 0.91 Suicide Risk

= 0.99 Duration of Untreated Psychosis

= 0.96 EP Indicator

EP TeamINDICATOR

= 0.84

= 0.84

= 0.30

= 0.96

= 0.79

Non EP

Missing data rates

Measure Baseline Six months

(completers)

(n=451) (n=320)

HoNOS 27% 43%

SOFAS 31% 58%

GARF 33% 58%

Cannabis 36% 64%

Stimulants 43% 67%

Diagnostic information

From structured file audit:

Proportion of cases where no definite diagnosis*recorded by 6 months or service exit

35% (157/451)

Proportion of cases given an indefinite diagnosisat first assessment who did not have adocumented diagnostic review by 6 months orservice exit

57% (89/157)

*Psychosis NOS included as a definitive diagnosis

Diagnostic information

From unstructured and detailed (readingevery word in the file) file audit bymedical/nursing-trained auditors:

Proportion of cases where a definite DSMIV diagnosis* could be made with relativecertainty

~ 100% (449/451)

*Psychosis NOS included as a definitivediagnosis

Total sample baselinecharacteristics (n=451)

Age and Gender

Mean Age (at first contact with service) 21.61

Age Range 13-56

Gender (Male) 64%

Indigenous

Non-indigenous 97.8%

Indigenous 2.2%

Total sample baselinecharacteristics (n=451)

Living Arrangements

With family 66.1%

With partner 9.3%

With friends 7.5%

Alone 7.3%

Homeless 9.8%

Employment

Employed 37.9%

Unemployed 62.1%

Total sample baselinecharacteristics (n=451)

Referral Sources

General Practitioners 16.4%

Police 6.0%

Family/Friends/Self 39.7%

Other 37.9%

First Contact Setting

Outpatient 55.6%

Inpatient/Emergency 44.3%

Total sample baselinecharacteristics (n=451)

Duration of Untreated Psychosis

Delusions 8.18 months (10.96 SD)

Hallucinations 9.77 months (12.52 SD)

Other Symptoms 14.46 months (12.84 SD)

EP detection rate by AMHS(sexes separated)

0

50

100

150

200

250

300

1 2 3 4 5 6 7 8

Males

Female

Fla

g 2

pe

r 1

00

,00

0 p

eo

ple

EP detection rate by AMHS(sexes combined)

0

50

100

150

200

1 2 3 4 5 6 7 8

Fla

g 2

am

on

gs

t 1

8-2

5 y

ea

r o

lds

pe

r 1

00

,00

0 p

eo

ple

AMHS 1 and 2 have relatively long-established EPI functions (shading)

Flag 1 + 2 DSM IV grouping byAMHS (up to 3 Dx per patient)

3%3%3%4%12%12%8%16%

Personality

disorders - B

21%47%31%49%30%44%15%34%

Substance use

disorders

26%11%15%12%30%26%8%10%

Anxiety and non-

psychotic

depressive disorders

18%21%8%7%32%9%0%14%Affective psychoses

34%21%20%14%19%25%0%22%

Other psychotic

disorders

42%52%64%75%36%51%92%62%

Schizophrenia

spectrum

87654321DSM IV grouping

Detection rate versusservice model

AMHSs with highest recruitment ratesof EP patients:– are long-established

– have specialised function

– are fully integrated across services

Relationship betweendetection rate and DUP

If an AMHS successfully recruitsincreased numbers of EP patients yearafter year, does this in itself achieveearlier detection, as indexed by shorterDUP?

Predictors of DUP at thepatient level

Adjusted

hazard

ratioa 95% CI p value

Age at onset 1.021 0.998-1.044 0.074

Employed 1.282 0.972-1.692 0.079

Living with family 1.308 0.874-1.958 0.191

Acute mode of onset 2.012 1.319-3.068 0.001

Diagnostic group 0.007b

Affective psychoses 1.291 0.973-1.713 0.076

Other psychotic disorders 2.054 1.269-3.326 0.003

SES of residential suburb 1.001 0.999-1.003 0.194

Service model 0.030c

Extensive implementation 1.765 1.028-3.029 0.039

Some implementation 2.013 1.200-3.377 0.008aHazard ratio > 1 indicates higher risk of contact with services at any point in time and,

therefore, shorter average DUPbReference category: Schizophrenia spectrum disorderscReference category: No/Little EP model implementation

DUP and DUP-relatedcovariates, by service

1 2 3 4 5 6 7 8

DUP (months)* 10.6 7.3 11.0 7.0 7.9 16.2 9.0 6.2

mean (SD) 12.9 3.9 13.7 6.7 12.4 15.6 10.7 8.6

median 6 8 6 5 3 12 3 2

Sex (Males %) 61.2 66.7 60.3 50.0 61.6 80.6 69.4 75.0

Living with family** 88.3 81.8 91.4 92.3 69.4 74.3 88.6 86.1

Education level*** 90.8 50.5 65.3 93.9 79.1 84.4 73.5 65.6

SES (% below

median SEIFA)*** 71.5 91.7 82.4 42.5 13.7 55.6 2.8 34.3

*p< 0.05; **p<0.01; ***p<0.001

Analyses exclude service # 2, due to small cell sizes

Change (improvement) inSOFAS scores by AMHS

0

2

4

6

8

10

12

1 2 3 4 5 6 7 8

Change (improvement) inGARF scores by AMHS

0

0.5

1

1.5

2

2.5

3

3.5

4

1 2 3 4 5 6 7 8

Multi-Level Modeling

Advanced form of regression

Analyses data within naturally occurringhierarchies (e.g. child within school)

Treating all the data as though it is onelevel under-estimate standard errors –increasing chance of type I error

Hierarchy of CPIN

Level 4 Treating Team n = 19

1 :

Level 3 Clinician n =181

1 :

Level 2 Patient n = 464

1 :

Level 1 Observation n = 1086

Expressing the Hierarchy

Regression Equation

Residuals

Estimating Variance

Parameter Estimate

Standard Error

Where is the Variance ?

Level 4 Which EP Team?

0 – 2.3%

Level 3 Which EP Clinician?

0 – 1.5%

Level 2 Which EP Patient?

29 – 45 %

Level 1 What happened to the patient?

54 – 70 %

What does this mean ?

Up to 70% of the variance in six monthsSOFAS score is explained by whathappened to the patient over time(including treatment received)

If the type of service or nature of theclinician is important, the impact of thesevariables is mediated by how theyinfluence the patient’s clinical treatment

Specific conclusions (1)

Despite strong support from naturalisticstudies, so far clinical trials have notconfirmed the effectiveness of EPI inimproving long-term outcomes

CPIN-EP, an observational study, wasnot designed to evaluate theeffectiveness of EPI, rather whetherguideline-adherent EPI during the firstsix months of treatment influencesshort-term outcome

Specific conclusions (2)

CPIN-EP evaluation tools were applicableand reliable, but CPIN-EP procedureswere not followed consistently by clinicians(e.g., rating the HoNOS)

Clinicians did not derive a definitivediagnosis in more than one-third of cases

These two factors prevented CPIN-EP ingiving timely feedback as a qualityimprovement project should

Specific conclusions (3)

There were substantial differences inthe EP detection rates across services,and these differences appear to berelated to EPI service model

Differences in diagnostic profile andDUP across services appeared to besecondary to differences in detectionrate, not the other way around

Specific conclusions (4)

In the CPIN-EP study DUP and EPoutcomes were confounded, whichagain calls into question the broaderobservational literature concerning therelationship between DUP and outcome

There were substantial differences inpatient and family outcomes at 6months, and these were primarilydetermined by clinical practice andsecondarily by baseline patientcharacteristics

General conclusions

Published RCTs of EPI are not truetests of the efficacy of EPI becauseenhanced initial treatment is beingcompared to treatment as usual, notearly versus late intervention

Observational studies can informclinical practice and guide design offuture RCTs

Acknowledgements

Project teamKathy EadieRussell EvansAaron FrostBelinda Schaefer

This project is dedicated to mentalhealth consumers, carers and serviceproviders. They are the enduringinspiration for this work.