Low Intensity Comparators for Interpersonal

Psychotherapy Trials

Holly A. Swartz, M.D.Yu Cheng, Ph.D.

University of Pittsburgh School of MedicinePittsburgh, PA USA

Presenter Company Consultant Research CME Speaker

H.Swartz NIMH X

Pfizer X

Servier X

SciMed X

BMS X

Disclosure

Examples of Low Intensity Comparators

• No active treatment– Wait list control (WLC)– Non-scheduled treatment control

• Non-standardized treatment– Treatment as usual (TAU)– Usual care (UC)

Characteristics of No Active Treatment Controls

• Minimum/low contact condition• Assessments only• Subjects withdrawn for clinical worsening and

offered active treatment• Expectation of eventual care (if study offers

intervention at the end of trial to those who did not receive it)

Characteristic of TAU/UC• Subjects are free to seek care in the

community• Nature of treatment received is usually

quite variable• Some studies augment the referral process• Treatment is provided outside of the

research protocol

Advantages of Low Intensity Comparators: TAU/UC

• Answers important questions:– “How does IPT compare to services as they are

provided in usual care settings?”– “Does IPT offer incremental advantages over current

practice?”• Ecological validity• Patients are afforded a range of treatment options• Bottom line– Increased external validity (generalizability) of trial– Low(er) costs for clinical trial

Disadvantages of Low Intensity Comparators: TAU/UC

• TAU/UC is very variable– Difficult to know what patients are actually getting– Unmeasured in most trials– Decreased comparability across trials*

• Does not control for nonspecific factors associated with a clinical trial– Fewer resources(financial/personnel) in community– Differential incentives for treatment engagement– Lacks Hawthorne effect of addition of study

intervention• Bottom line– Decreased internal validity of trial

*Poses additional dilemmas when comparing studies across countries where standards of community care differ

Advantages of Low Intensity Comparators: WLC

• If sample is non-treatment seeking, may be proxy for “usual care”

• Controls for the natural course of untreated illness (i.e., scientific interest)

• Low(er) costs for clinical trial• Bottom Line– Few advantages

Disadvantages of Low Intensity Comparators: WLC

• Ethical concerns– Withholding treatment from a vulnerable population

• High dropout rates (in some trials)• Does not control for non-specific factors of IPT

– Support– Contact hours– Helping relationship

• Even if IPT “wins,” you’ve shown that it is better than no treatment, which is not much of a victory

• Bottom line– Decreased internal validity– Hard to justify WLC

IPT v. WLC or Non-Scheduled Treatment: ES

Author Population Design Study Duration

Depression Measure

Effect Size1

Bolton et al., 2003

Adults with depression or depressive symptoms living in 30 villages in Uganda

IPT-G-U (n=163 ) v. TAU (n=178)

16 weeks Hopkins Symptom Checklist (modified version)

2.17

DiMascio et al., 1979

Acute depression IPT (n=17) v. IPT+AMI (n=23) v. NST (n=21) v. AMI (n=20)

16 weeks HRSD-17 2.012

O’Hara et al., 2000

Non-treatment seeking women with post-partum depression

IPT (n=48) v. WLC (n=51)

12 weeks HRSD-17 plus additional items

1.62

Rossello et al., 1999

Depressed adolescents in Puerto Rico

IPT-A (n=23) v. CBT (n=25) v. WLC (n=23)

3 months CDI 0.88

1ES calculated comparing IPT to WLC using reported values, Morris S. Estimating effect sizes from pretest-posttest-control group designs. Organizational Research Methods (2008); 11:364-386.2SD deviations not reported, therefore assumed SD=SD of other studies reporting depression scores as HRSD-17

IPT v. WLC or Non-Scheduled Treatment: NNT

Author Population Design Basis for NNT Calculation

NNT1

Bolton et al., 2003

Adults with depression or depressive symptoms living in 30 villages in Uganda

IPT-G-U (n=163 ) v. TAU (n=178)

Rate of diagnosable major depression

2

DiMascio et al., 1979

Acute depression IPT (n=17) v. IPT+AMI (n=23) v. NST (n=21) v. AMI (n=20)

N/A

O’Hara et al., 2000

Non-treatment seeking women with post-partum depression

IPT (n=48) v. WLC (n=51)

HRSD ≤6 6

Rossello et al., 1999

Depressed adolescents in Puerto Rico

IPT-A (n=23) v. CBT (n=25) v. WLC (n=23)

N/A

1NNT calculated from reported categorical response/remission rates rather than ES, as per Furukawa TA, Leucht S (2011) How to Obtain NNT from Cohen’s d: Comparison of Two Methods. PLoS ONE 6(4): 19070.doi:10.1371/journal.pone.0019070

IPT v. TAU or UC: Effect SizesAuthor Population Design Study

DurationDepression Measure

Effect Size1

Beeber et al., 2010

Newly immigrated, low income, Latina mothers with depressive symptoms whose toddlers participated EHS

In-Home IPT (n=39) v. UC (n=41)

16 weeks CES-D 0.85

Grote et al., 2009

Antenatal depression in pregnant, low income women in an obstetrics clinic

IPT-B (n=25) v. TAU (n=28)

3 months EPDS 2.37

Mufson et al., 2004

Adolescent depression in school-based mental health clinics

IPT-A (n=43) v. TAU (n=29)

12 weeks HRSD-17 0.52

Mulcahy et al. 2010

IPT-G (n=23) v. TAU (n=27) for PPD, over 8 weeks

8 weeks HRSD-17 0.84

1ES calculated comparing IPT to WLC using reported values, Morris S. Estimating effect sizes from pretest-posttest-control group designs. Organizational Research Methods (2008); 11:364-386.2ES reported in the original manuscript

IPT v. TAU or UC: Effect Sizes, cont.Author Population Design Study

DurationDepression Measure

Effect Size1

Ransom et al., 2008

HIV-AIDS infected individuals and depression-spectrum disorders in rural area

Telephone IPT (n=41) v. UC (n=38)

6 sessions BDI-II 0.42

Schulberg et al. 1996

Primary care practices IPT (n=93) V. NT (n=91) V. UC (n=92)

8 months HRSD-17 0.54

Swartz et al., 2008

Depressed mothers of children receiving psychiatric care

IPT-MOMS (n=26) v. TAU (n=21)

3 months HRSD-17 0.62

Tang et al., 2009

Depressed adolescents with suicidal risk and parasuicidal behaviors

IPT-A (n=35) 2 sessions per week v. UC (n=38)

6 weeks BDI-II 1.42

Van Schaik et al., 2006

Depressed patients ≥age 55 in primary care clinics

IPT (n=69) for 10 sessions v. TAU (n=74)

6 months MADRS 0.13

1ES calculated comparing IPT to WLC using reported values, Morris S. Estimating effect sizes from pretest-posttest-control group designs. Organizational Research Methods (2008); 11:364-386.

IPT v. TAU or UC: NNTAuthor Population Design Basis for NNT

CalculationNNT1

Beeber et al., 2010

Newly immigrated, low income, Latina mothers with depressive symptoms whose toddlers participated EHS

In-Home IPT (n=39) v. UC (n=41)

CES-D<16 3

Grote et al., 2009

Antenatal depression in pregnant, low income women in an obstetrics clinic

IPT-B (n=25) v. TAU (n=28)

≥50% improvement on EPDS

2

Mufson et al., 2004

Adolescent depression in school-based mental health clinics

IPT-A (n=43) v. TAU (n=29)

HRSD ≤6 20

Mulcahy et al. 2010

IPT-G (n=23) v. TAU (n=27) for PPD, over 8 weeks

EDPS Reliable change index for Recovered status

3

1NNT calculated from reported categorical response/remission rates rather than ES, as per Furukawa TA, Leucht S (2011) How to Obtain NNT from Cohen’s d: Comparison of Two Methods. PLoS ONE 6(4): 19070.doi:10.1371/journal.pone.0019070

IPT v. TAU or UC: NNT, cont.Author Population Design Basis for NNT

CalculationNNT1

Ransom et al., 2008

HIV-AIDS infected individuals and depression-spectrum disorders in rural area

Telephone IPT (n=41) v. UC (n=38)

Clinically meaningful change= ≥9 point reduction on BDI-II

11

Schulberg et al. 1996

Primary care practices IPT (n=93) V. NT (n=91) V. UC (n=92)

HRSD≤7 4

Swartz et al., 2008

Depressed mothers of children receiving psychiatric care

IPT-MOMS (n=26) v. TAU (n=21)

HRSD <8 8

Tang et al., 2009

Depressed adolescents with suicidal risk and parasuicidal behaviors

IPT-A (n=35) 2 sessions per week v. UC (n=38)

N/A

Van Schaik et al., 2006

Depressed patients ≥age 55 in primary care clinics

IPT (n=69) for 10 sessions v. TAU (n=74)

≥50% reduction in MADRS

-88

1NNT calculated from reported categorical response/remission rates rather than ES, as per Furukawa TA, Leucht S (2011) How to Obtain NNT from Cohen’s d: Comparison of Two Methods. PLoS ONE 6(4): 19070.doi:10.1371/journal.pone.0019070

Summary

• Some low intensity comparators (TAU/UC) have advantage of comparing IPT to “real world” conditions

• Many disadvantages to this model (ethical concerns, lack of control for nonspecific factors of both clinical trial itself and psychotherapy, variability and lack of measurement of intervention)

• Yields large effect sizes