Comparative Effectiveness Research in Veterans With PTSD

VA Cooperative Study CSP #591 is designed to compare the effectiveness of Prolonged Exposure
and Cognitive Processing Therapy for treating posttraumatic stress disorder (PTSD) in male
and female Veterans. PTSD is a serious and prevalent condition in Veterans, affecting just
under 9% of VA patients in FY11. Since 2005, the number of VA patients with PTSD has
increased 14.8% annually, due not only to new Veterans but also to increased numbers of
Vietnam Veterans who are seeking care. In FY11, PTSD was the 3rd most common
service-connected disability in VA.

Despite solid evidence that Prolonged Exposure and Cognitive Processing Therapy are effective
treatments for PTSD in Veterans and non-Veterans, there is insufficient evidence about the
effectiveness of these treatments relative to one another. The only study to compare the
treatments, a single-site trial in non-Veteran female rape survivors, failed to find a
difference, but the study was not adequately powered to compare two such effective
treatments. Other data are similarly inconclusive. CSP #591 would break new ground as the
first large-scale comparative effectiveness trial of treatment for PTSD and the first study
to provide definitive information about how effective treatments for PTSD compare with one
another.

The study will be a prospective randomized clinical trial with blinded assessment. The
population will be male and female Veterans with PTSD due to any traumatic military event.
Patients who are eligible and agree to participate in the study will be randomly assigned in
a 1:1 ratio to receive Prolonged Exposure or Cognitive Processing Therapy. The investigators
propose to administer 12 weekly sessions of each treatment as a standard "dose" but to allow
participants who improve more rapidly to finish in 10 or 11 sessions and participants who
have not attained adequate improvement by session 12 to have up to 2 additional sessions.

The primary outcome is improvement in PTSD symptom severity as measured by change on the
Clinician-Administered PTSD Scale after treatment. The outcome measure will be determined
from regular follow-up visits of the patients, which will occur at the middle and at the end
of treatment and then 3 and 6 months later. Secondary outcomes include other measures of
PTSD, comorbid mental health problems, functioning, quality of life, and service utilization.
The investigators also will measure participants' treatment preference and examine whether
concordance between preference and allocation is associated with increased treatment
effectiveness.

In order to detect a standardized mean difference in improvement in PTSD symptom severity of
d = .25, a sample size of 900 randomized patients provides 90% power to detect a difference
between arms using the linear mixed effects model with a two-sided = .05. Given the lack of
conclusive findings to predict which treatment is better, the investigators propose to test a
nondirectional hypothesis. Assuming 2.5 years of accrual and an enrollment of 26 participants
per year at each site, the investigators would need 14.1 sites to enroll a total of 64
participants per site. The investigators propose to recruit 17 sites to guard against the
possibility that some sites will not enroll the required number of participants.

VA has a vested interest in understanding the relative effectiveness of Prolonged Exposure
and Cognitive Processing Therapy. Both treatments are recommended at the highest level in the
VA/DoD PTSD Practice Guideline. VA is required to make these treatments available to Veterans
seeking PTSD care. The treatments are being disseminated nationally across the VA system in
order to enhance the availability of evidence-based treatments to Veterans with PTSD. VA also
has developed a national PTSD Mentoring Program for PTSD Program Administrators to help them
manage their clinics to permit the delivery of these treatments. Every facility has an
evidence-based therapy coordinator as well to facilitate training in evidence-based
psychotherapy.

As a large multi-site trial with men and women, CSP #591 would provide definitive information
about the comparative effectiveness of Prolonged Exposure and Cognitive Processing Therapy
and maximize the study's impact on the field. Because the treatments are based on differing
theories about the development of PTSD, a demonstration that one treatment is superior to the
other would further scientific exploration by challenging theoretical accounts of etiology
and treatment. Regardless of which treatment is better, patients would have more information
to help them make an informed decision about which treatment to choose and VA would have
stronger evidence to help make care Veteran-centered.

Inclusion Criteria:

Current PTSD and symptom severity of 25 or higher on the Clinician- Administered PTSD Scale
(Weathers et al., 2013); agreement to not receive psychotherapy for PTSD during study
treatment and allow digital recording of phone interviews and therapy; regular access to a
telephone (or agreement to come to the VA for centrally conducted telephone interviews for
participant who do not have telephone access). Medication for PTSD and other mental or
physical conditions, psychotherapy for other problems, brief visits with an existing
therapist, and self-help groups will be allowed.

Exclusion Criteria:

- substance dependence not in remission for at least 1 month;

- current psychotic symptoms and mania (including manic phase of bipolar disorder);

- significant current suicidal or homicidal ideation that includes a specific plan;

- or moderate to severe cognitive impairment defined as 1 SD below age-graded norms on
the Montreal Cognitive Assessment.