Hypothesis and objectives
We expect that patients in the IST group will reattempt suicide at an earlier date and a higher frequency as compared to patients enrolled in the GPACTS. The primary objective of this study is to evaluate the efficacy of a program of 6 sessions of GPACTS (as compared to 6 sessions of IST) designed for preventing repeat suicide attempts at 12 months post-psychotherapy in adults admitted to inpatient care for suicide attempts. The secondary objectives of this study are to assess the efficacy of GPACTS on: parameters describing the incidence of suicide and repeat suicide attempts, as well as suicide reattempt free follow-up time long-term changes in suicidal ideation, long-term changes in psychiatric symptoms (depression, hope for the future, hospitalization).
Study setting and design
The clinical aspects of this trial will take place within participating in academic or private hospitals (urban setting) located in France. Eight centres (seven academics and one private) have agreed to participate. This is a multicentre, parallel group, randomized (1:1 ratio), two-tailed-superiority trial with endpoint-assessor blinding. Patients meeting inclusion criteria during a screening visit will be enrolled in the study and randomized into two groups: one group will undergo six weeks of IST (the control group) and the second group will undergo six weeks of GPACTS (the experimental group). Randomization will be carried out by a designated person, who is not a follow-up assessor, following baseline assessments.
Interventional therapies will take place once per week for six weeks in appropriate facilities at the participating centres. The psychologists in charge of interventional therapies will be trained prior to study start in order to homogenize practices between participating centres. The psychologists in charge of group therapy are not the same as those in charge of individual therapy (to help avoid cross-contamination between arms); pre-study training is similarly separated by therapy type (i.e. a participating psychologist is trained in only one type of psychotherapy, which he/she administers during the study). We used the Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) Statement [13] to prepare the protocol manuscript. A SPIRIT diagram for enrolment, interventions, and assessments is shown in Fig. 1 and the SPIRIT 2013 cheklist is shown as additional file 1.
Outcomes and characterization of the sample
Following six weeks of interventional therapy, patients are followed-up for 12 months. Follow-up for both groups is identical and includes the administration of questionnaires at baseline and then within 10 days after the end of GPACTS/IST sessions and then at 3, 6 and 12 months following the end of GPACTS/IST sessions. The primary outcome of interest for this study is the duration of time free of suicide re-attempts. The null hypothesis for the primary outcomes for this study is that there will no significant differences in the duration of a suicide re-attempt-free follow-up period between the intervention and the control group.
Several secondary outcomes will be evaluated:
- The Columbia Suicide Severity Rating Scale (C-SSRS). This physician-administered scale prospectively measures the severity and intensity of suicidal ideation, the different types of suicidal behaviour and the lethality of suicide attempts [14]
- The Beck Scale for Suicide Ideation (BSSI) is a 21-item, validated, self-report questionnaire that can be used to identify the presence and severity of suicidal ideation [15,16]
- The Beck Depression Inventory (BDI-II) is a self-assessment scale. Its purpose is to quantify the intensity of depression [17]
- The Beck Hopelessness Scale (BHS) is a validated questionnaire designed to measure an individual’s expectations about the future [18,19]
- The Mini International Neuropsychiatric Interview – 7 (MINI) is a tool that helps identify the psychopathology of a subject according to the DSM5 [20]
- The Risk rescue rating scale (RRRS) assesses the lethality of a suicide attempt, defined as the probability of inflicting irreversible damage. The underlying hypothesis is that lethality can be expressed as a ratio of factors influencing risk and rescue [20]
- Demographic forms and other assessments are used to characterize the sample and control for potential confounders.
These additional scales provide valid appraisals of factors related to suicidal behavior such as:
- Life events: the Social Readjustment Rating Scale (SRRS, [21]), the Childhood Experience of Care and Abuse Questionnaire (CECA-Q, [22])
- Personality traits: Spielberger's State-Trait Anger Expression Inventory (Staxi-2, [23]), Barratt Impulsiveness Scale (BIS11, [24]), State-Trait Anxiety Inventory (STAI, [25])
- Cognitive functioning : the Cognitive Reflection Test (MIT-IQ, [26])
- Severity of alcohol and tobacco dependence : the CAGE Questionnaire [27] and the Fagerström questionnaires [28]
Ethics, consent, and permissions
The study design is reported in line with the Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT, [13]). The study has received ethical approval from the University Medical Division Ethics Committee, Nîmes, France (#1994798 v0). All patients participating in the study will provide informed signed consent.
Eligibility criteria
Participant inclusion criteria:
- has given his/her informed and signed a consent
- must be insured or beneficiary of a health insurance plan
- is 18 years of age or older
- speaks fluent French
- is freely hospitalized (in centres or via emergency services) for the prevention of suicide
- has a high suicide risk score according to a MINI structured interview
- prior (or recent) suicide attempt within the last month
- is able to understand the study and capable of giving his/her informed consent
- is available during the weekly time slots proposed by the investigator
Participant exclusion criteria:
- is participating in another interventional study, or has participated in another
interventional study within the past 3 months
- is in an exclusion period determined by a previous study
- is under judicial protection, or is an adult under guardianship
- is impossible to correctly inform the patient, or the patient refuses to sign the consent
- emergency situations preventing proper study conduct
- history of schizophrenia or other psychotic trouble
- presence of psychotic symptoms at the initial interview
- serious cognitive impairment
- medical incapacity to participate
- severe dependence on any substance (including alcohol and cannabis) according to the MINI
- current psychotherapy
Interventions
Description of individual supportive therapy
In the comparator group, the “intervention” corresponds to six 60-90 minutes IST sessions administered for 6 weeks (with one session per week). IST does not rely on specific theories or assumptions about the causes of suicide. IST will be focused on the patients’ daily life experiences. The role of the psychologist will be to structure the interview and its duration. However, with respect to specific processes related to the modification of suicidal beliefs, IST is not a specific treatment, and the strategies from cognitive and behavioural approach will not be used in any way.
Description of cognitive behavioural group therapy
In the experimental group, the “intervention” corresponds to six 90-120 minutes group cognitive therapy sessions administered for 6 weeks (with one session per week and 6 persons per group). Sessions must start within 8 weeks after the inclusion date for every patient.
The protocol was adapted from individual face-to-face therapy as described by Ghahramanlou-Holloway et al. [29,30] for preventing repeat suicide attempts and known as Post-Admission Cognitive Therapy (PACT). In reference to this work, we named our program GPACTS.
PACT was also adapted by the authors from a 10-session CBT program developed by Brown et al. [31] to prevent repeat suicide attempts. As pointed by the authors, PACT is based on Beck's theories of depression [32,33] and suicide [31] and serves as a foundation for GPACTS.
GPACTS will consist of six sessions with the same overall therapeutic goals identified by Ghahramanlou-Holloway et al. [29]: 1) to reduce suicidal recidivism, 2) to reduce the impact of psychological risk factors such as depression, chronic suicide ideation, and hopelessness, 3) to develop problem-solving skills and coping strategies by linking them to the problems that contributed to the suicidal act, 4) to develop the use of existing social support, 5) to improve the use of and the collaboration with mental health professionals, and 6) to help the patients in developing a safety plan including coping strategies to preventing relapse.
All GPACTS group session will be structured as follows: 1) Welcome and introduction to the agenda of the session, 2) Summarize the previous session and correction of exercises performed at home, 3) Work on today's theme (e.g. learning problem-solving techniques), 4) Presentation of exercises to do at home, and 5) Feedback from participants on the meeting and answering questions.
The six sessions are distributed in three modules as follow:
- Module 1 is called “Understanding” and consisting of sessions 1 and 2. Session 1 provides general information about the program, introduction to CBT and provide psychoeducation about the suicidal crisis. Session 2 is focused on collaboratively generating a cognitive and behavioural conceptualization based on a narrative review of the most recent suicide attempt.
- Module 2 is called “Mastering” and consisting of sessions 3, 4 and 5. In the session 3, the problem of hopelessness is introduced through the identification of personal reasons for living and the purpose of constructing a hope box containing different elements (such as letters from friends, coping strategies cards, pictures… ). The objective of a hope box is to have tangible evidence that life is valuable and make the reasons for living concrete. Session 4 is focused on the impact of low emotional regulation and its contribution to the recent suicide attempt. The need to improve the coping strategies is introduced through teaching and practice progressive muscle relaxation and controlled breathing exercises. In session 5, the patients are introduced to the relationship between problem-solving deficit and suicidal crisis. The patients are invited to identify from their cognitive and behavioural conceptualization for their recent suicide attempts their personal problem-solving style. The classic steps of problem-solving will be reviewed with the patients: 1) identifying problems and emotions related 2) generating solutions, 4) weighing pros and cons of solutions, 5) choosing the most realistic solution, 6) carrying out the solution and assessing its outcome.
- Module 3 is called “Preventing”, consisting of session 6. This session is focused on relapse prevention and the construction of the safety plan. In order to prevent relapse, patients are asked from the most recent suicide attempt conceptualization, to imagine how the different strategies learned during GPACTS could influence positively the crisis unfold. Finally, a safety plan is individually constructed using an adaptation of the model presented by Stanley et al. [34]. In this form, patients are invited to develop a personal and hierarchically list coping strategies to use in future distressing situations.
Treatment integrity
The coordinating psychologist will visit each participating center to present the interventional therapies and homogenize practice between centres. In each participating center, the psychologists will be instructed about one of the interventional therapies (GPACTS or IST) and will receive a treatment manual. This treatment-manual will be used during the treatment to help the psychologists to stay focused on interventional therapies.
Sample size and recruitment
We will test the following hypothesis: The mean time to the next suicide attempt during the follow-up period is different between the two groups. The probability of a suicide reattempt-free follow-up period (PSRFFP) according to usual care was estimated at 60% by Brown et al. [7]. In this trial, a cognitive-behavioural therapy (10 sessions of individual therapy) was associated with an increase of 20% in the PSRFFP at 12 months.
In our study, the 10 sessions of individual therapy program are replaced by 6 sessions of a group therapy program. We expect a minimum benefit of 20% for this new strategy (60% in the control group versus 80% in the experimental group).
To our knowledge, no study has reported intra-class correlation coefficients associated with therapists or group therapy suicide re-attempt of the C-SSRS score. It is therefore difficult to anticipate an exact sample size that would take into account clustering effects caused by group therapy (or by therapist effects) in the primary outcome assessment.
Under the hypothesis of no cluster effects (at either the therapist or therapy-group levels) and using a log-rank-test, 186 subjects are required to detect 20% difference in PSRFFP at 12 months (60% in the control group and 80% in the experimental group), with a power of 85% and a bilateral alpha risk of 5%.
Given the possibility of cluster effects, we have increased this number to 216. Taking into account an anticipated rate of 10% lost of follow-up, 240 patients will be included (120 patients per group).
Patient consulting under emergencies for suicidal behaviour are common. It is more than reasonable to expect at least one case per day per centre on average, giving a minimum potential patient pool of about 1460 patients during the proposed recruitment period. To take into account the time necessary to organize group sessions and the probability that some patients might not want to participate, we proposed an inclusion averaging 5 patients per month per centre.
Study Calendar
The maximum study duration (i.e. starting at enrolment and ending at close-out) for a given patient is 15.5 months. The anticipated study calendar provides for 12 months of inclusion, 15 months of follow-up, 6 months of data management, and 6 months of statistical analysis and reports writing.
Statistical analysis
The statistical analysis will be performed by the Department of Biostatistics, Epidemiology, Public Health, and Health Economics of Nîmes Hospital Center using SAS statistical software, Carey, NC. A difference will be considered as statistically significant if the test gives a p-value of 0.05 or less.
Description of the population included and main parameters studied
Initial data analysis will describe the total population and the population per group. The Shapiro-Wilks test will be used to determine whether or not the quantitative variables show a normal distribution. Statistical results will be presented in the form of “mean ± standard deviation" for quantitative variables showing a normal distribution, and "median and interquartile intervals" for other variables. The number and associated percentage will be given for qualitative variables.
Analysis of the principal endpoints
The duration of a suicide reattempt-free follow-up period (SRFFP) will be assessed in the two groups using the Kaplan Meier method and compared by a log-rank test. This analysis will be completed by a modeling analysis to take into account clustering effects.
Indeed, in our study, randomization to treatment is done on an individual basis. However, the experimental treatment is administered to a group so that several individuals receive the intervention together by the same therapist. Observations within the group therapy will likely be correlated within groups (clustering effect). In contrast, control participants receive an individual intervention and their observations can reasonably be assumed to be independent. Either arm may also be influenced by cluster effects linked to a particular therapist. The latter clustering results in asymmetric, partially nested designs. Recently, statistical models were developed to appropriately evaluate treatment effects when using a partially nested design [35]. Based on these, we will use multilevel mixed-effects models to assess the treatment effect on the outcomes describing the suicidality:
- The duration of a suicide reattempt-free follow-up period (SRFFP),
- The suicide reattempt during the follow-up (yes/no) by adjusting for nested effects,
- The C-SSRS Score at 12 months by adjusting for nested effects and C-SSRS score at inclusion.
The detailed statistical plan will be provided before data extraction and un-blinding.
The models will also provide valuable estimates of intracluster correlation coefficients for the different psychological outcomes of our study in the context of behavioural group therapy; these data are necessary to optimize the sample size of further studies in the area of psychological research.
Analysis of the secondary endpoints
Multilevel mixed-effects models will be used to assess treatment effects on the evolution of the C-SSRS score and the suicidal ideation (BSSI Score) and of the psychiatric symptoms (BDI-II, BHS).
Guess-the-group
To control for the success of blinding, outcomes assessor responses to the “guess-the-group” question will be compared to true responses using the Kappa agreement coefficient.
Methods used to manage data that are missing, unused or invalid
For the primary analysis, the data are censored for the primary outcomes (SRFFP); it is not relevant to replace missing values. For the other outcomes, we do not have a replacement method for missing data.
Choice of patients to be included in the analyses
All patients included and randomized in the study will also be included in the analysis (intent-to-treat analysis). The conclusions of the study will be based on this analysis. Exploratory Per protocol analysis will be also performed.