Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT02895269 |
| Other study ID # |
1U19MH098718-01 |
| Secondary ID |
|
| Status |
Completed |
| Phase |
N/A
|
| First received |
July 30, 2016 |
| Last updated |
December 11, 2017 |
| Start date |
September 2016 |
| Est. completion date |
October 2017 |
Study information
| Verified date |
December 2017 |
| Source |
University of Ibadan |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
COSIMPO is a randomised controlled trial in which a collaborative shared care for psychosis
implemented by complementary alternative providers (traditional and faith healers) and
conventional primary health care providers (PHCP) is compared with care as usual in which no
formal collaboration takes place between the two groups of health providers. COSIMPO is
therefore a test of a complex task sharing approach for the care of patients with severe
mental disorders.
Description:
Most patients with psychotic disorders receive care from traditional and faith healers
(complementary alternative providers, CAPs) in the setting of COSIMPO (Nigeria, Ghana).
Treatment modalities by the healers include the use of herbs and rituals but may also involve
potentially harmful practices such as shackling and scarification. The objective of COSIMPO
is to compare the effectiveness of a collaborative shared care program between the CAPs and
PHCP in improving the outcome of patients with psychosis under the care of CAPs facilities
compared with that of usual care. A cluster randomized control trial design is implemented in
Nigeria and Ghana. Patients in the control arm receives usual care enhanced through the
training of PHCP in the arm, but no structured or formal collaboration is implemented.
Primary hypothesis: Patients presenting to CAPs facilities engaged in collaborative shared
care with PHCP will have better outcome of psychosis compared to patients in enhanced usual
care at 6 months following entry into the trial as measured by a significant mean reduction
in symptoms as rated with the Positive and Negative Syndrome scale (PANSS). For the purpose
of this study, a 7-point difference on the PANSS total outcome scores between the two groups
will be regarded as a clinically meaningful difference.
Secondary hypotheses:
1. Persons with psychosis receiving treatment from CAPs in the collaborative care program
will be less likely to receive harmful treatment or be subject to human rights abuses
(such as chaining, beating, starving, scarification, isolation, forced and prolonged
fasting) than those receiving care as usual.
2. Persons in the intervention arm will be less likely to experience victimization and
abuse from caregivers. Victimisation is defined as an act or action that exploits or
treats a patient unfairly.
3. The patients in the intervention arm will have significantly less disability than those
in the control arm
4. The providers (both CAPs and PHCPs) in the collaborative care program will have better
attitudes to and knowledge of psychosis than those in the (enhanced) care as usual.
5. Collaborative share care will be more cost effective than usual care. Setting and
location of RCT Nigeria: The study site in Nigeria is Ibadan, one of the largest cities
in Africa. The inhabitants are mostly Yoruba with a mix of religious practices being
prevalent. Ibadan is a cosmopolitan city with five of its eleven local governments
(districts) being urban while the remaining six are rural or semi-urban. The population
of Ibadan as of the last census in 2006 was 1,338,659, (Census 2006). There are on the
average about 10 PHCs in each of the local governments and traditional health practice
facilities are ubiquitous. All eleven local government areas in and around Ibadan are
included in the study
Ghana: The Ashanti Region is located in south Ghana and third largest of 10 administrative
regions. With a population of 3,612,950, the region accounts for 19.1 percent of Ghana's
total population (2010 census) (Awuah-Nyamekye, Samuel, and Paul Sarfo-Mensah, 2012). Seven
districts were selected for the study in Ashanti on the basis of having the size of
population required for the study and being accessible to the research center.
Sampling frame The sampling frame will be all the clusters in the local government areas
(LGAs) or district areas selected for the study. For the purpose of this study, a cluster
will consist of a PHC clinic with its neighboring CAP facilities. That is, a cluster will
have one PHC and neighboring CAP facilities, the number of the latter will be determined by
distance, ease of contact, and administrative considerations. A CAP facility will be linked
to only one PHC but a PHC may have more than one CAP facility linked with it. A PHC as well
as at least one of its neighboring CAP facilities must agree to participate in the trial for
the cluster to be included in the sampling frame before randomization.
Sample size and potential power of the trial: The primary outcome considered is the symptom
severity as assessed with the PANSS score. Based on our previous naturalistic follow-up study
of patients with psychosis undergoing treatment, we estimate that a mean difference of 7.5
units on the total PANSS outcome scores between the two arms will represent a clinically
significant difference (given that a standard deviation of 20 was obtained for the PANSS in
that study). With the target effect size of 0.38, an uninflated sample size of 112 patients
per arm will be required to provide a power of 80% and at an alpha of 0.05. Drawing on the
recruitment profile to the trial so far, we estimate that, over the course of approximately
another 2 months (that is, until end of May 2017), we will be able to recruit an average
total of 6 patients per cluster. To take account of the cluster design, we inflate the
estimated sample size by 1+((k-1)*ICC)) where k is cluster size for analysis and ICC is
intra-cluster correlation coefficient. We have data showing that WHO-DAS, (one of the outcome
tools to be used in the study) has an ICC of 0.02 in primary care settings and we make the
assumption that the ICC for the primary outcome tool, the PANSS, will not be significantly
different. Using the resulting design effect of 1.10, the inflated sample size is 246.4
(224*1.10). With an estimated attrition of 20% at six months (an estimate supported by our
experience with the follow-up efforts so far) we will need to recruit a total of 296
participants. With 51 clusters in the study, an average of 6 subjects per cluster will
adequately permit for this target sample size to be achieved.
Informed consent for participation in the trial: Information on the nature and purpose of the
study will be administered to patients, caregivers and CAPs in the local languages to aid
understanding of the research study. All relevant consent forms will be translated through a
process of iterative back translation to the local languages. The languages spoken in the
catchment areas are Yoruba in Nigeria and Akan-Twi in Ghana. Only participants who are able
to speak either of the local languages will be recruited into the study.
The investigators are particularly mindful of the need to take extra care of these issues in
a multi-site study in which the subjects are otherwise vulnerable individuals. With the
cooperation of the CAPs, measures will be taken to ensure privacy during consenting and
screening of patients at the facilities. For the purposes of confidentiality, records of all
data will be stored in locked files rooms and the keys kept by the site data manager. Only
authourised persons will be allowed to have access to the data. Regular training (during
monthly de-briefing) of research personnel about issues of confidentiality will be conducted
to help prevent staff from violating confidentiality. Data will be stored securely at both
study sites (in Kumasi and Ibadan).
THE COLLABORATIVE SHARED CARE The collaboration between the CAPs and the PHPCs taps into the
skills of both types of care providers in the management of patients with psychosis. The
patients that will be treated in this collaborative effort will have access to both orthodox
medicine on the one hand and complementary alternative medicine (CAM) on the other hand. It
is important to note that, in the design of COSIMPO, patients belong to the CAPs primarily
and the PHCP acts only in advisory and supportive capacity in patient management. This is
because these patients have presented primarily to the CAPs and, for the most part, are seen
and managed at the CAPs facilities on either an inpatient or outpatient basis. Every aspect
of the col-laboration is therefore designed to enhance the CAP's acceptability through
delivery of better care. The role of the PHCP is to help the CAP to provide safe, acceptable
care to patients, including promotion of and respect for human rights and avoidance of
harmful practices. The PHCP will also assist the CAP in accepting the provision of
evidence-based care to patients, when the PHCP determines that it is indi-cated. This
collaboration should promote mutual respect, trust, support, referral and advice among the
CAPs and PHCPs. Evidence-based medications will be prescribed only by trained health care
person-nel. CAPs in the intervention arm commit themselves to implementing enhanced patient
care through the collaborative arrangement with PHCPs. This commitment is explicitly obtained
from each CAP prior to their inclusion in the trial. In this regard, they agree and commit
themselves to utilizing the arrange-ment to avoid practices that are potentially harmful or
abusive and to engaging with PHCPs for the overall care of patients referred to them. The
frequent visits of the research team will also be used to encourage and reinforce their
commitment. As described in Section 7.2.4, CAPs in the intervention arm who refuse to
implement the collaborative arrangement or persist in the use of harmful/abusive ap-proaches
will be excluded from further participation in the trial.
The entry point to treatment for patients will be from the traditional healers or faith
healers (i.e., CAPs). The CAPs take responsibility for the patient and commence treatment.
The contract to care for the pa-tient therefore lies with the CAP. The discretion about when
to seek clinical support from or refer to the PHCP lies with the CAP. The PHCP in turn
provides the necessary support and assistance needed. In providing clinical support to the
CAP, the PHCP may engage with the CAP, the patient, and caregivers of the patient. Beyond
specific referrals and consultations, the PHCP will maintain regular weekly scheduled
personal contacts with the CAPs as part of the collaboration, using such contacts to
reinforce information on best clinical practice, provide information on patient
rehabilitation, and attend to other clinical issues that the CAPs may bring to the attention
of the PHCP.
Main components of the collaborative shared care
The main components of the collaborative shared care can be grouped into two:
1. Clinical support to respond to the medical need of psychotic patients: This involves the
provision of medical care to patients, especially those in conditions of acute psychotic
disturbance, by PHCP following the request from CAP.
2. Clinical support to improve service on a continuous basis: This involves engagement and
inter-actions between PHCP and CAP during which the former provides the latter with
specific in-formation to improve service, organize rehabilitation for their patients,
and generally provide better care. This interaction will involve the provision of
specific information by the PHCP to CAP on scheduled and regular visits and with full
documentation.
These two activities, as now further described, will form the basis of the evaluation of the
collaborative care both in regard to the fidelity of its implementation as well as its impact
or effectiveness.
Clinical support to respond to the medical need of psychotic patients Intervention will be
delivered collaboratively by providers in the intervention arm (CAPs and PHCPs) The
intervention is presumed to start from the time TP consents to participate in the study until
discharged from treatment (by either the CAP or PHCP). (Patients who enter the study are
monitored and evaluated for outcome until the end of the primary outcome at six months
irrespective of whether they have been discharged from treatment earlier). Intervention is
initiated at the CAP facility but may subsequently involve the PHCP facility or other medical
facility, depending on whether the patient is referred to any such other facility or not and
based on the agreement between the CAP and the PHCP. It will consist of the treatment
modalities as determined by the CAP and by the PHCP when called by the CAP or during routine
engagement visits to the CAP. That is, all eligible and consenting patients who are recruited
to the intervention arm of COSIMPO will have their treatments initiated by the CAP to whom
they have presented. Some will continue with such treatments if the CAP does not seek the
input of the PHCP in the care of the patients. Some other patients for whom the CAP seeks the
input of the PHCP will receive treatments as prescribed by the PHCP in addition to whatever
treatments the CAP is also offering to them.
When a PHCP is involved in the care of a particular patient, the PHCP assesses the patient at
the CAP facility, provides feedback to the CAP, and initiates treatment according to the
Mental Health Gap Action Programme Intervention Guide (mhGAP-IG). The PHCP continues to
monitor the patient by regular visit to be determined by clinical need of patient (for
example, administration of specific medications may require dai-ly or more visits to monitor
their effects). If the patient is on herbal medication, PHCP takes this into con-sideration
in administering medication. PHCP may refer patient to see a physician or specialist, if
judged necessary, and in consultation with the CAP.
Specified reasons for consultations of PHCPs by CAPs
Based on information derived from our formative studies, COSIMPO will specify the following
specific reasons for the healer to consult the PHCP:
- Very disturbed, agitated or aggressive patients
- Patients at risk of absconding
- Patients at risk of self-harm or harm to others
- Patients who have side effects of medication
- Patients who are not getting better despite efforts by the healer
- Patients who have other comorbid physical conditions, such as fever, injuries, breathing
dif-ficulties (breathlessness), severe throbbing headaches, urinating excessively either
during the day or at night, drinking water excessively, previously diagnosed
hypertensive and or diabetics or any other condition that requires medical attention.
Care by the PHCP Once a PHCP is consulted by a CAP for assistance in the care of a patient,
the PHCP will follow the guidelines for the management of patients with psychosis as laid
down in the mhGAP-Intervention Guide in figures 11 and 12 below. The provider will conduct
assessment and offer treatment according to the procedures in the Guide and as adapted for
COSIMPO. Referral to other levels of care, when needed and dictated by the Guide, will be
decided by the PHCP but implemented with the approval of the CAP. The PHCP will keep a record
of all interactions and treatments in patients' records note books provided by COSIMPO
research team to be kept at the PHC facility where the PHCP is based. The records will be in
form of patient clinical narrative entries as typically collected by the PHCPs, but
supplemented with specific forms and checklists that capture the activities included in the
collaborative care program, designed for COSIMPO, and in the form that can be abstracted into
the study data base. The checklist will include de-tails including date, time, and duration
of visit; psychosocial advice or intervention provided; counseling on harm reduction given;
perceived receptiveness and cooperativeness of the CAPs. Space will be provided for writing
detailed notes on the experience of the visit including suggestions to improve the
collaboration.
Duration of treatment period and follow-up This research project is not imposing a specific
treatment duration period. PHC workers and CAPs are free to select the treatment and duration
in line with usual standard practice, and may or may not be influenced by the guidelines in
the collaborative shared care package. Thus, all clients attending primary care clinics and
CAPs will receive usual treatments, in line with routine standard practice, and may or may
not be influenced by the guidelines in the collaborative shared care, or whatever duration is
prescribed by the PHCP worker or the CAP. However, primary outcome will be assessed at 6
months following entry into the study, irrespective of whether the patient is still in
treatment or not.
Instruments
The following instruments will be used for baseline and outcome assessments:
The Structured Clinical Interview for DSM-IV Axis disorder Positive and Negative Syndrome
Scale (PANSS) World Health Organization's Disability Assessment Schedule 2.0 (WHODAS 2.0
direct patient version and PROXY VERSION) Internalized Stigma of Mental Illness Life Chart
Schedule (LCS) Service Utilization Questionnaire
Checklist of harmful practices by CAPs:
Knowledge about Schizophrenia Interview (KASI)
Checklist of victimization and abuse by caregivers:
Family Burden Interview Schedule
Blinding: TPs will not be blinded to the patients' treatment arms (as it is impossible to
conceal the fact of collaboration or lack of it from the patients). There shall be two groups
of trained RAs: those conducting the baseline assessment and those conducting the outcome
evaluations. While the former cannot be blind to patient trial arm (given that RA's will
conduct the assessment at the recruitment facility and will get to know about the fact of
collaboration or lack of it), the latter will be kept blind to trial allocations. In view of
the possibility that some patients may still be on admission at the facility (in which
recruitment has occurred) at the 3-month assessment point, it may be difficult to conduct
this particular assessment blind by the RAs. However, the main outcome measures (at 6 month)
will be administered by outcome assessors (RAs) independent of the intervention and blind to
the allocation of treatment. TPs will be instructed not to disclose details of care being
received to the outcome assessors. The primary outcome measure (PANSS) will always be
completed first in order to minimize the risk of bias in the event of unmasking during the
assessments and, if it occurs, the point of unmasking will be recorded. Sensitivity analyses
will be carried out to assess the effect of unmasking on the primary outcomes. The
intervention and outcome assessment teams will not have any interactions during the trial and
will have separate physical location and administrative management. Table 13 shows a summary
of blinding and treatment allocation of the COSIMPO team member.
Risks and potential discomforts in COSIMPO Human Subjects Protection Procedures for human
subjects' protection in this research will follow guidelines and policies of the
Institutional Reviews Boards (IRBs)-- of the sponsoring organization, the University College
Hospital/University of Ibadan, ethical review board and the College of Health Science,
Nkrumah, Ghana and the NIMH DSMB. The site investigators have completed Human Participant
Protections Education for Research Teams sponsored by National Institutes of Health, U.S.
Department of Health and Human Services.
Definition of Adverse Events (AE) Even though the possibility of adverse events, which are
directly related to the intervention is low, a critical incident register will be maintained
during the study to record specific serious adverse events (SAEs) and Other Adverse Events
(OAEs).
SAEs include:
Death, due to any cause Any suicide attempt Any violence towards others Harmful or abusive
treatment practice Victimization (violence against the TP) Hospital admission due to
psychiatric problem Hospital admission due to serious medical emergency Incarceration Events
that may require extraordinary response, such as high risk of suicide attempt, or rapid and
severe clinical deterioration Stigmatization (due to the intervention) Sexual abuse,
including rape An event or finding with the potential to become an international incident
Other Adverse Events (OAEs)
Other adverse events (AE), which are any other medical occurrence trial patient which does
not necessarily have a causal relationship with this treatment, will be identified. This may
include any of the following:
1. Clinically significant problems not requiring hospitalization or extraordinary response
2. Onset or worsening of medical problems not requiring hospitalization
3. Other events that do not meet criteria for serious adverse events, for example, a report
of suicidal ideation without risk of a suicide attempt Other foreseeable
risks/discomforts and mitigation strategies This research study has little risks and
discomforts. However foreseeable risks associated with the COSIMPO trial will be
described to every prospective subject as part of standard information before consent is
provided. Also steps to mitigate such risks for every subject category by the research
team would be described to the different category of subjects as applicable.
Response to SAEs When a RA detects SAEs, the required information below will be collected
systematically on tablets (electronic data collection) during the outcome assessments. In
addition such will be immediately reported to the research supervisor who will in turn report
to the trial management, who will them immediately inform the PI all within 24 hours. Also
the information on the SAE will be uploaded daily to the database and the DM will complete
the first part of the SAE report and bring such information to the attention of the trial
manager.
Information required for reporting adverse events
Data collection: Interviews will be conducted at baseline, 3,and 6 months. The questionnaires
will be administered by trained research assistants (RA). Data will be collected directly
using tablet computers and uploaded to a remote server by the data manager every two days.
Three types of data will be collected:
1. Baseline data
2. Follow-up outcome data
3. Process data For all data, range and consistency checks will be performed at weekly
intervals separately for each data source and, where relevant, consistency checks will
be carried out. Any queries identified will be resolved promptly by the data management
team, and the database will be updated, maintaining the audit trial. All data will be
kept in separate databases and only merged into a master database after data collection
is completed and each individual database is 'locked.' Access to data will be password
protected at multiple levels and no member of the trial team apart from the data manager
will have access to these passwords. The database will be backed up daily on a password
protected computer after upload.
Data quality and security of data The site data manager will protect the confidentiality of
personal data principally through procedures to separate study data and participant
identifiable data. These identifier data will be stored electronically in a
password-protected folder and hard copies of the consent form will be stored in a locked
cupboard with access only to the data manager and the site PI. All subsequent data will be
collected and collated using only the trial ID number. Regarding the qualitative data set
that will be collected during process evaluation, participant audio files will be stored in a
password-protected folder and transcribed data will be anonymized with only participant ID
information.
Data Coordinating Centre (DCC) An anonymized and password protected dataset will be
transferred from Ghana to UI to the off site server via the internet. Only trial managers in
both sites would have access to the data during the period of data collection. All DCC
procedures, including reporting to the DSMB, will be overseen by DCC coordinator and Hub
Administrator. Study statistician, supported by the statistical consultant, will conduct
statistical analyses of data and will provide any other statistical advice as requested.
Data and safety monitoring
The NIMH Global DSMB will ensure the safety of TPs. The board will review and approve the
study protocol, informed consent and all relevant documents. The main responsibilities of the
DSMB are, but not limited to, the following:
Review of protocols, consent procedures, consent forms, and safety plans prior to the
initiation of the study; Monitoring of the progress of the study, including recruitment and
retention of participants, adverse events, serious adverse events (SAEs), reasons for
participant withdrawal, adherence to the timeline of the study, quality of data, and protocol
violations; Make definitive and authoritative decisions about the continuation, modification,
or termination of the study, based on the balance of adverse events and beneficial outcomes.
The data and safety monitoring plan will involve the continuous evaluation of safety, data
quality and data timeliness. The PI will be expected to continuously review data and patient
safety which will be reported at TMC and TSC meetings and all discussions will be documented.
The PI will also submit twice yearly progress report to the NIMH DSMB.
-All paper data files (quantitative and qualitative) will be stored in lock and key cabinets
and the computerized data will be password protected. Any back-ups made of the computerized
data will be put on separate hard drives which will also be password protected. Only named
research staff (AR, SS and the data manager) will have access to the data onsite.
Contamination Contamination will be minimized through the geographical spread of the
randomized clusters which will make the possibility of patients moving from a control to an
intervention CAP facility unlikely and also by not publicizing the availability of the
collaboration in the intervention arm to other CAPs.
Statistical analyses Descriptive analyses Initial analyses will compare baseline
characteristics of individuals who consented and did not consent and participants who could
and could not complete baseline assessments, and a comparison of the distribution of
potential confounding factors. Findings will be reported as per CONSORT guidelines for
cluster randomized controlled trials (Campbell, Marion K., Diana R. Elbourne, and Douglas G.
Altman, 2004) including a trial flow chart. This will include the flow of clusters and
participants through each stage of the trial, including the number eligible, randomly
assigned, receiving the intended treatment, completing the study protocol and analyzed for
the primary outcome.
The outcome measures will be summarized at baseline, 3 month, and 6 month follow-ups by
intervention arm and overall. These will be summarized by means (SD), medians (IQR) or
numbers and proportions as appropriate (and including age, gender, baseline outcome score),
adjusting for cluster. For continuous outcomes, histograms within each arm will be plotted in
order to assess how closely the scales follow a normal distribution to determine how to
describe the outcomes and how to properly do the inferential analysis. The clusters will be
described in terms of gender, education, country site, and profile of the CAPs (e.g., small
vs. large).
Outcome analyses The primary analyses will be intention-to-treat at the 6-month follow-up
visit adjusted for baseline measures. That is, after randomization, patients will be analyzed
according to study arm allocation irrespective of the treatment being actually received.
These analyses will also disregard adherence to the intervention or withdrawal from the
trial. Random-effects logistic regression will be used to analyze binary outcomes, adjusting
for country site and cluster size as random-effects variables. Analyses of continuous
outcomes will use random-effects linear regression, additionally adjusting for the baseline
value of that outcome. Adjustments will also be made for any of a-priori defined set of
potential confounding variables for which randomization did not achieve balance between the
two arms at baseline.
Missing data The number (%) with complete data will be reported. In instances where the
methods for dealing with missing data have been recommended in the scales, these will be
used. When no such recommendations are available, the investigators will employ multiple
imputations and a fully conditional model based on Markov Chain Monte Carlo (MCMC). Imputed
data will be used in secondary analysis.
