VIFM ETHICS COMMITTEE
FINAL REPORT FORM FOR RESEARCHERS
Section 1 - Information for researchers
Annual reports are to be:
- signed by the Principal Researcher
- submitted on the anniversary of the VIFM Ethics Committee approval each year until a Final Report is submitted
- emailed and sent to the Executive Officer of the VIFM Ethics Committee:
Ms Fiona Leahy
Executive Officer, VIFM Ethics Committee
57-83 Kavanagh Street
Southbank VIC 3006
Section 2 – Project Details
1.Project number (e.g. EC 13/2009)
EC 12/20072.Full title of project
A case-control study to identify risk factors for myocarditis with clozapine3.Principal Researcher
Professor John Mc Neil4.Organisation/Institution
Department of Epidemiology and Preventive Medicine, Monash University5.Annual Report number (e.g. 1st Report, 2nd Report etc)
4th and final Report6.Expected completion date
31 Dec 2011
7.Summary of the nature of the project
The study is a case-control study designed to identify risk factors, including a genetic marker, for the development of myocarditis with clozapine. Clozapine is the most effective drug available for the treatment of schizophrenia, but it is associated with a risk of myocarditis(inflammation of the heart muscle and a hypersensitivity reaction), usually occurring in week 3 of therapy.
The genetic analysis will focus on the HLA region (where single nucleotide poly- morphisms predisposing to hypersensitivity reactions have been found).
Our expectation is that the results of the study will lead to genetic screening prior to initiation of clozapine, so that those at risk of myocarditis can be excluded from use and the drug used safely and confidently in other individuals. Thus clozapine will be more widely prescribed.
Section 3 – Project conduct1.Has the project commenced?
Yes No Abandoned
2.What date did the project commence?
Overall project commenced 1 Sep 2006. At VIFM, it started Oct 2010.3.If the approval was subject to certain conditions, have these conditions been met?
Yes No
If no, please give reasons.
4.Data analysis
None Proceeding Complete
5.Have problems been encountered in the following areas?
Study designYes No
EthicsYes No
Recruitment of participants or donorsYes No
FinanceYesNo
Facilities or equipmentYes No
If yes, please provide details
6.Has the original protocol been modified?
Yes No
7.If Yes, have all modifications been notified to the Committee?
Yes No
Please summarise any modifications to the protocol that have not been notified to the Committee. Please include the number of amendments, a summary of substantial changes to the protocol or the Plain English Statement and latest dates and version numbers. For any modifications that have already been notified to the Committee, please give the date of the notification.
8.Have there been any adverse events?
Yes No
If yes, please give details
9.Have there been any complaints?
Yes No
If yes, please give details
10.Have participants withdrawn?
Yes No Not applicable
11.Has approval expired?
YesNo
12.Have the approved procedures for confidentiality and security of data been followed?
Yes No
If not, please give details
13.Please describe the current arrangements for the storage of data
The study database is stored on a secure network which is backed up daily and access to the database is by password.
The spreadsheet containing identifying information and study codes is stored on the same network and is protected by another password.
Consent forms are stored in a locked cabinet in a secure area.
Section 4 – Project Progress
1.Give a brief statement of progress so far
Please include:
- a summary of findings to date
- details of any publications accepted or in press
- details of any presentations given
- whether participants have been informed of the results (where applicable)
Findings
Using the 105 documented cases and 296 documented controls, the case-control analysis for environmental and phenotypic risk factors has been completed, and an article submitted for publication (see below). In summary, the analysis indicated that the risk of myocarditis is increased with increasing rate of clozapine dose titration, increasing age and with concurrent use of sodium valproate.
We have samples from 44 cases and 67 controls for the genetic analysis and DNA has been extracted from the last of the samples (30 Nov 2011).The genetic analysis is yet to be conducted. From VIFM, we obtained samples from 6 cases. For 3 the next of kin gave consent and for the other 3 the HREC gave permission for the samples to be supplied without consent of the next of kin, who could not be contacted.
Articles accepted for publication:
- Ronaldson KJ, Fitzgerald PB, Taylor DJ, McNeil JJ. Observations from eight cases of clozapine rechallenge after development of myocarditis. Correspondence. Journal of Clinical Psychiatry. Accepted 29 Nov 2011
- Ronaldson KJ, Fitzgerald PB, Taylor DJ, McNeil JJ. Continuation of clozapine following mild myocarditis. Correspondence. Aust N Z J Psychiatry Accepted 14 Nov 2011.
Article undergoing review:
- Ronaldson KJ, Fitzgerald PB, Taylor DJ, Topliss DJ, Wolfe R, McNeil JJ. A case-control study of clinical management factors and phenotypic characteristics related to myocarditis with clozapine. Submitted to American Journal of Psychiatry
Section 5 – Principal Researcher Declaration
I confirm that this project is being conducted as originally approved by the VIFM Ethics Committee (subject to any changes subsequently approved) and that all adverse events are reported to the Committee according to the Committee’s guidelines for reporting of adverse events and the National Health and Medical Research Council National Statement on Ethical Conduct in Human Research (2007).
Principal Researcher Signature
Date: