The local landscape
The Australian experience has been one of a steep learning curve; however the development of local experience and expertise has been supported by enthusiastic clinicians and international networks including TREAT-NMD and CINRG.
Our aim should be to consolidate a clinical trials network involving centres in the major sites in Australia and New Zealand, such that all patients have access as trials come on-line. Clinical trials in leukaemia provide an excellent model of the role of clinical trials to improve patient survival. The childhood leukaemia survival rate in the 1970’s was approx. 25%. Since that time treatment for every patient has been provided as part of clinical trials. In 2009 the survival rate was 92% – demonstrating the efficacy of a coordinated approach.
The recent PTC124 (Ataluren) trial was undertaken across two Australian sites. The extension to this trial was discontinued because of lack of demonstrable efficacy in the primary endpoint on the primary PTC124 trial. Post-hoc subgroup analysis is continuing, but at this point all PTC124 trials in DMD and BMD have been halted. Although this was a disappointing outcome, there were a number of positive outcomes from the Australian participation in this trial. One very positive outcome is that Australia is now considered along with the US, UK and Europe as a viable first line site in which to conduct clinical trials. The study increased local expertise and demonstrated that definitive results for trials of potential new treatments for DMD can be very quickly obtained through well-run international multicentre studies.
The experience with PTC and CINRG has also provided insight into the infrastructure required to run effective, well-designed clinical trials.
- A principle investigator (physician) and two backup clinicians so that medical staff are always available for initial and follow-up appointments and to be on call at all times to manage possible adverse events.
- A clinical trials coordinator for organisation of ethics approval/data management/data entry/reporting of results/organisation of phone conferences/appointments/labs/audits and sending away of specimens etc. In addition the clinical trials coordinator organises patient visits and appointments.
- At least two trained evaluators (one as backup when the other is not available)
- Experienced and cooperative surgeon to do muscle biopsies and someone to follow up processing and sending of specimens
- A blood collector to take bloods in a timely fashion
- Laboratory staff available to process specimens in a timely and fastidious fashion and to send them away for analysis
- On –site Clinical Trials Pharmacist
An overseas model
TREAT-NMD has a database of approx. 200 potential trial sites containing a substantial amount of feasibility information relating to available services, expertise and equipment. As queries are received relating to potential clinical trials, sites and registers/patient numbers are mapped against the details of the trial to determine the most appropriate centres to run each trial. . As the Australian network of sites is developed, TREAT-NMD would welcome registrations from each and every site that sees a substantial number of neuromuscular patients or is interested in being part of future trials.
In order to attract more clinical trials to Australia, we need to build a coordinated clinical trial infrastructure. Clinical trials also provide the opportunity to make the latest in therapies available to patients in Australia. Companies look at patient numbers, expertise and experience in potential trial sites. The existing local experience and expertise provides an opportunity to train personnel to staff additional trial centres around Australia. This will simplify the onerous travelling requirements for many families.
The proposed model would involve representation from each state within the Australia/New Zealand Neuromuscular Network. As trial opportunities arise through TREAT-NMD, CINRG and other organisations, information regarding potential sites in Australia, patient cohorts and expertise will be readily available.