Clinical trials in New Zealand—an update

In 2010 the New Zealand Health Select Committee investigated the clinical trial landscape in order to consider ways to better coordinate nationwide approaches, remove barriers, streamline processes and measure performance.1 Several submissions to the Health Select Committee noted the lack of any routinely collected or reported metrics on clinical trial activity in New Zealand. Information regarding clinical trial activity in New Zealand is scarce with no information published since a previous report by one of the authors in 2005.2Measures of clinical trial activity can facilitate accurate estimates of the economic value of the activity, enable comparisons to be made between levels of trial activity and known areas of disease burden, and identify the impact of policy and process changes. Thus it seems desirable that clinical trial activity be aggregated, if not routinely, then at least with some regularity.No clinical trial can proceed without ethics committee review and the Health and Disability Ethics Committees publish annual reports on their website that list the studies submitted for their consideration. These details, although limited, are generally sufficient to determine whether a study was a clinical trial. The original intent of this investigation was to describe trial activity from 2004, but the reorganisation of ethics committees adversely affected the reporting for that year.Therefore, the aim of this study was to describe clinical trial activity in New Zealand 2005-2009 and estimate compliance to the International Committee of Medical Journal Editors (ICMJE) statements on trials registration.3 4Methods Annual reports from the six Health and Disability Ethics Committees in New Zealand for the years 2005-2009 were downloaded from the Committees website. The reports were handsearched by one of the authors (VC) to identify applications for ethical approval for clinical trials. To be included, trials must have been referred to as phase I, II, III or IV trials; or have contained the key descriptors randomised trial, controlled trial, double blind, placebo or trial in the title; or have been known to the authors to be randomised controlled trials. Pilot studies were only included if they were randomised pilot trials. Where there was uncertainty as to whether an application related to a trial, further information was sought from the applicant or obtained by internet searching. Trials were not included if the application had been declined or withdrawn. The ethics committee reports were independently reviewed by the second author (AJ) to ensure complete data collect. Information was extracted from the reports on the year of application, the committee from which approval was sought, the phase of the trial, the type of intervention, the condition being targeted, the population group sought for the trial, trial registration and the sponsor or funder. Trial registers that met the World Health Organization (WHO) Minimal Registration Data Set were searched either through the WHO International Clinical Trials Registry Platform or by directly accessing the register (clinicaltrials.gov, the Australia New Zealand Clinical Trials Registry or Current Controlled Trials). Early phase trials were those identified as phase I, II or pilot randomised controlled trials. Phase I or II trials need not have used random allocation. Late phase trials were those that self-identified as phase III or IV trials and must have used random allocation. If the phase of the trial was unable to be identified from internet searches or the trial title, it was categorised as late phase. Each trial was assigned to one of 26 condition categories. If a trial fell into two or more categories it was coded according to the greatest perceived contribution to one category. A random sample of 10% of the data extract was independently reviewed by a second author (AJ) to ensure accuracy of content and agreement with condition categorisations. Although agreement was 93%, all condition categorisations were then reviewed by the second author for accuracy and consistency. Results Ethical approval was sought for 900 clinical trials conducted in New Zealand between January 2005 and December 2009. Trial activity increased within the 5-year period: there were 152 trials in 2005, 181 trials in 2006, 183 trials in 2007, 203 trials in 2008 and 181 trials in 2009 (Figure 1) giving an annual average of 180 trials per year. The trials were predominantly late phase (621 trials, 69%, average 124/year) with 279 trials (31%, average 56/year) being described as phase I or phase II clinical trials (61 and 189 respectively) or pilot randomised trials (29). Figure 1. Contribution (cumulative) of early and late phase trials 2005-2009 compared to data from previous report 1998-2003.2 Note data not available for 2004 The multi-region ethics committee received the largest proportion of applications in the 5-year period, with 379 (42%) of trials falling under this committees jurisdiction (table 1). Northern X reviewed 190 applications (21%), Northern Y reviewed 151 applications (17%), Central reviewed 71 applications (8%), Upper South reviewed 61 applications (7%) and Lower South reviewed 48 applications (5%). A similar pattern was evident with both early and late phase trials, which were most frequently reviewed by the multi-region ethics committee (Early: 112, 40%. Late: 267, 43%), followed by the Northern X (Early: 65, 23%. Late: 125, 23%) and Northern Y committees (Early: 44, 16%. Late: 107, 17%). The pattern varied slightly with the Upper South (Early: 29, 10%. Late: 32, 5%), Central (Early: 20, 7%. Late: 51, 8%), and Lower South committees (Early: 9, 3%. Late: 39, 6%). Early phase trials increased from 25% of trial activity in 2005 to 30% of trial activity in 2009, with peak activity in 2008. 758 (84%) trials could be identified as listed on a WHO-compliant trials register, withclinicaltrials.gov being the most frequent site of registration (498, 55%) followed by the Australia and New Zealand Clinical Trials Register (250, 28%). The percentage of trials registered was highest at 88% (134) in 2005, but fell in the following years to 82% (148) in 2006, 84% (154) in 2007, 82% (167) in 2008 and 86% (155) in 2009. 278 (83%) of non-commercial trials and 480 (90%) of commercial trials were registered; the only year non-commercial trials exceeded commercial trials being registered was in 2005 (Table 3). Table 1. Clinical trials by year and phase for each ethics committee Region 2005 N (%) 2006 N (%) 2007 N (%) 2008 N (%) 2009 N (%) Early Late Early Late Early Late Early Late Early Late Multi-region 16 (42) 47 (41) 19 (37) 54 (42) 32 (53) 57 (46) 25 (34) 59 (46) 20 (36) 50 (40) Northern X 7 (18) 33 (29) 12 (23) 22 (17) 16 (27) 23 (19) 17 (23) 23 (18) 13 (24) 24 (19) Northern Y 5 (13) 19 (17) 10 (19) 18 (14) 8 (13) 25 (20) 13 (18) 21 (16) 8 (15) 24 (19) Central 3 (8) 5 (4) 6 (12) 10 (8) 3 (5) 9 (7) 5 (7) 10 (8) 3 (5) 17 (13) Upper South 7 (18) 5 (4) 4 (8) 12 (9) 1 (1) 3 (2) 7 (9) 5 (4) 10 (18) 7 (6) Lower South - 5 (4) 1 (2) 13 (10) - 6 (5) 7 (9) 11 (9) 1 (2) 4 (3) Total 38 (25) 114 (75) 52 (29) 129 (71) 60 (33) 123 (67) 74 (36) 129 (64) 55 (30) 126 (70) 152 181 183 203 181 Table 2. Clinical trials by year approved and condition Variables 2005 N (%) 2006 N (%) 2007 N (%) 2008 N (%) 2009 N (%) Total N (%) Cancer + Cardiovascular ++ Respiratory Gastroenterology Diabetes Neurology Mental health Anaesthesia/pain Haematology (non-cancer) Rheumatology Womens health Ophthalmology Infectious diseases Emergency/critical care General/vascular surgery Orthopaedics Neonatology Dermatology Renal Urology Dental Gerontology Immunology Transplant Other * Unknown 35 (23) 24 (16) 10 (7) 17 (11) 10 (7) 5 (3) 5 (3) 4 (3) 3 (2) 3 (2) 8 (5) 6 (4) 2 (1) 2 (1) 1 (1) 2 (1) 3 (2) 1 (1) - 1 (1) - 2 (1) - 2 (1) 2 (1) 4 (3) 32 (18) 33 (18) 22 (12) 4 (2) 11 (6) 8 (4) 8 (4) 6 (3) 5 (3) 7 (4) 1 (1) 3 (2) 4 (2) 4 (2) 6 (3) 5 (3) 4 (2) 1 (1) - 3 (2) 2 (1) 1 (1) 1 (1) 2 (1) 3 (2) 5 (3) 30 (16) 26 (14) 17 (9) 15 (8) 18 (10) 7 (4) 4 (2) 7 (4) 7 (4) 7 (4) 7 (4) 2 (1) 6 (3) 6 (3) 3 (2) 4 (2) 2 (1) 1 (1) 3 (2) 2 (1) 3 (2)