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| Journal of the New Zealand Medical Association,
20-April-2012, Vol 125 No 1353
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Clinical trials in New Zealand—an
update
Vickie Currie, Andrew Jull
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 2005.2
Measures 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 4
MethodsAnnual 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.
ResultsEthical 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 committee’s 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, with clinicaltrials.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
Table 2. Clinical trials by year approved and
condition
+ Included
haematological cancers; ++ Included cardiac
surgery and interventional cardiology; *
Included herbal, dietary, injury prevention, education, physiotherapy, sports
science, sleep disorder, and health services delivery interventions and other
endocrine diseases.
Table 3. Trial registration, by year, for
non-commercial and commercial trials (excluding 33 trials where sponsorship
could not be determined)
The sponsor could be identified in 867 (96%) trials either
directly from the annual report or from a trials register. 532 (59%) trials were
funded by industry or other private sponsors (commercially sponsored) and 335
(37%) by public research funders, government agencies or research charities. The
largest single commercial contributor to trial activity was Merck with 50 trials
(9% of commercial activity), followed by Roche (48, 9%), GSK (41, 8%) and
Novartis (28, 5%).
The largest single non-commercial sponsor was the Health
Research Council of New Zealand, providing funding for 70 trials (21% of
non-commercial activity). Universities (both New Zealand and overseas
universities) were the sponsor for 41 trials (12%), while district health boards
or other health providers sponsored 37 trials (11%), and government ministries
or other government agencies sponsored 17 trials (5%). The remaining 170 trials
(51% of non-commercial activity) were sponsored by research trusts or charities
within New Zealand and from overseas.
The largest single condition category investigated was
cancer followed by cardiovascular disease (including stroke) and respiratory
diseases (table 2). The target populations recruited were adults in 631 trials
(70%), infants in 29 trials (3%), children in 22 trials (2%) and adolescents in
7 trials (1%).
Ten trials (1%) targeted both children and adolescents,
while 60 trials (7%) allowed all ages entry (20) or had age criteria that
allowed a mix of children, adolescents and adults to be recruited but within
specified age ranges (40). The target population could not be identified in the
remaining 141 trials (16%).
The intervention was a drug in 651 (72%) trials compared
with a process such as education, training or service delivery in 108 (12%)
trials, a procedure such as radiation therapy or surgery in 55 (6%) trials, and
a device in 49 (5%) trials. The interventions in the remaining 37 (4%) trials
included dietary interventions, alternative therapies or were unable to be
determined.
DiscussionThe number of trials undertaken in New Zealand in 2005-2009
has increased to an average of 180 trials per year, up from an average of 111
per year in 1998-2003.2 Growth that appeared to
have started in 2003 has been sustained. Much of the increase is due to early
phase activity, with 300% increase in activity from an average of 14 trials per
year in 1998-2003. The proportion of trials that could be identified as being
listed on a WHO-compliant register has also increased to 84%, up from 32% in
2003.2
Internationally, this study remains the only nationwide
stock take of all clinical trial activity, with the exception of a similar
exercise undertaken in by one of the authors in
2004.2 The national organisation of the health
and disability ethics committees, an overarching operating standard, with
standardised national application form and annual reporting facilitates such a
stock take. Other national surveys have been limited to non-commercial trials
only or examined clinical trial registers for specific country
codes.5 6
This study demonstrates once more that ongoing monitoring of
trial activity in New Zealand is possible, especially if information currently
reported by ethics committees is used. Such an activity could be undertaken be
the relevant ministries, such as the Ministry of Health or the Ministry of
Research, Science and Technology. With very little added effort, information
that clearly identifies ethics applications as pertaining to a clinical trial,
the phase of the trial, whether it is registered or not and where, could be
included in the ethics committees’ annual reports for aggregation by a
ministry.
New Zealand is thought to provide an environment conducive
to increasing clinical trial activity: it is a resourceful and innovative
society, has a reputation for conducting world class research, and can produce
results on time, with added cost benefits when the New Zealand dollar is weak
against other currencies.7 These factors are
reflected New Zealand’s contribution to clinical trial publications per
million population over the last 60 years (791/million), which puts New Zealand
at number three after Sweden and Denmark.8
Similarly, New Zealand’s biomedical research
publications per million population 1990–2000 (309.2) are on par with that
of the United Kingdom (310.4) although well short of Sweden (714.3) and the USA
(451.2).9 Although it is not possible to
compare all clinical trial activity, the average number of non-commercial trials
conducted in New Zealand during 2005–2009 that were non-commercially
sponsored was 67 per year, comparable to the 66.5 per year conducted in the
United Kingdom during 1980–2002.5 There
is no doubt that New Zealand is a small player in clinical trial activity, but
it does punch above its weight.
The increase in trials being registered from 32% in 2003 to
84% in 2005–2009 can only be ascribed to the announcement by the ICMJE
that trials seeking publication in member journals had to be prospectively
registered on a register compliant with the WHO Minimal Registration Data
Set.4 Previous attempts to encourage
registration, such as legislative requirements in trials for life-threatening or
serious conditions, had little effect.10 That
100% of trials conducted in New Zealand were not registered cannot be explained
by the increase in early phase activity. Industry appears to be more compliant
with trials registration than the non-commercial sector and the commercial
sector accounts for the greater proportion of early phase trials in New Zealand
(38% of commercial trials compared to 22% of non-commercial trials).
Although industry was hesitant to ascribe voluntarily to
trials registration, citing commercial
sensitivity,11 our findings suggest industry
has overcome such reservations. The report of the health select committee
inquiry into improving the environment for clinical trials recommended that
trials conducted in New Zealand be registered with the Australia New Zealand
Clinical Trials Register (ANZCTR).12 However, a
possible barrier has arisen as the Health Research Council (HRC) is no longer
assisting with funding the ANZCTR, even though the HRC recommends registering on
the ANZCTR. Alternative sources of public funding from New Zealand are needed if
this register is to be maintained.
Clinical trials are defined by the WHO as being “any
research study that prospectively assigns human participants or groups of humans
to one or more health-related interventions to evaluate the effects on health
outcomes.”3 As such the WHO expectation
is that any trial from phase I onwards should be registered, although that
consideration was relaxed by the ICMJE 2005
statement.4
Ethics committees have a role in continuing improvement in
trials registration. The current national application form does ask if it is
intended to register a clinical trial, but there is no hint of necessity. If
ethics committees were to require trial registration prior to releasing ethical
approval, non-commercial sector performance would improve. Such an improvement
would be unlikely to influence approval times for commercially-sponsored trials
given industry’s already excellent record in trials registration.
This study was subject to three limitations. First, the
number of clinical trials for which ethical approval was sought may have been
underestimated despite our best efforts. If a study did not include adequate
descriptors to identify it as a trial or could not be identified as such from
internet searching it was excluded from selection. Second, we did not determine
where the trial took place. While locality organisations are included for each
trial approval in the ethics committees’ reports, it was not always
possible to determine where the trial was undertaken from such locality reports
and thus the information was not collated for analysis. However, we have
reported information by ethics committee, which allows some approximation of
trial activity at a regional level. Third, the ethics committee annual reports
do not specify if trials progress from approval to completion. While this study
details applications for ethical approval for trials, it therefore does not
definitively detail the number of trials initiated in New Zealand, as some
trials may have failed to recruit participants.
ConclusionThere has been an increase in clinical trial activity since
2005 and much of this increase is due to increased early phase activity. There
has been a dramatic increase in the proportion of trials registered, with
commercially-sponsored trials being more compliant with registration. Ethics
committees could improve the compliance of the non-commercial sector with trials
registration by requiring evidence of trial registration prior to providing
ethical approval.
Competing interests: None
declared.
Author information: Vickie Currie, Summer
Scholar, Faculty of Medicine and Health Sciences, University of Auckland; Andrew
Jull, Associate Professor, School of Nursing and Senior Research Fellow,
Clinical Trials Research Unit, School of Population Health, University of
Auckland
Acknowledgement: Vickie Currie was funded
through a University of Auckland Summer Scholarship.
Correspondence: Andrew Jull, Associate
Professor, School of Nursing, University of Auckland, Private Bag 92019,
Auckland, New Zealand. Fax: +64 (0)9 3767158; email: a.jull@auckland.ac.nz
References:
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