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MJA Vol 179 20 October 2003 403
RESEARCH
The Medical Journal of Australia ISSN:
0025-729X 20 October 2003 179 8 403-
407
©The Medical Journal of Australia 2003
www.mja.com.au
Research
CELECOXIB, THE FIRST COX-2-selec-
tive non-steroidal anti-inflammatory
drug (C2SN) to be developed, came
onto the Australian market in 1999, and
was listed on the Pharmaceutical Bene-
fits Scheme (PBS) in August 2000.
Rofecoxib, the second C2SN to come
onto the market, was listed on the PBS
in February 2001. The initial restric-
tions placed on the prescribing of these
agents were, for celecoxib, “chronic
arthropathies (including osteoarthritis)
with an inflammatory component”, and
for rofecoxib, “treatment of chronic
osteoarthritis with an inflammatory
component”.
Cyclooxygenase-1 (COX-1) inhibition
in the gastrointestinal tract (GIT) was
postulated as the reason for the
increased risk of serious upper-GIT
ulcers, perforation or bleeding associ-
ated with traditional non-steroidal anti-
inflammatory drug (NSAID) use.1
C2SNs were thought to have a better
gastrointestinal safety profile than tradi-
tional NSAIDs, because they selectively
inhibit COX-2, an immediate early gene
product which is rapidly induced in
response to inflammatory stimuli.2 The
manufacturers of C2SNs sponsored
very large clinical trials in patients with
osteoarthritis and rheumatoid arthritis
to assess the risk of a serious GIT event
with these drugs compared with tradi-
tional NSAIDs. The new drugs proved
equally efficacious, and appeared to be
associated with a lower relative risk of
serious upper GIT events.3,4
Soon after celecoxib was placed on
the PBS, many Australian general prac-
titioners (GPs) began to prescribe it,
leading to a large number of adverse
drug reaction (ADR) reports and a blow
out in government expenditure.5-7 The
aim of our study was to assess trends in
prescribing of the new agents by GPs,
and the profiles of general practice
patients who were prescribed COX-2-
selective NSAIDs during the early
adoption phase.
METHODS
The General Practice Research Net-
work (GPRN)8 comprises a national
sample of Australian GPs who provide
deidentified electronic longitudinal
patient records. Overall prescription
rates per 1000 encounters for tradi-
tional NSAIDs, celecoxib and
rofecoxib, and meloxicam, were calcu-
lated using all of the data (from 437
GPs and 5 957 768 patient encounters)
from all GPRN participants for the 3
years from 1 September 1999 to 30
September 2002.
Lessons from early large-scale adoption of celecoxib and rofecoxib
by Australian general practitioners
Stephen J Kerr, Andrea Mant, Fiona E Horn, Kevin McGeechan and Geoffrey P Sayer
ABSTRACT
Objective: To assess trends in the first two years of prescribing of COX-2-selective
non-steroidal anti-inflammatory drugs (C2SNs) by Australian general practitioners.
Design: Retrospective analysis of deidentified electronic patient records from GPs
enrolled in the General Practice Research Network (GPRN).
Setting and participants: Overall prescription rates for C2SNs and NSAIDs
were assessed for all GPRN participants (437 GPs) between 1 September 1999
and 30 September 2002. Also, three cohorts of patients, with at least 12 months of
prescription data, who received their first prescription for celecoxib between August
and October 2000 (Cohort 1, 2366 patients), celecoxib between February and April
2001 (Cohort 2, 640 patients), and rofecoxib between February and April 2001 (Cohort
3, 608 patients) were selected for further analysis.
Main outcome measures: Age and sex of patients; reason for prescription;
previously prescribed pain medications and concomitant use of medications that
could predispose to an adverse renal or bleeding event.
Results: Prescriptions for C2SNs increased dramatically after they were listed on the
Pharmaceutical Benefits Scheme (PBS). C2SN prescriptions for patients aged less
than 65 years accounted for 52.6%, 59.5% and 50.7% of those in Cohorts 1, 2 and 3,
respectively; large numbers of patients in the study cohort had reasons recorded for
prescription that did not comply with PBS restrictions, and between 36.7% and 61.3%
of patients in the three cohorts had not received a prescription for any pain medication
in the year before being prescribed a C2SN. Between 4.7% and 7.9% were
coprescribed drugs that could cause renal complications.
Conclusions: Rapid, early adoption of C2SNs by Australian GPs has resulted in
prescribing and drug use patterns that were not in accord with quality use of medicine
MJA 2003; 179: 403–407
(QUM) principles.
For editorial comment, see page 397
National Prescribing Service, Sydney, NSW.
Stephen J Kerr, BPharm, PhD , Decision Support Coordinator.
South East Health, Darlinghurst, NSW.
Andrea Mant, MD, MA, Area Advisor, Quality Use of Me dicines.
Health Communication Network, St Leonards, NSW.
Fiona E Horn, BSc, MPH, Research Analyst; Kevin McGeechan, BSc, Senior Research Analyst;
Geoffrey P Sayer, BSc(Psychol), MCH, General Manager - Research.
Reprints will not be available from the authors. Correspondence: Dr Stephen J Kerr, National
Prescribing Service, PO Box 1147, Strawberry Hills, NSW 2012. skerr@nps.org.au
RESEARCH
404 MJA Vol 179 20 October 2003
RESEARCH
Initially, two cohorts were identified
for further analysis, comprising patients
who had received their first prescription
for either celecoxib or rofecoxib in the
three months after their listing on the
PBS. We also selected an additional
cohort of patients who had received
their first prescription for celecoxib after
it had been listed on the PBS for six
months to see if the pattern of use had
changed.
To maximise the chances of obtaining
comprehensive data for each patient, we
included only the patients of GPs from
practices where all members of the
practice were also members of the
research network. Thirty-eight practices
where all GPs were enrolled with the
GPRN were identified. The patients of
ninety-six GPs from these practices
were included in the cohorts for the
C2SN analysis. The resulting database
of 796 537 prescription records from
January 1999 for the 96 GPs was
searched for patients receiving their first
prescription for celecoxib or rofecoxib.
To permit retrospective analysis,
inclusion in the cohorts was restricted
to patients whose records had prescrip-
tion data available for the 12 months
preceding their first C2SN prescription.
The first celecoxib cohort (Cohort 1)
comprised 2366 patients who received
their first prescription for celecoxib
between 1 August and 31 October
2000. The second celecoxib cohort
(Cohort 2) comprised 640 patients who
received their first celecoxib prescrip-
tion between 1 February and 30 April
2001. The rofecoxib cohort (Cohort 3)
comprised 608 patients who received
their first prescription for rofecoxib also
between 1 Februar y and 30 April 2001.
Data extracted from the electronic
health records of patients in these three
cohorts included patient age and sex,
reason for C2SN prescription, pain
medications prescribed in the previous
12 months, coprescription of aspirin,
and coprescription of other medications
which are known to adversely affect
renal function when prescribed together
with C2SNs (ie, diuretics, angiotensin-
converting enzyme inhibitors [ACEI],
angiotensin-2 receptor antagonists
[AT2A]).9
Statistical analysis
We used SAS software for analyses.10
Standard errors and confidence inter-
vals were calculated incorporating a
cluster sample study design using
“PROC SURVEYMEANS” (a pro-
gramming command within the SAS
programming language).
RESULTS
Overall use of new and old drugs
Prescriptions written for celecoxib
increased dramatically from August
2000, when the drug was first made
available on the PBS (Box 1). In the
first month, celecoxib was the most
frequently prescribed item among all
GPRN doctors, accounting for 44.8
prescriptions written per 1000 patient
encounters, and overtaking total pre-
scriptions for all NSAIDs. This rate
gradually fell over the next 7 months,
stabilising at about 15 prescriptions per
1000 patient encounters. Prescriptions
for rofecoxib increased, but not as dra-
matically, and the rate plateaued at
about 13 prescriptions per 1000 patient
encounters. Rate of prescribing of tradi-
tional NSAIDs did not fall after
rofecoxib was listed on the PBS in
February 2001, although the prescrip-
tion rates for celecoxib decreased. The
sum of the prescribing rates for C2SNs
and traditional NSAIDs increased to a
level about 20% higher than rates for
traditional NSAIDs alone had been
before C2SNs became available on the
PBS.
Age and sex of patients
The mean age of patients in the three
cohorts was 61 years (median, 63 years;
range, 12–96 years). In Cohorts 1–3,
patients aged less than 50 years
accounted for 22.8%, 28.2% and
20.8%, respectively, of those for whom
C2SNs were prescribed, and those aged
less than 65 years accounted for 52.6%,
59.5% and 50.7%, respectively.
Reason for prescription
Once enrolled in the GPRN, GPs are
required to enter their reason the first
time they prescribe a particular drug for
a patient. However, as we used some
retrospective prescribing data (from
before GPs were enrolled), reasons were
not always recorded. Thus, 38.9% of
patients in Cohort 1 for whom C2SNs
were prescribed had reasons for pre-
scription recorded, increasing to 87.7%
and 93.1% in Cohorts 2 and 3, respec-
tively.
In all three cohorts, “osteoarthritis”
or “arthritis” were the most frequently
recorded reasons, and, together,
accounted for between 37% and 47% of
patients being prescribed C2SNs in
each cohort (Box 2). Rheumatoid
arthritis was recorded as the reason for
prescribing C2SNs for less than 3% of
1: Prescription rate per 1000 patient encounters of C2SNs and NSAIDs,
showing the time of Pharmaceutical Benefits Scheme (PBS) listing for
celecoxib, rofecoxib and meloxicam
0
10
20
30
40
50
60
70
80
NSAIDs + C2SNs
Total C2SNs
Rofecoxib
Rofecoxib
NSAIDs
Meloxicam
Meloxicam
Celecoxib
Time of PBS listing
Celecoxib
Sep-02
Jul-02
May-02
Mar-02
Jan-02
Nov-01
Sep-01
Jul-01
May-01
Mar-01
Jan-01
Nov-00
Sep-00
Jul-00
May-00
Mar-00
Jan-00
Nov-99
Sep-99
Rate per 1000 patient encounters
MJA Vol 179 20 October 2003 405
RESEARCH
patients in any cohort, reflecting the low
prevalence of this condition in the pop-
ulation. Remaining reasons were prima-
rily musculoskeletal conditions.
Past-year pain medication
Between 36.7% and 61.3% of patients
in the three cohorts had not received a
prescription for any pain medication in
the year before being prescribed a
C2SN (Box 3). Varying proportions of
patients in the three cohorts received
prescriptions for traditional NSAIDs,
paracetamol, combinations of paraceta-
mol and codeine, or other pain medica-
tions, in the 12 months preceding their
first C2SN prescription. Fewer than
33.2% of patients in any cohort had
been prescribed a traditional NSAID,
and fewer than 47.7% had been pre-
scribed paracetamol or a paracetamol
and codeine combination; 31.6% of
patients in the rofecoxib cohort had
previously been prescribed celecoxib.
Concomitant use of relevant medications
Box 4 gives the frequency for each
cohort of concomitantly prescribed
medications that could predispose
patients to a serious adverse renal or
bleeding event.9 Between 4.7% and
7.9% of patients were prescr ibed a
C2SN, diuretic and either an ACEI or
AT2A .
DISCUSSION
Two years after the introduction and
rapid adoption of celecoxib and
rofecoxib, there has been an overall
growth in the market for anti-inflamma-
tory medications. In our general prac-
tice study, prescribing rates per 1000
consultations for C2SNs plus tradi-
tional NSAIDs increased by about 20%.
There are several caveats in interpret-
ing data from the GPRN database.
Firstly, it comprises only a sample of
GPs (although GPRN participants are
representative of Australian GPs
overall8). Secondly, it is possible that
datasets may be incomplete, as patients
may visit more than one GP. A final
caution relates to uncertainty of reasons
for prescription recorded in the absence
of recognised standard disease coding
criteria. Notwithstanding these limita-
tions, the GPRN allows overall pre-
scribing rates of C2SNs and NSAIDs to
be calculated; this cannot be done by
using the Health Insurance Commis-
sion database, as it does not capture
prescriptions for traditional NSAIDs
that fall below the patient copayment.
The increase in COX-2 prescribing
coincided with a period of energetic
marketing to the medical profession,
which promoted the message that the
new C2SNs were “safer” than tradi-
tional NSAIDs.11 While the studies
available at that time suggested that
treatment with C2SNs was associated
with a lower risk of a serious upper GI
event, the adverse event profile was
otherwise not appreciably different to
that for traditional NSAIDs.3,4 In Aus-
tralia and the United States, there was
also an extensive campaign to promote
celecoxib to consumers through televi-
sion and newspaper coverage.12,1 3
Less than a third of the patients in any
of our cohorts who were introduced to a
C2SN had been prescribed a traditional
NSAID in the previous year, and
between 36.7% and 63.3% had not
been prescribed any pain medication in
the previous year. A large proportion of
patients were aged under 65 years.
Major recorded reasons for prescribing
were osteoarthritis or arthritis, with few
being for rheumatoid arthritis. Many
patients appeared to have received
C2SNs as first-line therapy. Interna-
tional and Australian guidelines pub-
lished after the time of our study advise
that C2SNs are most useful for patients
who need maximum doses for a pro-
longed time, or for those aged over 65
years.9,14,15
A proportion of patients may have
previously experienced gastrointestinal
toxicity with traditional NSAIDs, but
this could not be determined from our
2: Top 10 reasons for prescribing celecoxib and rofecoxib in study cohorts
Cohort 1* (2366 patients) Cohort 2† (640 patients) Cohort 3‡ (608 patients)
Reason for prescribing n% (95% CI)§n% (95% CI) n% (95% CI)
Osteoarthritis 253 27.5 (21.4–33.6) 107 19.1 (13.2–24.9) 158 27.9 (19.0–36.8)
Arthritis 183 19.9 (14.6–25.1) 101 18.0 (12.8–23.2) 103 18.2 (8.6–27.8)
Pain other than knee/back 105 11.4 (7.7–15.1) 82 14.6 (10.2–19.0) 78 13.8 (8.1–19.5)
Backpain 74 8.0 (5.2–10.9) 61 10.9 (7.1–14.6) 37 6.5 (3.9–9.2)
Knee pain 17 1.8 (0.6–3.1) 24 4.3 (2.4–6.2) 14 2.5 (0.7–4.2)
Injury/sprain/strain 18 2.0 (1.1–2.9) 19 3.4 (0.5–6.3) 10 1.8 (0.6–2.9)
Sciatica 16 1.7 (0.5–2.9) 14 2.5 (1.2–3.8) 9 1.6 (0.4–2.8)
Arthralgia 10 1. 1 (0.3–1.9) 10 1.8 (0.5–3.1) 6 1.1 (0.0–2.3)
Gout 10 1.1 (0.5–1.7) 9 1.6 (0.0–3.2) 3 0.5 (0.0–1.1)
Spondylosis 30 3.3 (1.7–4.9) 8 1.4 (0.0–2.8) 21 3.7 (1.1–6.3)
Rheumatoid arthritis 10 1.1 (0.3–1.9) 6 1.1 (0.0–2.1) 15 2.7 (1.4–3.9)
Tendonitis 4 0.4 (0–0.9) 6 1.1 (0.1–2.0) 9 1.6 (0.2–3.0)
Reason for script recorded 921 38.9 561 87.7 566 93.1
* Celecoxib first prescribed Aug–Oct 2000. † Celecoxib first prescribed Feb–Apr 2001. ‡ Rofecoxib first prescribed Feb–Apr 2001. § Percentages are calculated as a
proportion of prescriptions where a reason for prescribing was recorded by the general practitioner.
406 MJA Vol 179 20 October 2003
RESEARCH
study. Nevertheless, the extent of C2SN
prescribing in the absence of previous
prescribed pain medication suggests
that GPs were ready to adopt a newer
“safer” agent for their patients whatever
their actual level of GIT risk. Impor-
tantly, continued controversy over the
methods and analyses of the CLASS3
and VIGOR4 trials, together with the
current level of uncertainty over the
absolute ratio of risk to benefit of C2SN
therapy, indicate that assumptions of
superior safety were premature.16-1 8
Another possible explanation for the
scale of early use of these drugs may have
been the way the restriction was worded
in the PBS. It is debatable how strongly
the existence of a restriction weighs with
prescribers, as, unlike an authority word-
ing, no special effort is required to obtain
the drug for the patient. In any event, the
initial restriction in the PBS listing for
celecoxib (“chronic arthropathies
[including osteoarthritis] with an inflam-
matory component”) did not differ from
that for traditional NSAIDs. Whatever
was intended, it seems no special mes-
sage was received by prescribers through
these listings (see Box 1). The fall in
prescribing for celecoxib and the plateau
in prescribing for both agents presuma-
bly reflected the inevitable reassessment
of its effectiveness and safety after the
initial marketing and promotion.
It is particularly interesting that a
third of the patients in Cohort 3 had
previously been prescribed celecoxib,
suggesting that these patients did not
tolerate or were not happy with the
efficacy of this medication.
Our study also indicates the potential
for adverse effects with widespread use
of C2SNs. Terminology and acronyms
used for the new agents have had many
variants in the short time since they
were released, reflecting the debate over
the extent to which they are indeed a
new drug class.19 However, their pro-
motion as a new class may have left
general practitioners without the
reminder that the new agents, like the
old, can cause renal impairment and
fluid retention.20 The risk of these
adverse effects is increased by concomi-
tant therapy with diuretics, ACE inhibi-
tors or AT2As, and is further
exacerbated when ACE inhibitors or
AT2As are taken together with diuretics
and C2SNs or NSAIDs.7, 20 Despite
this, between 4.7% and 7.9% of
patients in our three cohorts were being
treated with this combination of three
agents. These findings are consistent
with those of a clinical audit under taken
with Australian rural GPs.21
More generally, the potential for
adverse effects is greater when prescrib-
ing a new drug soon after its release
onto the market. It has been shown that
early adopters put their patients at risk
of adverse effects.22 A recent study
found that 10% of new drugs approved
by the US Food and Drug Administra-
tion between 1975 and 1999 were either
withdrawn from the market or acquired
a “black box” warning (a US labelling
device aimed at increasing drug safety)
as a result of newly discovered adverse
drug reactions.23 Indeed many adverse
events, particularly those that are idio-
syncratic and not expected from a
4: Medications concomitantly prescribed with COX-2-selective non-steroidal anti-inflammatory drugs that
potentially increase the risk of adverse renal events or bleeding
Cohort 1* (2366 patients) Cohort 2† (640 patients) Cohort 3‡ (608 patients)
Coprescribed medication n% (95% CI) n% (95% CI) n% (95% CI)
Diuretic 279 11.8 (10.2–13.4) 52 8.1 (5.3–11.0) 66 10.9 (8.2–13.5)
ACEIs 273 11.5 (9.1–14.0 ) 53 8.3 (6.4–10.1) 60 9.9 (7.5–12.2)
AT2As 132 5.6 (3.0–8.1) 22 3.4 (1.6–5.3) 45 7.4 (5.4–9.4)
Combination ACEI/diuretic 97 4.1 (3.0–5.2) 16 2.5 (1.5–3.5) 27 4.4 (2.9–6.0)
Combination AT2A/diuretic 54 2.3 (1.0–3.6) 14 2.2 (1.1–3.3) 21 3.5 (2.3–4.6)
Warfarin 16 0.7 (0.3–1.1) 6 0.9 (0.2–1.7) 2 0.3 (0.0–0.7)
Aspirin 183 7.7 (5.2–10.3) 20 3.1 (1.7–4.5) 47 7.7 (5.1–10.4)
ACEI =angiotensin-converting enzyme inhibitor; AT2A =angiotensin-2 receptor antagoni st.
* Celecoxib fir st prescribed Aug–Oct 2000. † Celecoxib first prescribed Feb–Apr 2001. ‡ Rofecoxib first prescribed Feb–Apr 2001.
3: Prescription for pain medications in the 12 months preceding first prescription for celecoxib or rofecoxib
Cohort 1* (2366 patients) Cohort 2† (640 patients) Cohort 3‡ (608 patients)
Prescribed pain medication§n% (95% CI) n% (95% CI) n% (95% CI)
Traditional NSAID¶785 33.2 (29.4–36.9) 124 19.4 (15.0–23.7) 169 27.8 (22.4–33.2)
Celecoxib¶— — — — 192 31.6 (27.1–36.0)
Paracetamol¶493 20.8 (17.5–24.2) 98 15.3 (12.7–17.9) 164 27.0 (20.0–34.0)
Paracetamol/codeine¶419 17.7 (15.7–19.8) 81 12.7 (8.8–16.5) 126 20.7 (15.2–26.2)
Other pain medication¶,** 182 7.7 (5.9–9.4) 39 6.1 (4.4–7.8) 89 14.6 (10.7–18.5)
No prescribed pain medication 1095 46.3 (41.8–50.8) 392 61.3 (55.4–67.1) 223 36.7 (31.8–41.6)
* Celecoxib first prescribed Aug–Oct 2000 . † Celecoxib first prescribed Feb–Apr 2001. ‡ Rofecoxib first prescribed Feb–Apr 2001. § Refers to the 12 months preceding
the first prescription for celecoxib or rofecoxib. ¶ These groups are not mutual ly exclusive. ** Includes codeine alone, trama dol, combination dextropropoxyphene/
paracetamol, and morphine.
MJA Vol 179 20 October 2003 407
RESEARCH
drug’s pharmacological properties, may
not manifest until a medication has
been in routine clinical use for a
number of years.
A number of lessons can be gleaned
from the Australian experience of large-
scale early adoption of celecoxib and
rofecoxib by GPs. Intense drug promo-
tion can create perceptions about medi-
cines that strongly influence patterns of
prescribing and use, yet may not be in
line with best available evidence. Fur-
ther, such rapid uptake can place
patients at risk of adverse drug reactions
and serious drug interactions through
coprescribing. The Quality Use of Med-
icines (QUM) arm of the Australian
National Medicines Policy dictates that
prescribing should be judicious, safe,
appropriate, and cost-effective.24 Our
view is that transparency and collabora-
tion between regulatory agencies, the
pharmaceutical industry and organisa-
tions such as the National Prescribing
Service are needed if new medications
are to be prescribed and used in a way
that enhances the health of individuals
and also adheres to QUM principles.
COMPETING INTERESTS
In 1997, Associate Professor Andrea Mant provided con-
sultancy advice on Quality Use of Medic ines to Merck
Sharp & Dohme.
REFERENCES
1. Henry D, Lim LL, Garcia Rodriguez LA, et al. Varia-
bility in risk of g astrointestin al comp lications with
individual non-steroidal anti-inflammatory drugs:
results of a collaborative meta-analysis. BMJ 1996;
312: 1563-1566.
2. Hawkey C J. COX-2 in hibitors. Lancet 1999; 353:
307-314.
3. Silverstein FE, Faich G, Goldste in JL, et al. Gast roin-
testinal toxicity with celecoxib vs nonsteroidal anti-
inflammatory drugs for osteoarthritis and rheumatoid
arthritis: the CLASS study. A randomized controlled
trial. Celecoxib Long-term Arthritis Safety Study.
JAMA 2000; 284: 1247-1255.
4. Bombardier C, Laine L, Reicin A, et al. Comparison
of upper gastrointestinal toxicity of rofecoxib and
naproxen in patients with rheumatoid arthritis.
VIGOR Study Group. N Engl J Med 2000; 343: 15 20-
1528.
5. Davies JA. Arthritis drug under siege. The Age
(Melbou rne) 6 Fe b 2001; Sect : News: 1.
6. Your reports at work — drug safety in Australia. Aust
Advers e Drug Reac t Bull 2001 ; 20(4): 15-1 6.
7. Boyd IW, Mathew TH, Thomas MC. COX-2 inhibitors
and renal failure: the triple whammy revisited. Med J
Aust 2000; 173: 274.
8. Sayer GP, McGeechan K, Kemp A, et al. The Gen-
eral Pra ctice Res earch Network: the c apabilitie s of
an electronic patient management system for longi-
tudinal patient data. Pharmacoepidemiol Drug
Safety 2003; 12: 48 3-489
9. Therape utic guidelines: a nalgesic. 4th ed. Mel-
bourn e: Therape utic Guidel ines Limit ed; 2002.
10. SAS. Version 8 [computer program]. Cary, NC: SAS
Institute Inc, 2002.
11. Mansfield P. Healthy scepticism about Pfizer and
Searle’s promot ion of celecoxib in Austra lia. Healthy
Skepticism Int Ed March/A pril 2000; 18 (3/4). Availa-
ble at: www.healthyskepticism.org/editions/
IN0004.htm (accessed Dec 2002).
12. Davies J- A, Foley B. A dr ug that w as sold on hope.
The Age (Melbourne) 10 Feb 2001; Sect: News: 1.
13. Anderson WB. The media battle between Celebrex
and Vioxx: influencing media coverage but not con-
tent. Public Rela t Rev 2001; 27: 449-460.
14. Maetzel A, Krahn MD, Naglie G. Economic assess-
ment: celecoxib and rofecoxib for patients with
osteoarthritis and rheumatoid arthritis. Ottawa:
Canadian Coordinating Office for Health Technology
Assessment; 2002. Report No.: Technology Over-
view Number 6. Available at: www.ccohta.ca/
(accessed May 2003).
15. Guidance on the use of cyclo-oxygenase (COX) II
selective inhibitors, celecoxib, rofecoxib, meloxicam
and etodolac for osteoarthritis and rheumatoid
arthritis . London: N ational Institute for Clin ical Excel-
lence; July 2001. Report No.: NICE Technology
Appraisal Guidance Numbe r 27. Available at:
www.nice.org.uk/pdf/coxiifullguidance.pdf
(accessed May 2003).
16. Jones R. Efficacy and safety of COX 2 inhibitors.
BMJ 2002; 32 5: 607-60 8.
17. Juni P, Rutjes AW, Dieppe PA. Are selective COX 2
inhibitor s superior to t raditional no n steroidal anti-
inflammatory drugs? BMJ 2002; 324: 1287-1288.
18. Lassere M, Johnson K. The power of the protocol.
Lancet 2002; 360: 1620-1622.
19. Lipsky LP, Abramson SB, Crofford L, et al. The
classification of cyclooxygenase inhibitors. J Rheu-
matol 1998; 25: 2298-2303.
20. The Australian COX-2-Specific Inhibitor (CSI) Pre-
scribing Group. Considerations for the safe pre-
scribing and use of COX-2-specific inhibitors
[position statement]. Med J Aust 2002; 176: 328-
331.
21. Cutts C, LaCaze A, Tett S. A clinical audit of the
prescrib ing of cele coxib and rofecoxib in A ustralian
rural general practice. Br J Clin Pharmacol 2002; 54:
522-527.
22. Inman W, Pearce G. Prescriber profile and post-
market ing surveillance. Lanc et 1993; 342: 658-661.
23. Lasser KE, Allen PD, Woolhandler SJ, et al. Timing of
new black box warnings and withdrawals for pre-
scription medications. JAMA 2002; 287: 2215-2220.
24. National medicines policy 2000. Canberra: Com-
monwea tlh Depa rtment of Health an d Aged Care;
1999.
(Received 15 Jan 2003, accepted 18 Jun 2003) ❏
