Why not use the

safer drug ?
Kei Miyazaki
 Case

Ø 19yo male with acute lower back pain

Ø No red flag signs for further workup

Ø Dx: Musculoskeletal pain

Ø Ed: exercise
Ø Tx: ibuprofen PO
 What I used to do
Ø 1st Choice: NSAID patch

sometimes…
NSAID GEL

both are very cheap (in Japan)

Ø NSAID PO is 2nd choice

 Do you use it ? Available ?
Ø Attending Dr said
‘NSAID Patch is very expensive. Never seen
prescribed.’
‘Have seen topical NSAID.’

Ø Ketoprofen Gel 10% (OTC)

$36.99
Ø Ketoprofen Gel 20%(prescribed)

Ø Well accepted in European countries

 Clinical Question

Is Topical NSAID as effective as oral

NSAID with less side effects for
patient with acute lower back pain ?
 Clinical Question Revised

Uptodate, Pubmed searched with no good

answer…

Broadened the scope

Is Topical NSAID as effective as oral

NSAID with less side effects for patient
with acute/chronic pain ?
 Pubmed search
"Anti-Inflammatory Agents, Non-Steroidal"[Mesh]
AND
"Administration, Topical"[Mesh]
AND
"Pain/drug therapy"[Mesh]

Limits: Meta-Analysis, Practice Guideline, Randomized

Controlled Trial, English
Compared topical vs oral…no difference but
Compared topical vs oral…no difference but…
 Needed RCT comparing
Topical vs Oral NSAID
UpToDate
： Investigational Approaches to the pharmacologic
thrapy of osteoarthritis

Ø Equivalence study of a topical diclofenac solution

(pennsaid) compared with oral diclofenac in
symptomatic treatment of osteoarthritis of the
knee: a randomized controlled trial.
　 J Rheumatol. 2004 Oct;31(10):1893-5.
 Abstract: Methods
Ø METHODS: A total of 622 men and women with
radiological evidence of primary knee OA and mild to
severe symptoms were randomly assigned to treatment
with a topical diclofenac solution plus placebo oral
capsules, or placebo topical solution plus oral
diclofenac (50 mg) capsules. Patients applied 50 drops
of study solution and took 1 study capsule 3 times daily
for 12 weeks. Efficacy variables were pain and physical
function, measured by the Western Ontario and
McMaster Universities (WOMAC) VA 3.1 OA Index, and
patient global assessment (PGA). Equivalence in the
per-protocol group was based on previously defined
ranges of clinically significant difference. Safety was
assessed by evaluation of adverse events, vital signs,
and laboratory data.
 Abstract: Results
Ø RESULTS: The difference in mean (95% CI) change scores (final
minus baseline) between treatments was 13.3 mm (-8.6 to 35.2)
for pain (total scale 500 mm), 71.0 mm (-2.4 to 144.5) for physical
function (total scale 1700 mm), and 4.3 mm (-1.2 to 9.8) for PGA
(total scale 100 mm). The CI for each efficacy variable fell within
the predefined equivalence ranges (pain, +/- 75 mm; physical
function, +/- 255 mm; PGA, +/- 20 mm), indicating that no
clinically relevant difference was found between the 2 treatment
arms. Safety analyses of patients applying topical diclofenac
solution revealed some minor skin irritation at the application site--
mostly skin dryness in 83/311 (27%) patients--but a significantly
reduced incidence, relative to oral diclofenac, of total and severe
gastrointestinal (GI) adverse events, including dyspepsia,
abdominal pain, diarrhea, and nausea. The number of patients
developing abnormal liver function tests (including clinically
significant elevation), hemoglobin, and creatinine clearance was
significantly higher in the oral diclofenac group.
 Source of funding
Ø Dimethaid Health Care Ltd. (Canada).
Ø Develops and commercializes PENNSAID® and related
products
Ø http://www.painstudy.com/PainDrugs/pennsaid.htm

The CONSORT (Consolidated Standards of Reporting Trials)

guidelines were developed by a team including journal
editors, clinical epidemiologists, and statisticians. They set
out standards that should be adhered to by those reporting
clinical trials. Most of the recommendations are based on
published evidence from the literature on the quality of
clinical research.
Criteira for PP(per protocol data)
 Are the results valid?
Ø Did intervention and control groups start
with the same prognosis?

l Were patients randomized? Yes

l Was randomization concealed?

Yes. Investigators, support staff, patients,
sposor’s clinical research personnel

l Were Patients in the study groups similar with

respect to known prognostic factors? Yes
 Are the results valid?
Ø Was prognostic balance maintained as the
study progressed? Yes

l To what extent was the study blinded?

Complete
 Are the results valid?
Ø Were the groups prognostically balanced at the
study’s completition? Almost Yes

l Was follow-up complete? Almost complete in ITT

analysis

l Were Patients analyzed in the groups to which they

were randomized? Yes, and No
l Was the trial stopped early? No
 What are the results ?
Ø How large was the treatment effect?
l Both topical and Oral group showed significant
improvement.
l Oral group might better improve physical function.
l Topical group showed less GI side effects, Less Lab
abnormalities, more skin rash (1/10 people)

l How precise was the estimate of the treatment

effect? Very precise
 How can I apply the results
to patient care ?
Ø Were the study patients similar to my patient?
Not really, younger, acute lower back pain

Ø Were all patient-important outcomes

considered? Yes

Ø Are the likely treatmet benefits worth the

potential harm and cost? Yes. Less side effect.
Not very expensive.