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TAASS
FAQs
Content
FAQ
Slide no.
Why was diclofenac used as a comparator treatment?
4
Is it of benefit to use Traumeel as soon as possible if ankle sprains are benign
and self-limiting?
5
Why was ankle sprain chosen as the musculoskeletal disorder to investigate in
the TAASS study?
6 - 10
Is 1% diclofenac gel the same as Voltaren Emulgel?
11
Why did the TAASS study investigate Traumeel ointment and gel – why not
Traumeel tablets or ampoules?
12 - 13
Is there a beneficial effect on tissue repair and healing with Traumeel?
14 - 16
What is an adverse event?
17
What is an adverse drug reaction?
18
What about adverse events in the TAASS study?
19
Summary of Adverse Events in the TAASS Study
20
Content
FAQ
Why was the Orizola study never published?
Why are there different study outcomes between the TAASS and the Orizola
studies?
Slide no.
21
22-23
What about blinding in the TAASS study?
24
Are other formulations of Traumeel available?
25
What is the VAS Score?
What is the FAAM ADL Score?
What is the “figure-of-eight” method as used for swelling measurement?
Are there any known drug interactions and contraindications?
Summary
26-27
28
29 - 30
31
32 - 33
Why was diclofenac used as a comparator
treatment?
NSAIDS are commonly used to treat musculoskeletal disorders
Diclofenac is the most widely used NSAID1
Reviews of diclofenac have consistently demonstrated its efficacy in
reducing pain and inflammation in acute and chronic conditions
compared with placebo2-4
● Of particular relevance is that these studies included treatment of
adult patients with acute pain resulting from strains, sprains or
sports or overuse-type injuries (twisted ankle, for instance)
These findings support the use of a treatment that is considered
“standard” and remove the need for a placebo-control arm
1. MeReC rapid review. 2011. http://www.npc.nhs.uk/rapidreview/?p=2451
2. Banning M. Expert Opin Pharmacother. 2008 Nov;9(16):2921-9;
3. Zacher. Curr Med Res Opin. 2008 Apr;24(4):925-50; 4. Pain. 2009
Jun;143(3):238-45
Is it of benefit to use Traumeel as soon as possible if
ankle sprains are benign and self-limiting?
Ankle sprains are common injuries generally believed to be benign
and self limiting
Despite the estimated level of follow-up medical care, ankle sprains
are considered undertreated by the medical community1
Studies report a significant proportion of patients with ankle sprains
having persistent symptoms for months or even years2
Without adequate care, acute ankle trauma can result in chronic joint
instability3
Prevention and early effective treatment are considered essential2-3
1. Stanley KL. Ankle sprains are always more than “just a sprain.” Postgrad
Med.1991;89:251-255; 2. Anandacoomarasamy A , Barnsley L. Br J Sports
Med 2005;39; 3. Wolfe MW. Am Fam Physician 2001;63:93-104.
Why was ankle sprain chosen as the musculoskeletal
disorder to investigate in the TAASS study?
Ankle sprain is one of the four most common soft tissue injuries (ref
IMS)
Because the ankle is a load-bearing joint, success in this area is
indicative of treatment success for Traumeel in other parts of the
body
Why was ankle sprain chosen as the musculoskeletal
disorder to investigate in the TAASS study?
A recent review of topical NSAIDs suggested that most studies
enrol participants with sprains, strains and contusions as a
result of sports injuries1
Many studies group all injuries together rather than examine
treatment effects on specific injuries are warranted
There are potential differences in response to treatment
between strains and sprains and overuse-type injuries1
Large studies of good methodological quality and well-defined
diagnostic criteria and outcome measures are needed to
confirm the comparative beneficial and adverse effects of
topical diclofenac in painful and inflammatory conditions.1,2
1. Massey T et al. Cochrane Syst Rev 2010(6):CD007402; 2. Zacher J et al. Curr Med Res
Opin 2008;24:925–950
TAASS versus other study methodology (i)
Study
Drug
Comparator
Population
Mean age
% male
Trial
duration
Outcomes
TAASS
Acute ankle
sprain
RCT
Double blind
Single blind
Traumeel®
ointment 2 g
3 x daily; or
Traumeel® gel
2g
3 x daily
diclofenac gel
1%
2g
3 x daily
N = 449
~28 years
73%
42 days
VAS ankle (maximum) pain;
functional impairment [Foot and Ankle
Ability Measurement (FAAM), Activity
of Daily Living Subscale; FAAM Sports
Subscale; normal function]; swelling;
global efficacy; rescue medication
Adverse effects; local tolerability
Schermer
1991
Fresh sprains
of upper
ankle joint
RCT
Double blind
diclofenac
diethylamine
gel 1.16%
4g
3 x daily
Placebo gel
N = 80
~22 years
100%
14 days
VAS pain scores (lying, standing,
pressure, movement); functional
impairment; hyperthermia; joint
circumference; size of lower leg;
rescue medication; treatment
acceptance of treatment
Adverse effects
Campbell et
al 1994
Acute ankle
sprain (<24
h)
RCT
Double blind
Ibuprofen
cream 5%
4”
4 x daily
Placebo cream
N = 37
~29 years
65%
7-14 days
VAS pain on walking; improvement in
walking ability;withdrawals;
exclusions; rescue medication
VAS, visual analogue scale
Schermer R. Wehrmed Mschr 1991;9:415-9; Diebshlag W et al. J Clin Pharmacol
1990;30:82-89; Campbell J et al. J Accid Emerg med 1994;11:78-82.
TAASS versus other study methodology (ii)
Study
Drug
Comparator
Population
Mean age
% male
Trial
duration
Outcomes
TAASS
Acute ankle
sprain
RCT
Double blind
Single blind
Traumeel®
ointment 2 g
3 x daily; or
Traumeel® gel
2g
3 x daily
diclofenac gel
1%
2g
3 x daily
N = 449
~28 years
73%
28 days
VAS ankle (maximum) pain;
functional impairment [Foot and Ankle
Ability Measurement (FAAM), Activity
of Daily Living Subscale; FAAM Sports
Subscale; normal function]; swelling;
global efficacy; rescue medication
Adverse effects; local tolerability
Diebshlag
et al 1990
Ankle sprain
RCT
Double blind
Ketorolac gel
2%
3g
3 x daily
Etofenamate
gel 5%
3g
3 x daily
Placebo gel
N = 37
28 years
65%
15 days
Improvement in VAS pain
Adverse events; withdrawals;
exclusions
Dreiser et
al 1990
Uncomlicated
ankle sprain
(<4 days)
RCT
Double blind
Niflumic acid
gel 2.5%
5g
3 x daily
Placebo gel
N = 60
33 years
50%
7 days
Improvement in VAS pain; patient
global evaluation
Adverse events; withdrawals;
exclusions
VAS, visual analogue scale
Diebshlag W et al. J Clin Pharmacol 1990;30:82-89; Dreiser RL et al. Curr Med Res Opin
1990;12:93-99
TAASS versus other study methodology (iii)
Study
Drug
Comparator
Population
Mean age
% male
Trial
duration
Outcomes
TAASS
Acute ankle
sprain
RCT
Double blind
Single blind
Traumeel®
ointment 2 g
3 x daily; or
Traumeel® gel
2g
3 x daily
diclofenac gel
1%
2g
3 x daily
N = 449
~28 years
73%
28 days
VAS ankle (maximum) pain;
functional impairment [Foot and Ankle
Ability Measurement (FAAM), Activity
of Daily Living Subscale; FAAM Sports
Subscale; normal function]; swelling;
global efficacy; rescue medication
Adverse effects; local tolerability
Dreiser et
al 1994
Traumatic
ankle sprain
RCT
Double blind
Flurbiproten
patch
40 mg
2 x daily
Placebo patch
N = 131
34 years
64%
7 days
Improvement in VAS pain; patient
global evaluation
Adverse events; withdrawals;
exclusions
Mazieres et
al 2005
Acute ankle
sprain
RCT
Double blind
Ketoprofen
patch
100 mg
1 x daily
Placebo patch
N = 172
46 years
42%
14 days
Patient global evaluation
Adverse events; withdrawals
VAS, visual analogue scale
Dreiser RL et al. Eur J Rheum Inflam 1994;14:9-13; Mazieres B et al. Am J Sport Med
2005;33:515-523
Is 1% diclofenac gel the same as Voltaren
Emulgel?
Both contain the same amount of active substance, while excipients
vary slightly
Diclofenac 1% gel used in the TAASS study:
● diclofenac gel 1%; Standard Brand with 10 mg/g Diclofenac
● excipients: propylenglycol, propan-2-ol, hypromellose,
macrogolglycerolcocoate (Ph.Eur.), purified water
Voltarol 1.16% Emulgel, gel:
● 1 g of Voltarol Emulgel contains 11.6 mg of the active substance,
which corresponds to 10 mg diclofenac sodium
● excipients: diethylamine, carbomer, macrogol cetostearyl ether,
cocyl caprylocaprate, isopropyl alcohol, liquid paraffin heavy,
perfume creme 45, propylene glycol dist., and water
Why gel and ointment and not tablets and
ampoules?
This study aimed to compare topical preparations only
Further studies have demonstrated the efficacy of oral and
systemic administration of Traumeel
Traumeel has previously been reported to be well tolerated and
without treatment-related adverse effects,1-9 including in:
● patients with other indications, e.g. various musculoskeletal
sports injuries, post-traumatic hemarthrosis, epicondylitis
● other studies using ointment, and other routes of
administration, e.g. injection, and tablets
This topical study is a robust addition to the Traumeel
evidence base and ensures that the product can be seen
as an effective treatment option for musculoskeletal
disorders
1. Arora S, Harris T, Scherer C. Biol Ther2000;XVIII(2):222–5 ; 2. Schneider C et al. Explore.
2005;1:446–452; 3. Böhmer D & Ambrus P. Biol Ther. 1992;10:290–300; 4. Thiel W. Biol Ther.
1994;XII:242–248; 5. Birnesser H et al. J Musculoskel Res. 2004;2/3:119–128; 6. Zenner S &
Metelmann H. Biol Ther. 1992;X:301–310; 7. Zenner S & Metelmann H. 1994;XII:204–211;
8. Zenner S & Weiser M. Biomed Ther.1997;XV:22–26; 9. Schneider C et al Complement Ther
Med. 2008;16:22–27
Why gel and ointment and not tablets or
ampoules?
Both are commonly used preparations for musculoskeletal injuries
● Use of Traumeel ointment and gel without prior presentation to a
healthcare professional
● Availability of ointment and gel as an over-the-counter and
prescription medicine
Availability of a NSAID in a comparable presentation form
● Diclofenac gel has a comparatively low side effect profile
compared to oral NSAIDs and is therefore a more fair comparison
to Traumeel that is known to be well tolerated
● Use of diclofenac gel without prior presentation to a healthcare
professional
● Availability of gel as an over-the-counter and prescription
medicine
Is there a beneficial effect on tissue repair and
healing with Traumeel (i)?
This topical study is a robust addition to the Traumeel
evidence base and ensures that the product can be seen as an
effective treatment option for musculoskeletal disorders
Evidence from in vitro and pre clinical studies show that the
mechanism of action of Traumeel has a beneficial effect on both
tissue repair and accelerated wound healing1-5
● It can be concluded that components of Traumeel may promote recovery
and may speed up the healing process
● Traumeel provides a multitargeted, synergistic action to address multiple
aspects of the inflammatory process and may promote healing
Another reason to switch to Traumeel – better tolerability with
the added benefit of multitargeted mechanism of action
1.Heine H, Schmolz M. Biomed Ther. 1998;XVI(3):224–226. 2. Heine H, Andrä F. Ärztezeit
f Naturheilverfahrenn. 2002;43(2):96–104. 3. Lussignoli S et al. Complement Ther Med.
1999;7(4):225–230. 4. Porozov et al. Clin Dev Immunol. 2004;11(2):143–149. 5. Conforti
A et al. Biomed Ther. 1997;XV(1):28–31.
NSAIDs adversely affect tissue healing (ii)
Challenging the premise that NSAIDs and selective COX inhibitors will
not affect tissue healing, in vitro and animal studies suggest that
they:
● impede tissue repair by retarding inflammation, i.e. reduce wound
strength in terms of tensile strength1
● inhibit angiogenesis through direct effects on endothelial cells2
● are a risk factor for bone healing impairment3
● reduce osteoblast numbers in a dose-dependant manner and increased
collagen synthesis and alkaline phosphatase activity4
● inhibits tendon cell migration to the repair site where there is tendon
damage5
● have a detrimental effect during early tendon repair, but might be of value
during remodelling due to the negative influence of inflammation.6
1. Dvivedi S. Indian J Exp Biol 1997;35: 1243-5; 2. Jones MKH, et al. Nat Med 1999;5: 1418-23; 3. Pountos
I, et al. Sci World J 2012:606404. Epub 2012 Jan 4; 4. Evans CE & Butcher C. J Bone Joint Surg Br
2004:86: 444-9; 5. Tsai W, et al. J Orthop Res 2006;24:551-8; 6. Virchenko O, et al. Am J Sports Med
2004;32: 1743-7.
NSAIDs adversely affect tissue healing (iii)
Challenging the premise that NSAIDs and selective COX inhibitors will
not affect tissue healing, in vitro and animal studies suggest that:
● they may have potentially negative effects during the proliferative phase of
a healing since it was associated with decreased DNA synthesis1
● they may be beneficial in the maturation and remodelling phase since it
stimulated protein synthesis1
● their short-term benefits may be outweighed by long-term compromise of
the structure and function of the injured tissue2
● they do not take the place of therapeutic modalities and exercise and must
be considered as an adjunct to rehabilitation rather than the most direct
route to recovery2
Cyclooxygenase activity affects healing of many skeletal tissues,
either directly or indirectly through modulation of the inflammatory
response, and pharmacological manipulation of cyclooxygenase can
profoundly affect skeletal health.3
1. Almekinders L. Am JSports Med 1995;23:119-23; 2. Hertel J. J Athletic Training 1997;32:350-358;
3. O’Connor JP & Lysz T. Drugs Today. (Barc.) 2008;44(9):693-709
What is an adverse event?
An Adverse Event (AE) is any untoward medical occurrence in a
patient or clinical trial patient administered an IMP and which does
not necessarily have a causal relationship with this treatment.
The severity was rated by the TAASS investigator as “mild”,
“moderate” or “severe”:
● Mild: transient symptoms, no interference with the patient’s daily
activities
● Moderate: Marked symptoms, moderate interference with the patient’s
daily activities
● Severe: Considerable interference with the patient’s daily activities
A serious adverse event (SAE) is any untoward medical occurrence
that at any dose: results in death, is life threatening, requires
inpatient hospitalization; results in persistent or significant disability /
incapacity; medically important.
What is an adverse drug reaction?
Adverse drug reaction (ADR) is defined as:
● For approved pharmaceutical product: a noxious and unintended
response at doses normally used or tested in humans
The difference between AE and ADR:
● An AE does not imply causality
● An ADR there is a causal link between a drug and an adverse drug
reaction
In summary, an adverse drug reaction is harm directly caused by
the drug at normal doses, during normal use.
No ADRs were reported in this study across all 3 treatment
groups.
Pharmacovigilance data on Traumeel Gel and Ointment report
no ADRs
What about adverse events in the TAASS study?
The majority of events were mild or moderate in severity; none were
serious across all three groups: Traumeel ointment; Traumeel gel;
diclofenac gel
Adverse events (n=43) were reported by 31 of the 447 (6.9%)
patients: at week 6 most adverse events had resolved
Regarding headache, the finding is of no clinical relevance:
● There was no statistical significance between the groups (P = 0.2563)
● None of the events were considered to be related to study medication
● This was well below any incidence reported in the general population
447 patients were included in the safety population, so the low
number of adverse events is confirmation that these are safe
treatments
In general, good safety and tolerability can be assessed for all
three study treatments
The data show that Traumeel is safe and well tolerated
Summary of Adverse Events in the TAASS
Study
In general, good safety and tolerability can be assessed for all three study treatments
Traumeel ointment
N = 152
Adverse Event
Adverse
Events
n
Traumeel gel
N = 148
Patients
Diclofenac gel
N = 147
Adverse
Events
n
n
Patients
Adverse
Events
N
n
Patients
n
Pain
2
1
-
-
-
-
Swelling
-
-
-
-
3
2
Influenza
-
-
1
1
-
-
Nasopharyngitis
-
-
2
2
1
1
Joint injury
1
1
-
-
-
-
Joint sprain
1
1
1
1
1
1
Back pain
-
-
2
2
-
-
Headache
7
3
5
5
1
1
Hypoaesthesia
1
1
-
-
-
-
Oropharyngeal pain
1
1
1
1
1
1
Dry skin
-
-
1
1
-
-
Erythema
4
3
-
-
1
1
Pruritis
2
2
2
2
1
1
Note that a patient may report an adverse event on more than one occasion,
i.e. one patient reported pain on two occasions.
Why was the Orizola study never
published?
The Orizola study was presented at three international congresses
An abstract of the Orizola study has been published in the Official
Journal of the American College of Sports Medicine
The author did not submit the final study to a peer-reviewed
publication
Orizola AJ & Vargas F. Med Sci Sports Med Exerc 2007;39(5Suppl):S79, abstr
858;
Traumeel’s Evidence Base of Efficacy and Safety in
Various Musculoskeletal Conditions - Summary
Study
Musculoskeletal
Conditions
Study type
RCT
Observational
study
√
Efficacy better vs.
placebo
Efficacy equal vs.
NSAIDs
Efficacy better
vs. NSAIDs
Safety vs. NSAIDs
Pain
Mobility
Pain
Pain
Mobility
Equal
√
√
√
√
Zell
et al.
19891
Ankle sprain
Birnesser
et al.
20042
Epicondylitis
√
Schneider
et al.
20053
Tendinopathy
√
√
Schneider
et al.
20084
Musculoskeletal
injuries
√
√
Orizola &
Vargas
20075
Tendinopathy
√
√
Mobility
√
√
1. Zell J et al. Biol Ther. 1989;VII(1):1–6; 2. Birnesser H et al. J Musculoskel Res.
2004;2/3:119–128; 3. Schneider C et al. Explore. 2005;1:446–452; 4. Schneider C, et al.
Complement Ther Med. 2008;16:22–27; 5. Orizola AJ, et al. Med & Sci Sports & Exercise
2007;39 (suppl):S79.
Better
√
√
√
√
√
√
Why are there different study outcomes
between the TAASS and the Orizola studies?
Orizola AJ & Vargas F. Med Sci Sports Med Exerc 2007;39(5Suppl):S79, abstr
858;
Why are there different study outcomes
between the TAASS and the Orizola studies?
The TAASS and Orizola investigated treatment effects in
different indications (ankle sprains and tendinopathies). These
indications are not managed in the same way and the effects
of treatment will differ between these conditions
In order to show superiority in a study like TAASS several
times more patients would have been needed to reach
statistical significance
Orizola AJ & Vargas F. Med Sci Sports Med Exerc 2007;39(5Suppl):S79, abstr
858;
What about blinding in the TAASS study?
Blinded: double-blind refers to both subject and investigator
unaware of the subjects’ treatment; single blind refers to either
subject or investigator unaware of the subject’s treatment; not
always feasible
● The three drug preparations were packed in identical containers,
therefore the investigator in the study was definitely blinded.
● In the TAASS study, randomization was double blind for Traumeel
gel and diclofenac gel, whereby both investigator and subject did
not know what treatment the subject received.
● Randomization was single blind for Traumeel ointment, whereby
the investigator only did not know what treatment the subject
received; while subjects knew that they were receiving ointment,
they did not know which treatment was in the preparation
Are other formulations of Traumeel
available?
Traumeel is available in a variety of formulations for flexibility of use
and to maximize patient convenience and compliance
Traumeel can be obtained in:
● Ointment or gel for topical application
● Oral tablets
● Ampoules of solution for injection
What is the VAS Score?
No pain
Unbearable
pain
0
1
2
3
4
5
6
7
8
9
10
The visual analogue scale (VAS) is a validated tool1,2 and is one of the most widely
accepted measures of pain intensity in pain research
Traumeel ointment and Traumeel gel are both as effective
as diclofenac gel for reducing pain
1. Cox JM. Radiographer April 2005; 52 (5):22;
2. Younger et al. Current Pain and Headache Reports 2009, 13:39–43
What is the VAS Score?
Pain is a difficult outcome to measure; this is due to its multifaceted
and subjective nature.
Self-reporting is essential to overcome the difficulties with
objective measurement of subjective phenomena.
The visual analogue scale (VAS) was devised to measure the amount
of pain that a patient feels ranged across a continuum from none to
unbearable pain.
VAS was used in the TAASS study: a 10cm (100 mm) VAS, starting
with no pain (0 cm/0 mm) and ending with unbearable pain (10
cm/100 mm).
‘The VAS provides a high degree of resolution and is probably the
most sensitive single-item measure for clinical pain research’.1
Traumeel ointment and Traumeel gel are both as effective
as diclofenac gel for reducing pain
1. Cox JM. Radiographer April 2005; 52 (5):22;
2. Younger et al. Current Pain and Headache Reports 2009, 13:39–43
What is the FAAM ADL Score?
The Activities of Daily Living (ADL) subscale of the Foot and Ankle
Ability Measure (FAAM):
● it is a validated tool1
● measures level of function during daily activities of living
● consists of 21 single items, assessing activities of daily living such
as standing, walking, going up stairs, etc.
The scale was standardized to a 0–100 scale, where 100 indicated the
best possible result
Traumeel ointment and Traumeel gel are both as effective as
diclofenac gel for improving function during daily activities of
living
1. Martin R, et al. Foot Ankle Int 2005;26:968–983
What is the “figure-of-eight” method as used
for swelling measurement (i)?
The ‘figure of 8’ method allows the therapist/physician to measure
swelling across the several common sites of ankle sprains. The
procedure is easily reproduced by using bony landmarks about the
ankle1
It is easily administered, requires little equipment, reliable, valid,
and non-time consuming as compared to other methods. For
example, swelling at the ankle joint has been measured by tape
measure and by using callipers across the malleoli (the bony
prominence on each side of the ankle). These methods do not
usually measure swelling resulting from ankle sprains because the
measuring device does not cross the injured structure.
1. Esterson PS. J Orthop Sports Phys Ther. 1979;(1(1):51-2
What is the “figure-of-eight” method as used
for swelling measurement (ii)?
The ‘figure of 8’ method measures ankle circumference as a surrogate
marker of swelling, taking a decrease from baseline as indicative of a
reduction in swelling
Traumeel ointment and Traumeel gel are each as effective as
diclofenac gel for reducing ankle swelling at day 7 of
treatment
Swelling (and also pain) is one of the 5 main signs of
inflammation. Swelling, along with stiffness, is a key symptom
in soft tissue injury. Reducing it is a mark of effectiveness for
any agent
Are there any known drug interactions and
contraindications?
Traumeel may have a lower potential to cause side effects than
diclofenac because unlike NSAIDs, Traumeel has
● no known adverse renal, hepatic, cardiovascular, gastrointestinal
or central nervous system effects
● no known drug interactions
● no contraindications except hypersensitivity
● no risk of tachyphylaxis or addiction with long-term use
● and can be used without caution in children1 and the elderly2
1. Ludwig J, Weiser M. J Biomed Ther 2001: 8-11;
2. Zenner S, Weiser M. Biol Med 1996;25(5):211-6
Summary
Traumeel has been shown to be as effective as diclofenac in a
randomized controlled study (TAASS study), which is a ‘gold standard’
study design
The TAASS study is a significant and robust addition to the evidence
base comparing a natural medicine with a conventional medicine
(diclofenac)
Traumeel ointment and gel is as effective at pain reduction and
improving function as topical NSAIDs, such as diclofenac gel 1%
Traumeel is an effective first-line treatment for patients with
musculoskeletal injury and inflammation
Summary
Traumeel has fewer side effects than NSAIDs
Traumeel can be used in all age groups
Traumeel is better tolerated than NSAIDs
Traumeel is available in tablets, ointment, gel and ampoules, thereby
enabling flexibility of administration
Traumeel’s unique multitargeted, synergistic action addresses
multiple aspects of the inflammatory process.
This unique mechanism of action may promote both tissue repair and
healing, whereas NSAIDs have been proven to have deleterious effect
on healing process in soft tissues
Traumeel is better tolerated than NSAIDs. Another reason to
switch to Traumeel – better tolerability with the added benefit
of a multi-targeted mechanism of action.