Netherlands Journal

netherlands journal of critical care
Table 5: Opportunities and threats as indicated by the participants.
Opportunities
Spontaneously mentioned
by:
Threats
Spontaneously mentioned
by:
Increasing Candida-infections 2 Highly effective other treatments at low side 1
effects
Increasing drug-resistance 2 Uncertainty surrounding issue of Candida-infections
1
Many complex clinical situations for use 2 New, other, expensive drugs 2
Toxicity of other anti-fungals 1 Late toxicity 2
Current therapy imperfect 1 Budget issues 2
More immune compromised patients (HIV, Cancer, 5 Development of resistance 1
transplant)
Rapid cure (cost-reduction, HLOS) 1 Not cost effective 1
Aspergillosis 1 Scepticism 2
Non-infectious indications 1 Insufficient clinical data 1
Patients request more therapies 1 Negative effects on bacterial infections 1
Better survival 1 Difficult clinical studies 3
Jumping the gun 2
Table 6: Scoring of the opportunities listed in Table 5 (0=unimportant, 10=of great importance).
Opportunities 1 2 3 4 5 6 7 8 Avg SD Ranking
More immune compromised patients (HIV, Cancer, transplant)
8 9 9 8 10 9 9 9 8,9 0,6 1
Increasing Candida-infections 10 8 8 6 10 9 9 10 8,8 1,4 2
Better survival 8 8 9 9 8 9 8 9 8,5 0,5 3
Rapid cure (cost-reduction, HLOS) 6 9 9 8 10 8 9 9 8,5 1,2 4
Increasing drug-resistance 10 8 4 6 10 9 9 10 8,3 2,2 5
Current therapy imperfect 8 8 8 8 4 8 9 9 7,8 1,6 6
Many complex clinical situations for use 10 9 9 7 5 5 7 8 7,5 1,9 7
Aspergillosis 8 8 5 6 10 5 7 8 7,1 1,7 8
Toxicity of other anti-fungals 6 7 4 7 8 6 9 9 7,0 1,7 9
Patients request more therapies 0 7 9 5 0 9 6 2 4,8 3,7 10
Non-infectious indications 0 7 4 7 2 2 6 5 4,1 2,6 11
The overall average of the strengths was 7,3 points, with a median of
8,0. The promising initial clinical data (in spite of the fact that the full
results of the study discussed at the meeting had not yet been published)
was regarded as the most important strength, with an average
of 8,4 points. The novel mechanism of action and the favourable
safety profile of Mycograb were also viewed as important strengths,
with 8 and 7,9 points, respectively. The synergism with other antifungal
drugs received only 5,3 points, with judgments ranging from 0 to
10 points. This was explained by the participants who gave low marks
as an expression of “you need more than one drug, i.e. you are adding
a very expensive drug that still can’t do the job alone”; whereas the
participants who gave high marks for this issue regarded the fact that
lower doses of potentially toxic drugs would perhaps be required,
and the synergy between fungistatic/fungicide drugs and HSP90 inhibition
as potentially very valuable. Finally, the novel mechanism of
action (targeting HSP90) and the physiological concepts underlying
this novel treatment and “line of attack” were viewed as significant
strengths, at 7,7 points.
The average score for the potential weaknesses of Mycograb was
7,9 (median 7,8) points. The expected high price was regarded as the
most important potential weakness of Mycograb. When asked why
these scores were so high in spite of the previous comments that any
efficacious treatment would probably find its way to the clinic anyway,
the participants remarked that because there is so far little absolute
proof from large well-designed studies of Mycograbs’ efficacy, and
the participants expect that the expected costs may therefore hamper
the widespread usage of the new drug.
The fact that initially significant differences in mortality associated
with Mycograb use had disappeared after three months in the
study by Pachl et al. (50) was also regarded as an important weakness
by the participants, with 8,3 points. The fact that total “Candida attributable
mortality” was relatively low further complicates the interpretation
of the results of this study.
Overall, the novel mechanism of action, the absence of significant
side effects combined with its efficacy was viewed as the most important
strength of Mycograb by most participants.
Almost all participants also regarded the broad spectrum as an
important advantage. The most significant problem was the potentially
high price and lack of large amounts of clinical evidence for ts
efficacy.
After this discussion the participants focussed their attention on external
factors, by assessing and scoring opportunities and threats for
the use Mycograb. The results are shown in tables 5, 6 and 7.
The overall average of all the opportunities was 7,4 points (median
8,0 points); for the threats the average was 7,0 (median 7,0 points).
The increasing number of immune-compromised patients admitted
to the ICU (8,9 points) as well as the rising number of Candida
infections in the ICU (8,8 points) were viewed as the most important
opportunities for Mycograb. The reported increase in survival (in
spite of the discussion outlined above) was also viewed as an important
opportunity, as was the speeding up of cure rates in the study
by Pachl et al. (50). The increase in drug resistance was also viewed
as an important opportunity. Indeed only the items “non-infectious
592
neth j crit care • volume 10 • no 5 • october 2006