SUMMARY – CASP appraisal tool

Talsma

LEVEL 2

116 PATIENTS, 6 MONTH EXPERIMENT, 12-MONTH FOLLOW UP, ALMOST 50/50 GENDER SPLIT, AVERAGE AGE 19
YEARS

LOW DOSE GROUP (CUMULATIVE DOSE 170MG/KG) RELAPSE RATE 43.8% – HIGH DOSE GROUP (310 MG/KG)
RELAPSE RATE 26.6%

SATISFIED AFTER TREATMENT? 42.3% OF LOW DOSE GROUP WERE PRESCRIBED ANOTHER MEDICATION, WHILE
28.1% OF THE HIGH DOSE SOUGHT FURTHER TREATMENT. THIS SHOWS THAT AS WELL AS HAVING A HIGHER
RELAPSE RATE, THE LOW DOSE GROUP WERE MORE LIKELY TO ATTEMPT ANOTHER ROUND OF TREATMENT.

HIGHER DOSE GROUP SAW MORESIDE EFFECTS SUCH AS INFLAMMED LIPS AND DRY SKIN.

Sardana

COMPARING LOW DOSE (0.5 MG/KG/DAY) = (90MG/KG/6 MONTHS) TO STANDARD DOSE (1MG/KG/DAY) =
(CUMULATIVE DOSE 180MG/KG/6 MONTHS)

THIS STUDY’S STANDARD DOSE WAS LIKE THE TALSMA’S LOW DOSE

LEVEL 1 – SYSTEMATIC REVIEW

THE REASON I CHOSE THIS WAS TO SEE IF SMALLER DOSES THAN THE ‘LOW-DOSE’ IN TALSMA’S STUDY COULD
POTENTIALLY HAVE A BETTER EFFECT WHEN ADMINISTERED OVER A LONGER PERIOD. SO INSTEAD OF JUMPING TO
HIGH DOSE FOR 6 MONTHS (AS THIS WAS FAVOURED IN THE FIRST STUDY), I WAS CONSIDERED A LOWER DOSAGE
FOR A LONGER TIME.

18 STUDIES COMPARING LOW DOSE TO STANDARD FOUND NO SIGNIFICANT DIFFERENCES IN EFFICACY.

AUTHORS STATED THAT LIMITATIONS TO THEIR RESEARCH INCLUDED INCONSISTENT VARIABLES SUCH AS AGE, SEX,
DURATION, HEALTH CONDITIONS (PCOS)
AND FOLLOW UP TIMES.

Sadeg

LEVEL 1

15 RELATED STUDIES

ONE STUDY FOUND 0.5-0.7MG/KG DAILY FOR 6 MONTHS HAD A RELAPSE RATE OF 13%, WHILE LOWER DOSEAGE
(0.25-0.4 MG/KG/DAILY) HAD A RELAPSE RATE OF 18%.

THE SAME STUDY ADDED A 3RD GROUP TO EXAMINE IF TREATMENT 1 WEEK ON, 3 WEEKS OFF FOR 6 MONTHS
WOULD BE BENEFICIAL, AND FOUND A 56% RELAPSE RATE.

AVERAGE AGE WAS 22, MAJORITY WOMEN.

ALSO CONCLUDED THAT DOSAGES LOWER THAN 0.5MG/KG/DAILY FOUND NO DIFFERENCE TO STANDARD
TREATMENTS.

 INTRODUCE CASE STUDY

Good afternoon,

So, my case study for this assessment involved a 25-year-old female, named Jane, who has been suffering
from severe acne for almost a decade. The aim of my research is to find the best available evidence to
determine if low-dose oral isotretinoin is more effective then high-dose oral isotretinoin for treating Jane’s
condition long-term. The evidence gathered found that the treatment was effective in most cases
regardless of dosage, however, higher-dose treatments resulted in lower relapse rates compared to those
given the low-dose treatment.

Reflecting on feedback of Part A of this assessment, I will also be discussing the importance of high levels
of evidence, as well as why the quality of the study influences my professional recommendations.

 ASSESS BODY OF EVIDENCE (ACCORDING TO NHMRC GUIDELINES)

EVIDENCE BASE (QUANTITY, LEVEL, QUALITY)

Referring to the table in the summary, the three chosen sources have been analysed and graded for their
evidence base, consistency, and clinical impact. All sources were rated either good or excellent according
to the National Health and Medical Research Council body of evidence matrix, however it was difficult to
find many studies which matched the clinical question more accurately.

Firstly, the evidence base of all sources was rated high as the systematic reviews both involved over 15
studies slightly related to the question, and the RCT in the first study was a single study but involved a
similar population to that in my case study.

All sources were ranked either level 1 or level 2 according to the NHMRC guidelines, meaning they contain
the most reliable data in comparison to other levels of evidence, which is essential for evidence based
practice. Being systematic reviews of level 2 evidence, the level 1 sources provided a broad range of
information regarding different dosages and sample sizes, however my main focus was on the single RCT in
2013.

The overall quality for the systematic reviews was low due to factors which affect risk of bias such as
different ages, sex, follow up period, duration, lifestyle changes during the experiment, skin care routines,
and other personal factors. My recommendations were definitely influences by the lack of consistency,
however I focused on factors which related to my case and adjusted my opinion accordingly. The currency
of the reviewed studies also affects the quality of the evidence, as there were few systematic reviews for
this topic done in the past decade.

CONSISTENCY

The consistency of results throughout the studies was quite high, with researchers mainly finding that
cumulative doses higher than 310mg/kg were more effective than the standard treatment, however
comparing the standard treatment to even lower doses did not see any significant differences. Most
studies also reported that the lower the dose, the lower the rate of participants experiencing side effects,
however this was not the case in all studies.

CLINICAL IMPACT
The NHMRC states that factors such as relevance to the clinical question, duration of treatments, and risks
and benefits must be considered when assessing this section. All 3 sources demonstrate a relatively high
clinical impact as they all provide data on the efficacy of treatment options for a similar population group.
The duration of the treatments from the different studies were also used as a guideline for my clinical
recommendation which will be discussed later, and the studies also gave important insight on side effects
which would be discussed with the patient.

Overall, I have graded the sources as B, B, and C respectively to how they are on the table. This helps
indicate the level of influence they have on my clinical recommendation.

 COMPARE AND CONTRAST EVIDENCE FROM ALL SOURCES

The main difference between the Talsma’s single study RCT and the other 2 systematic reviews, was that
the RCT tested for significantly higher concentrations of isotretinoin. The cumulative low-dose in this 6-
month study was around 170mg/kg, which was considered the standard or high dose in all other reviewed
studies. After a suitable follow-up period of 12 months, the researcher found the relapse rate of the low-
dose group was roughly 44%, compared to 27% in the high-dose group. This finding alone supported my
recommendation of prescribing a higher-dose as my patient’s main concern is her acne returning, however
the greater risk of side effects will definitely be discussed beforehand.

Comparing this to the other 2 sources, the duration, sample size, follow-up period, and dosages which
were classified as low or high all differed, however the findings all demonstrated very similar results. For
example, a 2001 study reviewed in the 2020 systematic review found that micro dosing isotretinoin at
0.4mg/kg without food once daily, compared to 0.1mg/kg with food twice daily found almost identical
results after 5 months of treatment. Even though this study compared micro dosages, similar results were
found in the 2010 systematic review, where they compared 18 studies and concluded that the efficacy was
not drastically different between either treatment plans. (Low dose was anything below 0.5mg/kg/daily,
standard was 1mg/kg/daily.

In regards to relapse, the similarities between all 3 sources were that patients who were administered
lower cumulative doses had a higher chance of their acne returning, but this was also influenced by other
biological factors such as gender, age, polycystic ovarian disease, and pre-existing dermatitis.

APPLY TO CLIENT

After reviewing all results which were fitting to my case study, I noted a few things that would assist in
applying this to my client’s case.

Firstly, as a health professional, I will be prioritising the patient’s wellbeing as it is clear the side effects of
isotretinoin can be quite severe. Although the majority of cases in the 3 articles found that standard
dosages did not produce any drastic side effects which impacted daily functioning, I will be discussing the
potential risks with my client and carrying out monthly check-ups.

In regards to my final clinical recommendation, I have amended this from Part A. Based on my client’s
weight of 60kg, a cumulative dose of 200mg/kg over 7 months will be the best treatment. This will involve
4 months taking 40mg once daily, followed by 3 months of 60mg once daily. This can be modified at any
time if the client advises of any adverse side effects, however, it is recommended that the treatment is
completed for the recommended duration even if they are happy with results, in order to prevent relapse.

 ESTIMATE CLINICAL EFFECT SIZE AND RANGE OF EFFECT IN STUDIES

It was difficult to determine the range of effect as the studies in the systematic reviews yielded different
results based on different dosages and durations of treatments. However, in Talsma’s RCT, the effect size
of the relapse rate for the lower-dose group can be described as a relative risk of 1.6, in comparison to the
higher-dosage group. The statistics for which group improved the most were not given but the relapse rate
was more important for my case study regardless.

RR – COMPARES RISK IN ONE GROUP FROM ANOTHER, DIVIDES THE RISK IN GROUP 1 TO GROUP 2

The clinical effect size for this intervention is estimated to be large as the medication has been proven its
effectiveness in all studies. The only concern is post-treatment conditions, as the skin condition may
return. Although it may not return to its original severity, going backwards may influence the client’s
happiness, resulting in a subjective effect size.

 CLIENT’S MINIMAL IMPORTANT DIFFERENCE (MID) FOR THE INTERVENTION?

My client’s current satisfaction with her skin is very low, and self-reported a score of 1/10. We would
expect to see a significant improvement within the first few months of treatment, and hopefully after the 7
months, the client’s MID will be at least 6/10. Due to her condition being quite severe, things like scarring
and pigmentation may still be quite evident, however these can be improved after reducing her active
acne. The medication is taken once daily which does not impact her routine, however, things such as dry
skin, nose bleeds, and joint pain should be considered as they could possibly affect daily tasks. It is also
good to note that this treatment is very cost effective, especially in comparison to cosmetic procedures
and skin care products which the client previously tried.

 HOW DOES THE EFFECT SIZE COMPARE TO THE MID?

As the effect size is estimated to be a large improvement in the client’s current skin condition, this is will
likely be shown in their minimal importance difference too. The treatment is moderate risk and will only be
taken for 7 months, which I believe is an appropriate plan in order to see such great results.

 WHAT IMPLICATIONS DOES THIS HAVE FOR YOUR CLIENT?

The research papers all state that higher concentrations of this medication were linked to the increased
risks of side effects such as: dry skin, dry lips, headaches, elevated liver enzymes, gastrointestinal
inflammation, nose bleeds, joint pain, and hair loss. Because of this, monthly check-ups are essential and
although the client reported they do not drink regularly, it is recommended alcohol is completely avoided
during the treatment, as the liver is already under enough stress due to the medication.

In addition to this, I will need to discuss forms of birth control if the client is sexually active, as this
medication is known to cause fetal abnormalities during pregnancy. This is a very important consideration
for both client and health professional as if there were plans to fall pregnant, another recommendation
must be made.

 OTHER ICF CONTEXUAL FACTORS TO BE CONSIDERED?

My client’s obvious goal is to reduce her acne and feel more confident in her skin as she stated it has now
begun to affect her social life. This treatment plan aims to achieve this while not producing any serious side
effects which will dramatically impact her personal or professional life. My client lives a very active and
healthy lifestyle, so keeping track of her recovery after training and any dramatic changes in eating habits
or moods can be beneficial as the medication could potentially impact these areas. The only other
consideration which my client expressed was a high value was a non-hormonal treatment, which this
medication is not.

 HOW MIGHT YOU COMMUNICATE YOUR EVIDENCE-BASED REASONING RECOMMENDATIONS

TO YOUR CLIENT? SHARED DECISION MAKING

My next consultation with my client will start by discussing my initial recommendation of treatment plan,
followed by the possible risks and side effects. I will also provide insight on the effectiveness in past
studies, as well as what dosage options were were shown to have lower relapse rates. Expectations post-
treatment will also be discussed as relapse is highly dependent on the individual but another round of
medication is also an option. I will mention that there are multiple other options, and ask the client if they
wish for me to discuss these further.

I will ask questions in relation to birth control, past history with depression, and if monthly check-ups were
maintainable with her schedule. I will also make sure to ask the client if they have any specific concerns
regarding the medication, and they completely understand how/when to take it, as well as provide
assistant to discover alternative options if necessary. If the client is happy with the recommended
treatment plan, then medication will be prescribed and regular contact will be made to ensure they are on
track.