1. How to use Clinical Evidence to inform clinical decision making A case presentation using the CE review on acne

2. History 23-year-old woman, suffering from severe acne on face and back for past 7 years. GP referral Past medical history – acne, low mood for 2 years, links this to acne Family history – nil of note Drug history – oral contraceptive pill, topical benozyl peroxide (not using this at present) Social history – university student, living with friends, non-smoker, moderate alcohol. Acne negatively impacting on social life Case study constructed for purpose of Clinical Evidence demonstration. Not based on any particular individual.

3. Patient’s questions Patient reports feeling depressed, which she believes is linked to the appearance and discomfort of her acne. Recently the severity of her symptoms have worsened, the acne is more difficult to cover with make up, and as a result she is going out less and this is having a negative impact on her social life, studies, and relationship with boyfriend Patient is adamant that she needs a prescription for Roaccutane, as a friend took this and her acne improved Doesn’t want to be ‘palmed off’ with any more ‘creams that never work’. A previous face cream caused redness and itching of her skin. The redness was almost as unsightly as the acne Patient wants the acne to reduce as much as possible, without scarring – plan to look for interventions that will achieve this

4. Consultation structure You explain that you have understood her concerns and you will begin by talking about oral isotretinoin (Roaccutane) as that is what she has requested You will look at the benefits and harms associated with this drug and the evidence behind this information You will discuss how this drug compares with other possible treatments You will think about this drug in the context of other options for acne treatment in order to give her more information with which to make a decision Clinical Evidence can be used to address all these issues…

5. Oral isotretinoin Roaccutane (isotretinoin) In our search we found one RCT comparing isotretinoin versus placebo, and another RCT comparing isotretinoin versus tetracycline, for our outcome of interest, acne severity. Both had small numbers of participants and, when analysed with our GRADE scoring system, provided moderate-quality evidence We have also commented on much larger studies we found, which looked at issues such as teratogenicity, skin adverse effects, liver adverse effects, and psychiatric adverse effects/ suicides. These show that isotretinoin is very teratogenic, it may affect liver markers, may cause dry skin, and they have examined the relationship between isotretinoin and mood disorders and suicide

6. The evidence we have to support our conclusion on oral isotretinoin compared with placebo is of moderate quality In our search, we found one RCT comparing oral isotretinoin with placebo, focusing on our outcomes of interest (one of which is acne severity) This table line summarises the findings from this RCT

7. The RCT we found did not provide any information on these other outcomes of interest The RCT we found comments on adverse effects in the 2 treatment groups but does not provide statistical analysis comparing the groups. Therefore, we cannot comment on whether isotretinoin leads to more adverse effects than placebo from this RCT

8. We found one more RCT of oral isotretinoin that looked at our outcomes of interest. This small RCT compares oral isotretinoin with oral tetracycline. From the table, we can see that oral isotretinoin is favoured over oral tetracycline for reducing acne cysts, pustules and comedones at 24 weeks in this RCT We can refer to the GRADE table in the review to see why this is classed as ‘moderate-quality evidence’. We will see this later

9. This RCT compared adverse effects in people taking oral isotretinoin with people taking oral tetracycline. Although the numbers of people experiencing adverse effects were different in the 2 groups, the RCT did not assess statistical significance, so we cannot comment on which treatment is favoured Here we report absolute numbers, that is how many people had adverse effects in each group

10. We also found some large studies looking at the adverse effects from oral isotretinoin. These issues have been covered in the media and attention has focused on psychiatric adverse effects. Here, we see that the evidence strongly suggests that oral isotretinoin is teratogenic. However, psychiatric adverse effects are more controversial

11. Following on from the Comments section, we have the Clinical guide, putting the evidence we found into an overall clinical context.

12. We have discussed oral isotretinoin, and the patient agrees there are significant risks and limitations to taking it. She would like to see some other options too. This ‘Key Points’ page summarises the treatments for acne. It links to the pages containing evidence for each intervention

13. The categorisation table provides an overview of a range of available treatments and how we have assessed their effectiveness based on randomised controlled trial evidence. It is easy to navigate to the relevant pages for each intervention by clicking on the links Links to the patient leaflets are here These are the clinical questions this review answers

14. Our patient particularly wanted an oral treatment, and we saw from the interventions table that the one oral treatment rated as ‘likely to be beneficial’ was erythromycin After navigating to ‘erythromycin’ we can see the systematic reviews and RCTs undertaken on this drug. Here we see a comparison with tetracycline

15. Here we see that tetracycline is rated as ‘Trade off between benefits and harms’. To find out more about this particular case, click on tetracycline To find out more about what this classification means, click on the icon

16. It would be interesting to know how erythromycin compared with placebo. We found no RCTs on this

17. The GRADE table. Here, we can see how the GRADE classifications are decided. For example, oral erythromycin versus oral tetracycline for acne severity is rated as low-quality evidence 4 points are given for RCT evidence Here we can see why points were deducted

18. Conclusions We have looked at the evidence for the benefits and harms of a treatment the patient requested We have compared this intervention with others in terms of benefits and harms, and assessed the quality of evidence behind these We have been able to provide the patient with more knowledge of the range of available interventions, as well as the pros and cons of each We have been able to see where gaps in the current evidence base are