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21/539 Benefits and harms of maintenance therapy for refractory acne vulgaris or previous relapses by reduced dose isotretinoin regimens

Contents

Introduction

The aim of the Health Technology Assessment (HTA) Programme is to ensure that high quality research information on the clinical effectiveness, cost-effectiveness and broader impact of healthcare treatments and tests are produced in the most efficient way for those who plan, provide or receive care from NHS and social care services. The commissioned workstream invites applications in response to calls for research on specific questions which have been identified and prioritised for their importance to the NHS, patients and social care.

Research question

In people with refractory acne vulgaris and/or recurrent relapses, what are the benefits and harms of reduced dose oral isotretinoin maintenance therapy?  

  1. Intervention: Reduced dose of oral isotretinoin regimens (e.g. less than 0.5mg/kg; weekly or bi-weekly dosage regimens; Applicants to define and justify).
  2. Patient groups: (i) People with refractory acne vulgaris despite previous treatment courses with standard daily dose oral isotretinoin; and/or (ii) people with cleared acne who require maintenance treatment due to previous relapses. (Applicants to define and justify). Applications are encouraged which include recruitment from geographic populations with high disease burden which have been historically underserved by research activity in this field.
  3. Setting: Dermatology clinics.
  4. Comparator(s): To be defined and justified by Applicants, e.g. comparators suggested by NICE (standard daily dose of isotretinoin; treatment that includes an oral antibiotic).
  5. Study design: A randomised controlled trial with an internal pilot phase to test key trial processes such as recruitment and adherence. Clear stop/go criteria should be provided to inform progression from pilot to full trial. Applicants to consider the influence of blinding and routine protocols, e.g. titration.
  6. Important outcomes: Clinician reported improvement, including change in acne lesion count; patient reported improvement; adverse effects (including, but not limited to, mucosal / cutaneous changes; change in mood; new psychiatric diagnosis; suicidality). Existing Core Outcomes should be included amongst the list of outcomes, unless a good rationale is provided to do otherwise.
  7. Other outcomes: Recurrence; adherence of treatment regimen (including reasons for non-adherence or discontinuation); patient and parent/carer experience and acceptability. Patient-reported outcomes should be reported by sex and gender. Applicants should clearly define and justify their criteria of measuring 'relapse'.
  8. Minimum duration of follow-up: 12 months intervention, followed by 12 months follow-up.
  9. Longer-term follow up: If appropriate, researchers should consider obtaining consent from participants to allow potential future follow up through efficient means (such as routine data) as part of a separately funded study.

Rationale

Acne vulgaris is a common condition that can affect the face, chest and back. It is most prevalent among adolescents and young adults, affecting approximately 80% of people at some time between 11 and 30 years of age. When treating acne vulgaris, its severity, distribution, and the views of the affected person, need to be taken into account. The aim of treatment is to reduce the amount of skin lesions and to prevent recurrence and scarring.

Oral isotretinoin is prescribed for severe forms of acne vulgaris resistant to adequate courses of standard therapy with systemic antibacterials and topical therapy. The drug is highly effective, but has the potential to cause a number of serious adverse effects, including psychiatric effects and severe or life-threatening harm to an unborn child. Strict guidelines issued by the Medicines & Healthcare products Regulatory Agency (MHRA) require that isotretinoin can be prescribed only under the supervision of a consultant dermatologist; and patients with childbearing potential must follow a pregnancy prevention programme.

The daily dose of isotretinoin typically ranges between 0.5mg to 1mg/kg; however, dosage adjustments may be required for people with severe intolerances or those at higher risk of developing serious adverse effects. There is only limited high-quality data on the effectiveness and optimum treatment duration of reduced (less than 0.5mg/kg) daily dose isotretinoin in acne vulgaris. Furthermore, there have been reports of the successful use of weekly (mini) and bi-weekly (micro) isotretinoin regimens for people with recurrent relapse despite adequate response to previous courses of isotretinoin. However, the evidence for these regimens is limited to case series and small cohort studies.

The NICE Guideline Committee (Acne Vulgaris: Management, GID-NG10109, in development) concluded that further research will help to establish if reduced dose regimens of oral isotretinoin are effective in the maintenance treatment of people who have recurrent relapses of acne vulgaris despite previous treatment courses with standard daily dose oral isotretinoin, and the optimum duration of maintenance treatment.

The HTA programme wishes to fund the study outlined above to inform clinical practice, patient choice, and future guideline updates.

A separate call is available for reduced daily dose oral isotretinoin in the management of acne vulgaris. Applicants should consider whether synergies between the two calls offer opportunities for efficiency, and we would welcome applicants to propose shared infrastructure between the two calls.

Additional commissioning brief background information

A background document is available that provides further information to support applicants for this call. It is intended to summarise what prompted the call and the existing evidence base, including relevant work from the HTA and wider NIHR research portfolio. It was researched and written on the basis of information from a search of relevant sources and databases, and in consultation with a number of experts in the field. If you would like a copy please email htaresearchers@nihr.ac.uk.

Making an application

If you wish to submit a Stage 1 application for this call, the online application form can be found on the Funding opportunities page.  To select this call, use the filters on the right of the screen or search using the call name and/or number.

Your application must be submitted on-line no later than 1pm on the 1 December 2021. Applications will be considered by the HTA Funding Committee at its meeting in January 2022.

Guidance notes and supporting information for HTA Programme applications are available by clicking the links.

Important: Shortlisted Stage 1 applicants will be given eight weeks to submit a Stage 2 application. The Stage 2 application will be considered at the Funding Committee in May 2022.

Applications received electronically after 1300 hours on the due date will not be considered.

For commissioned topics, the Programme strongly discourages the practice of the same co-applicant joining more than one competing team. There may be unusual circumstances where the same person could be included on more than on application eg a lead from a named charity or a unique national expert in a condition. For such exceptions (i) each application needs to state the case as to why the same person is included (ii) the shared co-applicant should not divulge application details between teams and (iii) both teams should acknowledge in their application that they are aware that one of their co-applicants is part of a competing application and that study details have not been shared. 

Should you have any queries please contact us by email: htacommissioning@nihr.ac.uk.