Table VI.

Recommendations for points to consider: definition and timing of intervention and comparators

Consideration	Recommendation
1. General	□Optimal time-window for administration of any given intervention should be validated and clearly defined □Assumptions should be avoided; different proposed time-windows for intervention should be tested head to head in feasibility studies if necessary, to ensure patient acceptability, recruitment and likely translation in to clinical care
2. Comparators	□ A comparator and/or placebo or sham arm should always be used where possible ○ Choice will depend on whether study is efficacy or pragmatic ○ Patients should be randomized to intervention or comparator arms ○ Assessment of acceptability of sham treatments, particularly when invasive, is paramount when considering design and feasibility □Double blind protocols should be used where possible □While double-blinding is not always possible, blinded observer/assessor almost always is
3. Multimodality intervention	□ Multi-modality interventions may be particularly suited to this area ○ Such studies are very challenging to design and deliver and require expert input ○ Choice of each component ideally requires a priori evidence of effect □The interaction of different interventions is an important consideration in this area, given that multi-modal intervention is common in clinical practice.