Guidance

Recommendations for research

Recommendations for research

The 2011 Guideline Development Group has made the following recommendations for research, based on its review of evidence, to improve NICE guidance and patient care in the future. The Guideline Development Group's full set of recommendations for research is detailed in the full guideline.

1 A comparison of the clinical and cost effectiveness of sertraline and CBT in people with GAD that has not responded to guided self-help and psychoeducation

What is the relative effectiveness of sertraline compared with cognitive behavioural therapy (CBT) in people with generalised anxiety disorder (GAD) that has not responded to guided self-help and psychoeducation in a stepped-care model?

This question should be addressed using a randomised controlled design in which people with GAD that has not responded to step 2 interventions are allocated openly to treatment with sertraline, CBT or waiting-list control for 12 to 16 weeks. The control group is important to demonstrate that the 2 active treatments produce effects greater than those of natural remission. The period of waiting-list control is the standard length of CBT treatment for GAD and is also commonly the length of time that it would take for specialist CBT to become available in routine practice. After 12 to 16 weeks all participants should receive further treatment chosen in collaboration with their treating clinicians.

The outcomes chosen at 12 to 16 weeks should include both observer- and participant-rated measures of clinical symptoms and functioning specific to GAD, and of quality of life. An economic analysis should also be carried out alongside the trial. The trial needs to be large enough to determine the presence or absence of clinically important effects and of any differences in costs between the treatment options using a non-inferiority design. Mediators and moderators of response should be investigated. Follow-up assessments should continue over the next 2 years to ascertain whether short-term benefits are maintained and, in particular, whether CBT produces a better long-term outcome.

Why this is important

Both sertraline and CBT are efficacious in the treatment of GAD but their relative efficacy has not been compared. In a stepped-care model both CBT and sertraline are treatment options if step 2 interventions (guided self-help and/or psychoeducation) have not resulted in a satisfactory clinical response. At present, however, there are no randomised trial data to help prioritise next-step treatments and no information on how individuals with GAD may be matched to particular therapies. Clarification of the relative short- and longer-term benefits of sertraline and CBT would be helpful in guiding treatment.

2 The clinical and cost effectiveness of 2 CBT-based low-intensity interventions (CCBT and guided bibliotherapy) compared with a waiting-list control for the treatment of GAD

In well-defined GAD, what is the clinical and cost effectiveness of 2 CBT-based low-intensity interventions (computerised cognitive behavioural therapy [CCBT] and guided bibliotherapy) compared with a waiting-list control?

This question should be answered using a 3‑armed randomised controlled design using both short- and medium-term outcomes (including cost-effectiveness outcomes). Particular attention should be paid to the reproducibility of the treatment model with regard to content, duration and the training and supervision of those delivering interventions to ensure that the results are both robust and generalisable. The outcomes chosen should include both observer- and participant-rated measures of clinical symptoms and functioning specific to GAD, and an assessment of the acceptability and accessibility of the treatment options.

Why this is important

Psychological treatments are a recommended therapeutic option for people with GAD. CCBT is a promising low-intensity intervention for GAD that does not yet have a substantial evidence base. It is therefore important to establish whether CCBT is an effective and cost-effective treatment that should be provided for GAD, and how it compares with other low-intensity interventions such as guided bibliotherapy. The results of this trial will have important implications for the provision, accessibility and acceptability of psychological treatment in the NHS.

3 The effectiveness of physical activity compared with waiting-list control for the treatment of GAD

For people with GAD who are ready to start a low-intensity intervention, what is the clinical effectiveness of physical activity compared with waiting-list control?

This question should be answered using a randomised controlled design for people with GAD who have been educated about the disorder (as described in step 1) and are stepping up to a low-intensity intervention. The period of waiting-list control should be 12 weeks. The outcomes chosen should include both observer- and participant-rated measures of clinical symptoms and functioning specific to GAD, and of quality of life.

Why this is important

The evidence base for the effectiveness of physical activity in reducing anxiety symptoms is substantially smaller than that for depression. However, where evidence exists there are signs that physical activity could help to reduce anxiety. As GAD is a commonly experienced mental health disorder the results of this study will have important implications in widening the range of treatment options available in the NHS.

4 The effectiveness of chamomile and ginkgo biloba in the treatment of GAD

Is chamomile/ginkgo biloba more effective than placebo in increasing response and remission rates and decreasing anxiety ratings for people with GAD?

This question should be addressed using a placebo-controlled, double-blind randomised design to compare the effects of a standardised dose of chamomile (220 mg to 1100 mg) or ginkgo biloba (30 mg to 500 mg) in a readily available form, for example a capsule, with placebo. This should assess outcomes at the end of the trial and at 12-month post-trial follow-up. The outcomes chosen should include both observer- and participant-rated measures of clinical symptoms and functioning specific to GAD, and of side effects. There should be a health economic evaluation included and an assessment of quality of life. The trial should be large enough to determine the presence or absence of clinically important effects using a non-inferiority design. Mediators and moderators of response should be investigated.

Why this is important

GAD is a common mental health disorder and the results of this study will be generalisable to a large number of people. There is evidence for the efficacy of chamomile and ginkgo biloba in reducing anxiety in people with GAD but the evidence base is small (1 study). However, the scarce literature on the effectiveness of other herbal interventions for treating GAD points to chamomile and ginkgo biloba as 2 of the more effective herbal interventions. Moreover, both these herbal remedies are widely available and relatively inexpensive. Furthermore, at present there is no scientific evidence of side effects or drug–herbal interactions in relation to chamomile or ginkgo biloba. As both these herbal interventions are readily available and have no known side effects, they could be used at an early stage as a means of preventing progression to drug treatments, which are associated with a number of undesirable side effects and dependency.

5 The clinical and cost effectiveness of a primary care-based collaborative care approach to improving the treatment of GAD compared with usual care

What are the benefits of a primary care-based collaborative care approach to improving the treatment of GAD compared with usual care?

This question should be addressed using a cluster randomised controlled design in which the clusters are GP practices and people with GAD are recruited following screening of consecutive attenders at participating GP practices. GPs in intervention practices should receive training in recognising GAD and providing both drug treatment and GP-delivered low-intensity psychological interventions (psychoeducation and non-facilitated self-help). Psychological wellbeing practitioners in intervention practices should provide these low-intensity psychological interventions and support GP-prescribed drug treatment by providing information about side effects, monitoring medication use and liaising about any changes to medication. They should also support the referral for CBT of participants whose symptoms have not improved following low-intensity interventions. Structured, practice-based protocols should define care pathways, the interventions to be provided by practitioners at each point in the care pathway and the mechanisms they should use to liaise about individual patients. In control practices, participants should receive care as usual from the GP, including referral for primary and secondary care psychological interventions or mental health services.

Outcomes should be evaluated at 6 months with follow-up assessments continuing for up to 2 years to establish whether short-term benefits are maintained in the longer term. The outcomes chosen should include both observer- and participant-rated measures of clinical symptoms and functioning specific to GAD, and of quality of life. An economic analysis should also be carried out alongside the trial. The trial needs to be large enough to determine the presence or absence of clinically important effects and of any differences in costs between collaborative care and usual care.

Why this is important

Most people with GAD in the UK do not receive evidence-based management and poor recognition of GAD by GPs contributes to a lack of appropriate interventions being offered. There is some evidence that complex interventions involving the training of primary care practitioners, together with a collaborative care approach involving GPs, other primary care practitioners and mental health professionals, can improve the uptake of evidence-based interventions and clinical and functional outcomes for people with GAD. However, these approaches have not been evaluated in primary care in the UK. Given the differences between the organisation of primary care in different countries, such as the US, it is important to demonstrate whether these approaches can also be effective in the UK.

6 The clinical and cost effectiveness of 2 CBT-based low-intensity interventions (CCBT and guided bibliotherapy) compared with a waiting-list control for the treatment of panic disorder

In well-defined panic disorder, what is the clinical and cost effectiveness of 2 CBT-based low-intensity interventions (CCBT and guided bibliotherapy) compared with a waiting-list control?

This question should be answered using a 3‑armed randomised controlled design using both short- and medium-term outcomes (including cost-effectiveness outcomes). Particular attention should be paid to the reproducibility of the treatment model with regard to content, duration and the training and supervision of those delivering interventions to ensure that the results are both robust and generalisable. The outcomes chosen should include both observer- and participant-rated measures of clinical symptoms and functioning specific to panic disorder, and an assessment of the acceptability and accessibility of the treatment options.

Why this is important

Psychological treatments are a recommended therapeutic option for people with panic disorder. CCBT is a promising low-intensity intervention for panic disorder that does not yet have a substantial evidence base. It is therefore important to establish whether CCBT is an effective and cost-effective treatment that should be provided for panic disorder, and how it compares with other low-intensity interventions such as guided bibliotherapy. The results of this trial will have important implications for the provision, accessibility and acceptability of psychological treatment in the NHS.