Advancing novel therapies for neurodegeneration through an innovative model for industry-academia collaborations: A decade of the Eisai-UCL experience.

External innovation initiatives in the pharmaceutical industry have become an integral part of research and development. Collaborations have been built to enhance innovation, mitigate risk, and share cost, especially for neurodegenerative diseases, a therapeutic area that has suffered from high attrition rates. This article outlines the Eisai-University College London (UCL) Drug Discovery and Development Collaboration as a case study of how to implement a productive industry-academic partnership. In the first 10 years, seven projects have been established and the first project, a novel anti-tau antibody for Alzheimer's disease, has entered clinical trials, providing early validation of this collaboration model.

Clinical effectiveness and cost-effectiveness of cognitive behavioural therapy as an adjunct to pharmacotherapy for treatment-resistant depression in primary care: the CoBalT randomised controlled trial.

BACKGROUND: Only one-third of patients with depression respond fully to treatment with antidepressant medication. However, there is little robust evidence to guide the management of those whose symptoms are 'treatment resistant'. OBJECTIVE: The CoBalT trial examined the clinical effectiveness and cost-effectiveness of cognitive behavioural therapy (CBT) as an adjunct to usual care (including pharmacotherapy) for primary care patients with treatment-resistant depression (TRD) compared with usual care alone. DESIGN: Pragmatic, multicentre individually randomised controlled trial with follow-up at 3, 6, 9 and 12 months. A subset took part in a qualitative study investigating views and experiences of CBT, reasons for completing/not completing therapy, and usual care for TRD. SETTING: General practices in Bristol, Exeter and Glasgow, and surrounding areas. PARTICIPANTS: Patients aged 18-75 years who had TRD [on antidepressants for ≥ 6 weeks, had adhered to medication, Beck Depression Inventory, 2nd version (BDI-II) score of ≥ 14 and fulfilled the International Classification of Diseases and Related Health Problems, Tenth edition criteria for depression]. Individuals were excluded who (1) had bipolar disorder/psychosis or major alcohol/substance abuse problems; (2) were unable to complete the questionnaires; or (3) were pregnant, as were those currently receiving CBT/other psychotherapy/secondary care for depression, or who had received CBT in the past 3 years. INTERVENTIONS: Participants were randomised, using a computer-generated code, to usual care or CBT (12-18 sessions) in addition to usual care. MAIN OUTCOME MEASURES: The primary outcome was 'response', defined as ≥ 50% reduction in depressive symptoms (BDI-II score) at 6 months compared with baseline. Secondary outcomes included BDI-II score as a continuous variable, remission of symptoms (BDI-II score of < 10), quality of life, anxiety and antidepressant use at 6 and 12 months. Data on health and social care use, personal costs, and time off work were collected at 6 and 12 months. Costs from these three perspectives were reported using a cost-consequence analysis. A cost-utility analysis compared health and social care costs with quality adjusted life-years. RESULTS: A total of 469 patients were randomised (intervention: n = 234; usual care: n = 235), with 422 participants (90%) and 396 (84%) followed up at 6 and 12 months. Ninety-five participants (46.1%) in the intervention group met criteria for 'response' at 6 months compared with 46 (21.6%) in the usual-care group {odds ratio [OR] 3.26 [95% confidence interval (CI) 2.10 to 5.06], p < 0.001}. In repeated measures analyses using data from 6 and 12 months, the OR for 'response' was 2.89 (95% CI 2.03 to 4.10, p < 0.001) and for a secondary 'remission' outcome (BDI-II score of < 10) 2.74 (95% CI 1.82 to 4.13, p < 0.001). The mean cost of CBT per participant was £ 910, the incremental health and social care cost £ 850, the incremental QALY gain 0.057 and incremental cost-effectiveness ratio £ 14,911. Forty participants were interviewed. Patients described CBT as challenging but helping them to manage their depression; listed social, emotional and practical reasons for not completing treatment; and described usual care as mainly taking medication. CONCLUSIONS: Among patients who have not responded to antidepressants, augmenting usual care with CBT is effective in reducing depressive symptoms, and these effects, including outcomes reflecting remission, are maintained over 12 months. The intervention was cost-effective based on the National Institute for Health and Care Excellence threshold. Patients may experience CBT as difficult but effective. Further research should evaluate long-term effectiveness, as this would have major implications for the recommended treatment of depression. TRIAL REGISTRATION: Current Controlled Trials ISRCTN38231611.

Why do GPs exclude patients from participating in research? An exploration of adherence to and divergence from trial criteria.

BACKGROUND: The role of GPs in recruiting or excluding participants critically underpins the feasibility, external validity and generalizability of primary care research. A better understanding of this role is needed. AIM: To investigate why GPs excluded potentially eligible participants from a large scale randomized controlled trial (RCT), to determine the proportion of patients excluded on account of trial eligibility compared with other reasons, and to explore the impact of such exclusions on the management and generalizability of RCTs. DESIGN AND SETTING: Secondary analysis of data from the CoBalT study, a multi-centre general-practice-based RCT investigating cognitive behavioural therapy as an adjunct to pharmacotherapy for treatment-resistant depression. METHOD: GPs were asked to screen patient lists generated from computerized record searches for trial eligibility and to provide narrative reasons for excluding patients. These reasons were coded independently by two researchers, with a third researcher resolving discrepancies. RESULTS: Thirty-one percent (4750/15,379) of patients were excluded at the GP screening stage, including 663 on patient lists that remained unscreened. Of the 4087 actively excluded patients, 67% were excluded on account of trial exclusion criteria, 20% for other criteria (half of which were comorbid conditions) and 13% without reason. CONCLUSION: Clear, comprehensive criteria, particularly with regards to comorbidities, are required for GPs to confidently screen patients for potential participation in research. Future studies should promote inclusivity and encourage GPs to adopt a liberal approach when screening patient lists. This would enhance the validity and generalizability of primary care research and encourage greater patient autonomy.

Cost-effectiveness of cognitive-behavioural therapy as an adjunct to pharmacotherapy for treatment-resistant depression in primary care: economic evaluation of the CoBalT Trial.

BACKGROUND: Depression is expensive to treat, but providing ineffective treatment is more expensive. Such is the case for many patients who do not respond to antidepressant medication. AIMS: To assess the cost-effectiveness of cognitive-behavioural therapy (CBT) plus usual care for primary care patients with treatment-resistant depression compared with usual care alone. METHOD: Economic evaluation at 12 months alongside a randomised controlled trial. Cost-effectiveness assessed using a cost-consequences framework comparing cost to the health and social care provider, patients and society, with a range of outcomes. Cost-utility analysis comparing health and social care costs with quality-adjusted life-years (QALYs). RESULTS: The mean cost of CBT per participant was £910. The difference in QALY gain between the groups was 0.057, equivalent to 21 days a year of good health. The incremental cost-effectiveness ratio was £14 911 (representing a 74% probability of the intervention being cost-effective at the National Institute of Health and Care Excellence threshold of £20 000 per QALY). Loss of earnings and productivity costs were substantial but there was no evidence of a difference between intervention and control groups. CONCLUSIONS: The addition of CBT to usual care is cost-effective in patients who have not responded to antidepressants. Primary care physicians should therefore be encouraged to refer such individuals for CBT.

Cognitive behavioural therapy as an adjunct to pharmacotherapy for primary care based patients with treatment resistant depression: results of the CoBalT randomised controlled trial.

BACKGROUND: Only a third of patients with depression respond fully to antidepressant medication but little evidence exists regarding the best next-step treatment for those whose symptoms are treatment resistant. The CoBalT trial aimed to examine the effectiveness of cognitive behavioural therapy (CBT) as an adjunct to usual care (including pharmacotherapy) for primary care patients with treatment resistant depression compared with usual care alone. METHODS: This two parallel-group multicentre randomised controlled trial recruited 469 patients aged 18-75 years with treatment resistant depression (on antidepressants for ≥6 weeks, Beck depression inventory [BDI] score ≥14 and international classification of diseases [ICD]-10 criteria for depression) from 73 UK general practices. Participants were randomised, with a computer generated code (stratified by centre and minimised according to baseline BDI score, whether the general practice had a counsellor, previous treatment with antidepressants, and duration of present episode of depression) to one of two groups: usual care or CBT in addition to usual care, and were followed up for 12 months. Because of the nature of the intervention it was not possible to mask participants, general practitioners, CBT therapists, or researchers to the treatment allocation. Analyses were by intention to treat. The primary outcome was response, defined as at least 50% reduction in depressive symptoms (BDI score) at 6 months compared with baseline. This trial is registered, ISRCTN38231611. FINDINGS: Between Nov 4, 2008, and Sept 30, 2010, we assigned 235 patients to usual care, and 234 to CBT plus usual care. 422 participants (90%) were followed up at 6 months and 396 (84%) at 12 months, finishing on Oct 31, 2011. 95 participants (46%) in the intervention group met criteria for response at 6 months compared with 46 (22%) in the usual care group (odds ratio 3·26, 95% CI 2·10-5·06, p<0·001). INTERPRETATION: Before this study, no evidence from large-scale randomised controlled trials was available for the effectiveness of augmentation of antidepressant medication with CBT as a next-step for patients whose depression has not responded to pharmacotherapy. Our study has provided robust evidence that CBT as an adjunct to usual care that includes antidepressants is an effective treatment, reducing depressive symptoms in this population. FUNDING: National Institute for Health Research Health Technology Assessment.

Psychological interventions for difficult-to-treat depression.

Mindfulness-based cognitive therapy (MBCT) may be helpful in preventing relapse in those with three or more depressive episodes. Recent research suggests it may also benefit those who have experienced fewer previous episodes of depression. If confirmed, this raises challenges of how MBCT is offered, accessed and supported.

Cognitive behavioural therapy as an adjunct to pharmacotherapy for treatment resistant depression in primary care: the CoBalT randomised controlled trial protocol.

BACKGROUND: Antidepressants are often the first-line treatment for depression but only one third of patients respond fully to pharmacotherapy. This paper describes the protocol for a randomised controlled trial (RCT) designed to evaluate the clinical and cost effectiveness of cognitive behavioural therapy (CBT) as an adjunct to pharmacotherapy for patients with treatment resistant depression in primary care. METHODS/DESIGN: CoBalT is a two parallel group multi-centre pragmatic RCT. Eligible participants were those who: (i) were aged 18-75years; (ii) were currently taking antidepressant medication (for at least 6weeks at an adequate dose); (iii) scored ≥14 on the Beck Depression Inventory (BDI-II); (iv) had adhered to their medication; and (v) met ICD-10 criteria for depression (assessed using the Clinical Interview Schedule - revised version). Those who gave written informed consent were randomised to one of two treatment groups: usual care or usual care plus CBT. The primary outcome is depressive symptoms assessed using the BDI-II at 6months post-randomisation. Secondary outcomes measured at 6 and 12months include quality of life, antidepressant use and health care utilisation. Outcomes will be analysed on an intention-to-treat basis. DISCUSSION: The CoBalT trial will provide evidence on the clinical and cost effectiveness of CBT as an adjunct to antidepressant medication in the treatment of depression that has not responded to pharmacotherapy. Given the move to widen access to 'talking therapies', the results of this study will be timely.

Cognitive behavioural therapy self-help for depression: an overview.

BACKGROUND: The World Health Organisation suggests that 60-80% of those affected by depression can be effectively treated using medication or psychotherapy within primary care. However, less than 50% of those affected actually receive such treatments. In practice, it remains a challenge to provide access to psychotherapy due to limited numbers of therapists combined with a growing number of treatment guidelines recommending the delivery of evidence-based psychological therapies such as cognitive behavioural therapy (CBT). One way to overcome this problem is to offer therapy in different ways - with so-called low-intensity (LI) working. One example of LI working is CBT self-help (CBT-SH). AIMS: To provide an overview of the current literature surrounding the effectiveness of CBT-SH with a particular focus on depression and discuss the future directions for both research and policy implementation. CONCLUSIONS: It is clear that self-help has a place within a healthcare framework but more work is needed to clarify where and how it should be delivered. The paper concludes that there appears to be enough benefits and sufficient evidence to argue for the introduction of LI working as an appropriate first step for most people facing depression and anxiety.

Compulsive hoarding: an interpretative phenomenological analysis.

BACKGROUND: This project aimed to explore the experiences of people who compulsively hoard and how they make sense of their own hoarding behaviours. METHOD: A total of 11 compulsive hoarders were recruited and interviewed using a simple semi-structured interview format, designed for the purposes of the study. The resulting transcribed interviews were analyzed using interpretive-phenomenological analysis. RESULTS: Four super-ordinate discrete, but interacting, themes were found: (1) childhood factors; (2) the participants' relationship to their hoarded items; (3) cognitive and behavioural avoidance of discard; and (4) the impact of hoarding on self, others and the home environment. The themes as a whole described people entrapped in massively cluttered physical environments of their own making. Efforts at discard appeared consistently sabotaged by cognitive/behavioural avoidance, thereby creating maintaining factors of associated personal distress and environmental decline. CONCLUSIONS: The results are discussed in the context of the extant evidence concerning hoarding, the distinct contribution made by the current results and the identified methodological shortcomings of the research approach.