See original letter by Amos.
Dr McGorry and Colleagues Reply
To the Editor: Dr Amos, a local colleague, makes the fairly obvious intellectual point that the design of our study1 is unable to definitively prove that the young people who were randomized to 3 active treatment conditions and who improved over the course of the trial would not have had the same outcomes if treatment had been withheld. However, we believe, for 2 reasons, that our interpretation is correct that even relatively nonspecific, yet comprehensive, psychosocial intervention is very likely to have helped these patients to improve.
Firstly, the baseline characteristics of the sample2 indicate that these help-seeking patients are experiencing severe distress, a range of comorbid syndromes, moderately severe functional impairment, and substantial risk of self-harm. It is most unlikely that they would, as a group, have recovered naturalistically, and indeed it would have been unethical in our view to withhold or delay treatment, as Dr Amos seems to have implied we should have done. Real-world clinical research cannot always manage the methodological purity that armchair critics demand. However, provided safety and informed consent can be assured, one potential solution may be to conduct future studies of this kind using a "stepped wedge" cluster randomized trial design,3 which allows all participants to receive effective care, but through randomized delay in commencement there is some capacity to safely study the effect of no intervention. Secondly, our long-term follow up data on the ultra-high risk cohort4,5 show that this clinical phenotype is persistent and disabling and that natural remissions are the exception rather than to be expected.
Finally, it is puzzling that Dr Amos goes beyond methodology to accuse us of spin and bias. We have expressed, in good faith, in a peer-reviewed article our interpretation of the data, reinforced by our 20-year clinical experience with this patient group. These young patients and their families seek and benefit from the evidence-informed clinical care we provide, and, together with international research colleagues, we aim in the future to increase our knowledge base about what works.
1. McGorry PD, Nelson B, Phillips LJ, et al. Randomized controlled trial of interventions for young people at ultra-high risk of psychosis: twelve-month outcome. J Clin Psychiatry. 2013;74(4):349-356. PubMed doi:10.4088/JCP.12m07785
2. Phillips LJ, Nelson B, Yuen HP, et al. Randomized controlled trial of interventions for young people at ultra-high risk of psychosis: study design and baseline characteristics. Aust N Z J Psychiatry. 2009;43(9):818-829. PubMed doi:10.1080/00048670903107625
5. Nelson B, Yuen H-P, Wood SJ, et al. Long-term follow-up of a group at ultra-high risk ("prodromal") for psychosis: the PACE 400 study [published online ahead of print June 5, 2012]. Arch Gen Psychiatry. doi:10.1001/jamapsychiatry.2013.1270 PubMed
Author affiliations: Orygen Youth Health Research Centre, Centre for Youth Mental Health, Department of Psychiatry, University of Melbourne, Parkville, Australia (Drs McGorry, Nelson, and Amminger); Institute of Brain, Behaviour and Mental Health, University of Manchester, Manchester, England (Dr Yung); and Melbourne School of Psychological Sciences, University of Melbourne, Melbourne, Australia (Dr Phillips).
Potential conflicts of interest: Dr McGorry has served as a consultant to AstraZeneca, Eli Lilly, Janssen-Cliag, Pfizer, and Bristol-Myers Squibb; has received grant/research support from the Colonial Foundation and the National Health and Medical Research Council of Australia (NHMRC); and has received honoraria from AstraZeneca, Eli Lilly, Janssen-Cilag, Pfizer, and Bristol-Myers Squibb. Dr Yung has received grant/research support from Janssen-Cilag, the Colonial Foundation, and NHMRC and has received travel support from Janssen and Bristol-Myers Squibb. Dr Phillips has received grant/research support from Janssen-Cilag, the Colonial Foundation, and NHMRC. Drs Nelson and Amminger report no potential conflicts of interest relevant to the subject of this letter..
Funding/support: The study discussed in this letter was supported by an investigator-initiated research grant from Janssen-Cilag.
J Clin Psychiatry 2013;74(11):1123 (doi:10.4088/JCP.13lr08602a).
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