Journal of Child Psychology and Psychiatry 55:11 (2014), pp 1185–1186
doi:10.1111/jcpp.12343
Editorial: Trials and tribulations in child psychology and psychiatry: what is needed for evidence-based practice If your child had leukaemia you would be distraught. Yet, there would also be hope. Most children with a diagnosis of leukaemia start their treatment as part of ongoing trials. The clinical teams looking after such children are motivated, knowledgeable and work in centres that specialise in the treatment of this lethal illness. There are clear step-by-step protocols to treat these children, specialist nurses ensure that they are adhered to, doctors have been trained to deal swiftly with the side effects of the treatments, symptoms and laboratory parameters are measured carefully and used to guide treatment. The results speak for themselves. Not only have the trials helped oncologists learn more about which treatments work best, but for years we have known that those who enter trials do better than those patients with similar characteristics who don’t. We have recently also learnt that trials improve survival rates in those cancers population wide: the annual reduction between 1978-2005 in risk of death from childhood cancers ranged from 2.7% to 12.0% (Stiller, Kroll, & Pritchard-Jones, 2012). This cancer trial culture is a splendid example of British health care delivery. What is happening in child psychiatry though? If your child had, say, depression you would have every reason to be distraught too. The mortality rate is higher than in the general population and the burden of disease in the long run heavier than that of cardiovascular illness or cancer (Collins et al., 2011). Yet, your child would not have access to a trial. Instead, you would probably struggle to have your child’s depression recognised in the first place. The care you would get would be determined by extreme regional variations and by what resources are available to local services and often the ideology or preferences of practitioners. From a survey my colleagues and I are working on, we know that measurement of outcome is the great exception for children treated in child psychiatric clinics, as is the measurement of children’s side effects. Instead, treatment decisions are often made on clinical impression, and knee-jerk reactions (such as premature stopping of drug treatment) seem common. Anecdotal evidence further suggests that antidepressants and antipsychotics are often used for challenging patients, for instance those who are aggressive or suicidal, rather than those who we know from the evidence might benefit from them. Even worse, the evidence-based options for depression (let alone other child-psychiatric illnesses) are too few as a result of too few trials. In a shameful contrast to the cancer field, the UK has produced very little for the treatment of depression in youth, with a few notable exceptions (Goodyer et al., 2007). Would you accept your child with depression being treated as a lesser human being than your child with cancer? It seems like we do, and this of course is a tragedy.
Several factors may explain this state of affairs. Our relative lack of knowledge of pathophysiology is only part of the reason. Lots of trials in cancer research are of the type: is the AB sequence of treatment better than the BA sequence? There is plenty such work to be done in child psychiatry: should you start with an antidepressant or with CBT, would a parenting intervention help in select cases as an augmentation, does quetiapine augmentation work in adolescents as well as it works in adults? Such simple questions begging for . . . there is every an answer are plenty in reason to be hopeful most areas in our field, that many of our basic not just depression. It clinical questions in goes beyond the scope child psychiatry would of this Editorial to be resolved by good describe the difficulties trials. Rather than ‘go with recruiting patients calculate’ our charge from psychiatric clinics. Obviously, part of the should be ‘go do more problem has to do with trials’, and we should the scandalously unfair make it resonate like a investment in the pub- battle cry lic’s mental health compared to cancer medicine. Yet, while oncologists see it as their duty to have their patient enter a trial, we often seem to be doing our utmost to ensure that a patient doesn’t even fill in a research questionnaire. Resources alone cannot account for such a difference in ethos. Strong emotional reactions towards medication for psychiatric illness in youth may be responsible for the dearth of drug trials in this country, but cannot explain that even psychological treatment trials are hard to come by. An obvious reason is the lack of funding to do trials. I heard with envy that two charities (Leukaemia Lymphoma Research and the Kay Kendall Leukaemia Fund) have as their declared goal to help run trials in cancer units. Wouldn’t it be wonderful if the children with mental illness in our society had similar benefactors? Finally, what do researchers and those involved in research dissemination do about trials? It is easy to be put off doing trials. Regulation raises her ugly (even if sometimes necessary) head in each and every step of planning anything trial-like, and one has to wait for quite a long time to reap the benefits of doing trial research. Moreover, many researchers see trials as a bit of a gamble—a treatment that works is a game- (and career-) changer; however, a trial with negative results is typically not seen fit for the big journals. This is a major disincentive in today’s university funding climate. This Journal has been at the forefront of publishing high-quality trials (Maughan, 2013). Most to date have been psychological therapies, though JCPP has
© 2014 Association for Child and Adolescent Mental Health. Published by John Wiley & Sons Ltd, 9600 Garsington Road, Oxford OX4 2DQ, UK and 350 Main St, Malden, MA 02148, USA
1186
Editorial
recently had some fine pharmacological research in the field. Importantly, this Journal is seeing the great importance in informing practitioners and the public not only of the glorious successes of treatment trials, but also of the failures of well-conducted studies. One prime example is the randomised controlled trial (RCT) on dyslexia by Duff et al.1 in this issue. We don’t know much about how to improve reading and language skills in children who are at risk for dyslexia. The trial by Duff et al. conceptualised being at risk in a novel way, that is, by combining familial risk and/or the presence of preschool language impairments. It was also conducted with a population of 6-year olds and delivered alongside formal literacy instruction, unlike previous trials. The intervention had both a reading and language strand delivered in a group and individual setting. The authors found that those in the treatment group were doing slightly better than those in the wait list control on letter knowledge, phoneme awareness and taught vocabulary. However, there were no reliable differences between groups for the primary outcome of word-level reading. As the authors note, the negative result is disappointing, yet important for education purposes and for raising the standards of trial reporting. I would add that reporting negative results can be particularly informative when the reasons for the null results are carefully thought about—as is done in the Duff et al. article. We often learn from our failed attempts and such creative failures confer crucial knowledge. The Practitioner Review by Panter-Brick and colleagues is yet another example of learning from what hasn’t been done or done wrongly to improve future practice. The authors evaluate the extent to which fathers have been included in research studies, intervention trials and policy approaches and find that – as expected – there are several biases operating against the inclusion of fathers in studies. They argue that not engaging fathers could have an adverse impact on interventions. As Ramchandani and Iles point out in their commentary, the evidence suggests that in most cases engaging fathers can be helpful, but there are simple practical obstacles such as working hours. From a researcher’s point of view it would also be interesting to evaluate gender differences in the aptitude (and willingness) to engage in socially complex situations such as dealing with mental health services or research studies. Men who have attended their wives antenatal class know that in such considerations may be found further clues about the obstacles in recruiting fathers. The importance of family-based interventions becomes apparent even for conditions that are not typically seen by child psychiatrists in the first place. In yet another randomised controlled trial published in this issue of JCPP, Wallander and colleagues provide evidence for the beneficial effects of Early Developmental Intervention in children at risk for developing adverse outcomes (for example, through
perinatal asphyxia). An important aspect is that this research was conducted in low and middle-income countries (LMIC) where most of the world’s children live. The study included families from Pakistan, Zambia and India. Interestingly, the intervention worked best for cognitive abilities at 36 months but were not statistically significant for general development as rated by parents. The fact that this RCT appeared to work across risk exposures suggests that it may be a useful way of tackling the effects of a relatively broad set of adversities worldwide. Leibniz, the mathematician and philosopher, thought that much dispute and therefore decision making would one day be resolved through calculation—he argued that when searching for answers to complex questions we would charge one another ‘go calculate’. The great German’s optimism has so far proven unfounded. Yet, there is every reason to be hopeful that many of our basic clinical questions in child psychiatry would be resolved by good trials. Rather than ‘go calculate’, our charge should be ‘go do more trials’, and we should make it resonate like a battle cry.
Argyris Stringaris Joint Editor Acknowledgements A.S has declared potential conflicts of interest in his role as joint Editor of JCPP, as indicated below. He has declared that there are no competing or potential conflicts of interest in relation to this Editorial. A.S: Grants awarded from Wellcome Trust, the National Institute for Health Research (NIHR) and the Department of Health, UK. Royalties from Cambridge University Press for his book The Maudsley Reader in Phenomenological Psychiatry. Serves on the Editorial Board of the Journal of the American Academy of Child and Adolescent Psychiatry.
Note 1. Articles that are in this issue (with italicized names on first mention) can be found at: http:// onlinelibrary.wiley.com/doi/10.1111/jcpp.2014. 55.issue-11/issuetoc.
References Collins, P.Y., Patel, V., Joestl, S.S., March, D., Insel, T.R., & Daar, A.S., . . . & Stein, D.J. (2011). Grand challenges in global mental health. Nature, 475, 27–30. Goodyer, I., Dubicka, B., Wilkinson, P., Kelvin, R., Roberts, C., Byford, S., .. & Harrington, R. (2007). Selective serotonin reuptake inhibitors (SSRIs) and routine specialist care with and without cognitive behaviour therapy in adolescents with major depression: randomised controlled trial. British Medical Journal, 335, 142. Maughan, B. (2013). Editorial: “Better by design” – why randomized controlled trials are the building blocks of evidence-based practice. Journal of Child Psychology and Psychiatry, 54, 225–226. Stiller, C.A., Kroll, M.E., & Pritchard-Jones, K. (2012). Population survival from childhood cancer in Britain during 1978-2005 by eras of entry to clinical trials. Annals of Oncology, 23, 2464–2469. © 2014 Association for Child and Adolescent Mental Health.
doi:10.1111/jcpp.12343
Editorial: Trials and tribulations in child psychology and psychiatry: what is needed for evidence-based practice If your child had leukaemia you would be distraught. Yet, there would also be hope. Most children with a diagnosis of leukaemia start their treatment as part of ongoing trials. The clinical teams looking after such children are motivated, knowledgeable and work in centres that specialise in the treatment of this lethal illness. There are clear step-by-step protocols to treat these children, specialist nurses ensure that they are adhered to, doctors have been trained to deal swiftly with the side effects of the treatments, symptoms and laboratory parameters are measured carefully and used to guide treatment. The results speak for themselves. Not only have the trials helped oncologists learn more about which treatments work best, but for years we have known that those who enter trials do better than those patients with similar characteristics who don’t. We have recently also learnt that trials improve survival rates in those cancers population wide: the annual reduction between 1978-2005 in risk of death from childhood cancers ranged from 2.7% to 12.0% (Stiller, Kroll, & Pritchard-Jones, 2012). This cancer trial culture is a splendid example of British health care delivery. What is happening in child psychiatry though? If your child had, say, depression you would have every reason to be distraught too. The mortality rate is higher than in the general population and the burden of disease in the long run heavier than that of cardiovascular illness or cancer (Collins et al., 2011). Yet, your child would not have access to a trial. Instead, you would probably struggle to have your child’s depression recognised in the first place. The care you would get would be determined by extreme regional variations and by what resources are available to local services and often the ideology or preferences of practitioners. From a survey my colleagues and I are working on, we know that measurement of outcome is the great exception for children treated in child psychiatric clinics, as is the measurement of children’s side effects. Instead, treatment decisions are often made on clinical impression, and knee-jerk reactions (such as premature stopping of drug treatment) seem common. Anecdotal evidence further suggests that antidepressants and antipsychotics are often used for challenging patients, for instance those who are aggressive or suicidal, rather than those who we know from the evidence might benefit from them. Even worse, the evidence-based options for depression (let alone other child-psychiatric illnesses) are too few as a result of too few trials. In a shameful contrast to the cancer field, the UK has produced very little for the treatment of depression in youth, with a few notable exceptions (Goodyer et al., 2007). Would you accept your child with depression being treated as a lesser human being than your child with cancer? It seems like we do, and this of course is a tragedy.
Several factors may explain this state of affairs. Our relative lack of knowledge of pathophysiology is only part of the reason. Lots of trials in cancer research are of the type: is the AB sequence of treatment better than the BA sequence? There is plenty such work to be done in child psychiatry: should you start with an antidepressant or with CBT, would a parenting intervention help in select cases as an augmentation, does quetiapine augmentation work in adolescents as well as it works in adults? Such simple questions begging for . . . there is every an answer are plenty in reason to be hopeful most areas in our field, that many of our basic not just depression. It clinical questions in goes beyond the scope child psychiatry would of this Editorial to be resolved by good describe the difficulties trials. Rather than ‘go with recruiting patients calculate’ our charge from psychiatric clinics. Obviously, part of the should be ‘go do more problem has to do with trials’, and we should the scandalously unfair make it resonate like a investment in the pub- battle cry lic’s mental health compared to cancer medicine. Yet, while oncologists see it as their duty to have their patient enter a trial, we often seem to be doing our utmost to ensure that a patient doesn’t even fill in a research questionnaire. Resources alone cannot account for such a difference in ethos. Strong emotional reactions towards medication for psychiatric illness in youth may be responsible for the dearth of drug trials in this country, but cannot explain that even psychological treatment trials are hard to come by. An obvious reason is the lack of funding to do trials. I heard with envy that two charities (Leukaemia Lymphoma Research and the Kay Kendall Leukaemia Fund) have as their declared goal to help run trials in cancer units. Wouldn’t it be wonderful if the children with mental illness in our society had similar benefactors? Finally, what do researchers and those involved in research dissemination do about trials? It is easy to be put off doing trials. Regulation raises her ugly (even if sometimes necessary) head in each and every step of planning anything trial-like, and one has to wait for quite a long time to reap the benefits of doing trial research. Moreover, many researchers see trials as a bit of a gamble—a treatment that works is a game- (and career-) changer; however, a trial with negative results is typically not seen fit for the big journals. This is a major disincentive in today’s university funding climate. This Journal has been at the forefront of publishing high-quality trials (Maughan, 2013). Most to date have been psychological therapies, though JCPP has
© 2014 Association for Child and Adolescent Mental Health. Published by John Wiley & Sons Ltd, 9600 Garsington Road, Oxford OX4 2DQ, UK and 350 Main St, Malden, MA 02148, USA
1186
Editorial
recently had some fine pharmacological research in the field. Importantly, this Journal is seeing the great importance in informing practitioners and the public not only of the glorious successes of treatment trials, but also of the failures of well-conducted studies. One prime example is the randomised controlled trial (RCT) on dyslexia by Duff et al.1 in this issue. We don’t know much about how to improve reading and language skills in children who are at risk for dyslexia. The trial by Duff et al. conceptualised being at risk in a novel way, that is, by combining familial risk and/or the presence of preschool language impairments. It was also conducted with a population of 6-year olds and delivered alongside formal literacy instruction, unlike previous trials. The intervention had both a reading and language strand delivered in a group and individual setting. The authors found that those in the treatment group were doing slightly better than those in the wait list control on letter knowledge, phoneme awareness and taught vocabulary. However, there were no reliable differences between groups for the primary outcome of word-level reading. As the authors note, the negative result is disappointing, yet important for education purposes and for raising the standards of trial reporting. I would add that reporting negative results can be particularly informative when the reasons for the null results are carefully thought about—as is done in the Duff et al. article. We often learn from our failed attempts and such creative failures confer crucial knowledge. The Practitioner Review by Panter-Brick and colleagues is yet another example of learning from what hasn’t been done or done wrongly to improve future practice. The authors evaluate the extent to which fathers have been included in research studies, intervention trials and policy approaches and find that – as expected – there are several biases operating against the inclusion of fathers in studies. They argue that not engaging fathers could have an adverse impact on interventions. As Ramchandani and Iles point out in their commentary, the evidence suggests that in most cases engaging fathers can be helpful, but there are simple practical obstacles such as working hours. From a researcher’s point of view it would also be interesting to evaluate gender differences in the aptitude (and willingness) to engage in socially complex situations such as dealing with mental health services or research studies. Men who have attended their wives antenatal class know that in such considerations may be found further clues about the obstacles in recruiting fathers. The importance of family-based interventions becomes apparent even for conditions that are not typically seen by child psychiatrists in the first place. In yet another randomised controlled trial published in this issue of JCPP, Wallander and colleagues provide evidence for the beneficial effects of Early Developmental Intervention in children at risk for developing adverse outcomes (for example, through
perinatal asphyxia). An important aspect is that this research was conducted in low and middle-income countries (LMIC) where most of the world’s children live. The study included families from Pakistan, Zambia and India. Interestingly, the intervention worked best for cognitive abilities at 36 months but were not statistically significant for general development as rated by parents. The fact that this RCT appeared to work across risk exposures suggests that it may be a useful way of tackling the effects of a relatively broad set of adversities worldwide. Leibniz, the mathematician and philosopher, thought that much dispute and therefore decision making would one day be resolved through calculation—he argued that when searching for answers to complex questions we would charge one another ‘go calculate’. The great German’s optimism has so far proven unfounded. Yet, there is every reason to be hopeful that many of our basic clinical questions in child psychiatry would be resolved by good trials. Rather than ‘go calculate’, our charge should be ‘go do more trials’, and we should make it resonate like a battle cry.
Argyris Stringaris Joint Editor Acknowledgements A.S has declared potential conflicts of interest in his role as joint Editor of JCPP, as indicated below. He has declared that there are no competing or potential conflicts of interest in relation to this Editorial. A.S: Grants awarded from Wellcome Trust, the National Institute for Health Research (NIHR) and the Department of Health, UK. Royalties from Cambridge University Press for his book The Maudsley Reader in Phenomenological Psychiatry. Serves on the Editorial Board of the Journal of the American Academy of Child and Adolescent Psychiatry.
Note 1. Articles that are in this issue (with italicized names on first mention) can be found at: http:// onlinelibrary.wiley.com/doi/10.1111/jcpp.2014. 55.issue-11/issuetoc.
References Collins, P.Y., Patel, V., Joestl, S.S., March, D., Insel, T.R., & Daar, A.S., . . . & Stein, D.J. (2011). Grand challenges in global mental health. Nature, 475, 27–30. Goodyer, I., Dubicka, B., Wilkinson, P., Kelvin, R., Roberts, C., Byford, S., .. & Harrington, R. (2007). Selective serotonin reuptake inhibitors (SSRIs) and routine specialist care with and without cognitive behaviour therapy in adolescents with major depression: randomised controlled trial. British Medical Journal, 335, 142. Maughan, B. (2013). Editorial: “Better by design” – why randomized controlled trials are the building blocks of evidence-based practice. Journal of Child Psychology and Psychiatry, 54, 225–226. Stiller, C.A., Kroll, M.E., & Pritchard-Jones, K. (2012). Population survival from childhood cancer in Britain during 1978-2005 by eras of entry to clinical trials. Annals of Oncology, 23, 2464–2469. © 2014 Association for Child and Adolescent Mental Health.
