Showing posts with label EBM. Show all posts
Showing posts with label EBM. Show all posts

7 April 2016

PSYCHOTHERAPY: TOO EXPENSIVE NOT TO PROVIDE




SUSAN MCNAIR MD, FRCPC

I have a patient in my practice that I have being seeing weekly for several months.  Together we work through problems he has had in the past week, with coworkers or family members or with his mood.  He is increasingly capable of seeing how these small weekly miseries relate to the abuse and neglect he endured as a child. 

 My job is to listen intently, and to shine light more directly on the pain of this – a yawning chasm that, for years, he saw as unrelated to his present difficulties.   I bill OHIP, the Ontario Health Insurance Plan, for each hour that he spends in my office.  


When he first presented, he indicated that he had seen several physicians for anxiety and depression-related complaints, as well as vague and undiagnosed physical problems which had each been thoroughly investigated with blood tests and x-rays.  He had daily suicidal ideation of varying intensity.  He had had 2 month-long hospital stays, tried 5 different antidepressant medications with variable effects and side effects, and had also had 2 courses of 12 sessions of cognitive-behavioural therapy which had been the most helpful interventions to date.  

 However, he still missed an average of one day a week of work, underachieved while at work due to anxiety, and had been on short-term disability 3 times in the past 5 years.  Sometimes, to his embarrassment, his wife would also miss work to stay home with him, worried by how unsafe and unwell he seemed.  “Defective”, he said, best captured how he felt about himself.  He was planning to apply for a disability support pension, despite his high degree of educational attainment.


This patient (an example based on several patients I see) well demonstrates the high cost of mental illness.  The economic impact of illness involves direct, indirect and human costs.  Direct costs are those incurred to treat the illness and rehabilitate the patient.  In this patient’s case, the cost of psychotherapy sessions are direct costs, as are his 2 previous hospitalizations, prescription medications, investigations for physical symptoms, and previous psychotherapy.  Many studies would also include his income support from short term disability and the disability support pension as direct costs.  


In 2011 in Canada  direct costs of mental health care were estimated at $42.3 billion (1).  Outpatient appointments for interventions such as psychotherapy account for only 8.5% of this total figure. Community services (27%) and income support (22.9%) dominate, with inpatient hospital care (16%) and prescription medication spending (15%) close behind (1).


Indirect costs, by contrast, refer to the various losses sustained in productivity due to illness.  In this patient’s case, for instance, his missed work days, decreased productivity while at work, and his withdrawal from the labour market would all be reflected as indirect costs of mental illness.  In addition, his wife’s loss of productivity as his caregiver would be reflected here as well.  These costs are clearly more difficult to measure, but one established method is to estimate the hours of work participation lost and multiply this by hourly wages.  Using this method, a 2012 study estimated that the Canadian economy may be losing almost $21 billion each year from lost productivity due to mental illness (2); an earlier 2006 study estimated lost caregiver productivity separately at almost $4 billion (3). 

These are the figures that spell “emergency” most clearly to governments, as each productivity loss spells lower tax revenue and consequences for public finances.


Finally, human costs: the pain, distress and loss of enjoyment of life incurred by mental illness, which are at once the most difficult to estimate and the most clinically pressing.  In economic terms, using a measure of disability-adjusted life years, this cost was estimated at $20.3 billion dollars in 2006 (3).  In human terms, this means a tide of misery not expressible as a dollar figure.  This is a mental health emergency for clinicians and, of course, for patients.


Professor Lord Richard Layard, a renowned economics professor and founder of the London School of Economics’ Centre for Economic Performance, spent most of his career tackling economic and GDP-impacting social issues in the UK such as unemployment and poverty.  But in more recent years he has turned his attention to the problem of mental illness.  He used his influence in academics and government to call for improved access to psychological therapies covered by that country’s National Health Service, under the aptly named “Improving Access to Psychological Therapies (IAPT)” initiative.  His argument for this was accepted as sound economics: according to the calculations of the Centre for Economic Performance, a one-time expenditure of on average £750 for a course of psychotherapy (10 sessions of CBT at £75 a session) resulted in cost savings of £750 per month in decreased direct costs and recouped indirect costs.  If government-funded psychotherapy resulted in just one month of improved function, he reasoned, this approach pays for itself (4).


Over the years since its initial rollout the IAPT has shown itself to be a cost-effective programme, although session costs were higher than expected (5) and functional recovery rates in the demonstration sites have been between 50 and 55%, with 5% returning to full employment from receiving sick benefits (6).  Remarkably the programme is described as cost-effective despite the fact that a full 55% of the patients referred did not in fact complete a course of treatment – they did not attend an initial appointment, declined after 1 or 2 sessions, or dropped out (5).  Perhaps this high drop-out rate is because the therapeutic alliance was not established early, or perhaps because CBT did not seem to address their problems. 

 As a national funding body the NHS has a responsibility to limit its funding to evidence-based treatments, and for decades CBT has led the way in the number and quality of available studies.  However, in fact the policy nowhere indicates that this approach should be limited to CBT.  Rather, the message is that effective psychotherapeutic treatments are economically sound additions to a publicly-funded healthcare system.  Results offset spending. 


Several months later, my patient still deals with anxiety and low mood.  But he can’t recall the last time he missed a day of work because of it.  His suicidal ideation is an occasional fleeting thought rather than a persistent daily grind.  He has days when he enjoys himself and the life he has built. He is being groomed for a promotion at work  and is now confident in promoting his ideas.  The thought of a disability pension is far from his mind.  His wife has also changed jobs –something she had not felt comfortable doing before.  We are gradually, but definitively, preparing for his discharge.

Has this therapy been expensive for the province to provide? 

Certainly it would have been prohibitive for the patient to afford out-of-pocket.  But what savings have been made by 1) avoided hospital stays 2) an avoided disability pension 3) vastly decreased missed work days 4) more work productivity 5) increased caregiver productivity and income 6) decreased visits and investigations for physical symptoms related to anxiety and depression 7) decreased use of resources not ultimately helpful to him (ie. further CBT) 8) a promotion in keeping with his training and skills?   

And what are the reduction in human costs and the improvement in quality of life worth?  It has been argued that it is not economical for psychiatrists to provide longer-term psychotherapy, but until there is an effective publicly-funded psychotherapy strategy in Ontario, I will continue – it is too expensive not to provide.


Notes *The patient example provided is based on representative data from a psychotherapy clinic and do not identify any one patient.


References:
1 1.   Smetanin P et al., The Life and Economic Impact of Major Mental Illnesses in Canada, RiskAnalytica, Report commissioned by the Mental Health Commission of Canada, December 2011.
2 2.   Conference Board of Canada, Mental Health Issues in the Labour Force: Reducing the Economic Impact on Canada, July 2012.
3 3.   Lim K-L  et al., How Much Should We Spend on Mental Health?,  Institute of Health Economics, Alberta, September 2008.
4 4.   The Centre for Economic Performance: Mental Health Group., The Depression Report: A New Deal for Depression and Anxiety Disorders, London School of Economics and Political Science, 2006.
5 5.  Radhakrishnan, M., Cost of Improving Access to Psychological Therapies (IAPT) programme: An analysis of cost of session, treatment and recovery in selected Primary Care Trusts in the East of England region.  Behaviour Research and Therapy, 2013, 51(37-45).
6 6.   Clark, D., Improving access to psychological therapy: Initial evaluation of two UK demonstration sites. Behaviour Research and Therapy, 2009, 47(11), 910-920.

23 March 2016

PUBLICATION BIAS UNDERMINES EVIDENCE BASED MEDICINE



                                     Mark Bennett MD, FRCPC 


The bias towards publishing positive results in research is well known, yet despite this nearly half of all clinical trial data goes unpublished.  The consequences are severe; biasing clinicians, harming patients, and affecting health care costs.

Without access to all clinical trial data harmful effects of treatments can go undetected. Examples of this include the COX-2 inhibitors and the diabetes drug rosiglitazone.  In the case of rofecoxib cases of myocardial infarction and causes of death were missing from clinical trial reports, and the association between the drug and heart attacks was undetected, until the drug was eventually pulled from market1.   

Meta-analysis that included unpublished data examining the cardiac effects of celecoxib also found an association with myocardial infarction2. In 2004, a legal settlement required the makers of rosiglitazone to make available all clinical trial results. A meta-analysis with access to this data, showed a significant association with the drug to MI
and cardiovascular death3. 
 

Publication bias misleads clinicians and ultimately their patients by inflating effect size estimates of the treatments they provide. This effects the risk-benefit discussion clinicians have with their patients.   

Turner et al.4 demonstrated this in a meta-analysis that accessed all phase 2 and 3 trials for 12 antidepressant agents approved by the FDA between 1987-2004, accessed through Freedom of Information Act requests.  Of these 74 trials, 38 were deemed by the FDA to support the efficacy of the drug.  Of those 37 were published in academic journals.  The remaining 36 trials were deemed negative or questionable by the FDA. Of those 22 were unpublished while the others were published as positive conflicting with the FDA’s assessment.  When effect size estimates from these trials do not include unpublished trial data, they are overestimated4.  One might think that trials were unpublished due to methodological flaws, however unpublished trials were not found to differ significantly in terms of sample size or methodology.  Systematic review and meta-analysis were revolutionary in terms of their impact on modern medicine, and they are undermined by publication bias4. 


Perhaps the example of publication bias that has gathered the most media attention is that of the anti-viral oseltamivir. Billions of dollars of the drug have been stockpiled by governments across the globe in preparation for influenza outbreaks, generating approximately 18 billions dollars in sales for its maker.  These decisions were made without approximately 60% of the clinical trial data.  

However following a five-year campaign by Cochrane reviewers and the British Medical Journal, the full data set was made available, and the revised meta-analysis suggested the small benefits provided by Tamiflu do not outweight the harms5.

Why does publication bias occur?  It’s commonly believed that medical journals are more likely to publish clinical trials if they are positive.  However the largest systematic review of studies investigating publication bias did not find this to be the case6.  In a pooled analysis of four prospective studies following clinical trials submitted for publication, the direction of the results did not predict publication6. 

 Inception cohort studies however, where trials are followed to publication from their design, found that trials were approximately three times more likely to be published if positive.  This suggests that it is the investigator’s decision to publish, more so than editorial decisions, that leads to publication bias6. 

When authors are surveyed regarding their reasons for not submitting articles for publication, most common reasons include, lack of time or low priority, results not seeming important enough, and fear of journal rejection. Finally industry sponsorship has been repeatedly associated with publication bias, with positive industry trial found be three to four times more likely to be published if positive6. 

Not only are the consequences of publication bias severe, methods in detection, such as funnel plots, are often ineffective7.  Efforts in prevention have focused primarily on clinical trial registries.  Clinicaltrials.gov and similar online clinical trial registries in Europe were created in the early 2000’s. In 2005 the International Committee of Medical Journal Editors (ICMJE) required, in a nonbinding agreement, that all clinical trials should be indexed in a clinical trial registry to qualify for publication in a journal.  

Perhaps, the legislation with the most potential for increasing access to clinical trial data was the FDA Amendment Act (2008).  This legislation required that all clinical trial results be disseminated on clinicaltrials.gov within one year of the studies completion.   However Gopal et al8 evaluated the rate of compliance with the act and found only 19.1% of trials had available results in 2007-8 and 10.8% in 2008-9.  A more recent systematic review of interventions against publication bias demonstrated that although the use of prospective trial registration has been increasing, the over representation of positive results in the published literature persists9.  

Within psychiatry, Scott et al.10 reviewed the registry information of all published clinical trials in five journals adhering to the ICMJE agreement, including The American Journal of Psychiatry, Archives of General Psychiatry/JAMA Psychiatry, Biological Psychiatry, The Journal of Child and Adolescent Psychiatry, and the Journal of Clinical Psychiatry; 181 trials in total.  It was found that only 15% of trials were registered prospectively, without any changes to their primary outcome measure. 

Advances in evidence-based medicine, such as systematic review and meta-analysis have shaped clinical practice in dramatic ways.  With new technologies and decision making tools evidence is more accessible to clinicians to inform their patients better.  These tools however rely on access to all the clinical trial data to truly be effective; otherwise they may be leading physicians and their patients astray.

Public awareness of the impact of publication bias is increasing, much in thanks to the work of the AllTrials campaign11, an international organization founded by psychiatrist and epidemiologist Dr. Ben Goldacre, which calls for all clinical trials in humans to be registered and results be reported. Systems are in place to achieve this but monitoring and enforcement are lacking.  There is an urgency to implement these measures to improve the health and safety of our patients. 

References

11.  Topol EJ. Failing the Public Health — Rofecoxib, Merck, and the FDA. N Engl J Med 2004; 351:1707-170.
2 2. Caldwell B, Aldington, S, Weatherall M, Shirtcliff, P, Beassley R. J R Soc Med 2006, 99: 132-140
33.   Nissen SE, Wolski K. N Engl J Med 2007, 356:2457-2471
44.   Turner EH, Matthews AM, Linardatos E, Tell RA, Rosenthal.  N Engl J Med 2008; 358(3):252-60.
55.   Jefferson T, Jones M, Doshi P, Spencer EA, Onakpoya I, Heneghan CJ BMJ 2014;348:g2545.
66.   Song F, Parekh S, Hooper L, Loke YK, Ryder J, Sutton AJ, Hing C, Kwok CS, Pang C, Harvey I. Dissemination and publication or research finding: an updated related biases. Health Technology Assessment 10 (9); 2010.
77.   Terrin N, Schmid CH, Lau J. In an empirical evaluation of the funnel plot, researchers could not visually identify publication bias. J Clin Epidemiol 2005.
88.  Gopal RK, Yamashita TE, Prochazka AV. Research without results: Inadequate public reporting of clinical trial results. Contemp Clin Trials 2012; 33 (3):486-491. 
99.   Thaler K, Kien C, Nussbaumer B, Van Noord MG, Griebler U, Klerings I, Gartlehner G. Inadequate use and regulation of interventions against publication bias decreases their effectiveness: a systematic review. J Clin Epidemiol 2015; 68(7):792-802.
110. Scott A, Rucklidge J, Mulder R.  Is Mandatory Prospective Trial Registration Working to Prevent Publication of Unregistered Trials and Selective Outcome Reporting? An Observational Study of Five Psychiatry Journals That Mandate Prospective Clinical Trial Registration. PloS One 2015:e0133718.
111. alltrials.net