A randomised controlled trial was planned to compare two different
treatment strategies — structured problem solving and selective
serotonin reuptake inhibitor (SSRI) medication — for patients with
mild to moderate major depression. The trial was to be conducted in the
primary care setting with all treatment given by general
practitioners. When no patients had been recruited into the study
after six months, we performed an audit of all patients with
depressive symptoms attending the doctors' practices over three
weeks. Exclusion criteria were changed to ease entry into the trial,
but still no patients were recruited over the following six months.
What went wrong?
MJA 2001; 174: 144-146
Why did the trial fail? -
More articles on General practice and primary care
The recent National Survey of Mental Health and Wellbeing found that
depression was associated with significant disability and that 6.3%
of the Australian population was estimated to have suffered a major
depressive disorder in the previous 12 months.1 The survey also
showed that general practices were the main points of contact for
patients with a mental disorder, consistent with previous reports
that only 5% of such patients are referred to
psychiatrists.2 As most depressed patients
will be treated in primary care, the evaluation of treatment in this
setting is important.
Structured problem solving is emerging as an effective treatment for
clinical depression.3-6 This treatment aims to
teach patients to use their own resources to deal with their problems
and includes skills such as identifying and simplifying problems,
"brainstorming" potential solutions, and implementing these
solutions. The treatment is brief, has clearly identified stages,
and is very suitable for delivery by primary healthcare
professionals. However, little research in primary care settings
has used general practitioners as the main treatment providers, and
thus the degree to which the evidence for the effectiveness of
structured problem solving can be generalised to general practice is
questionable. For this reason we designed a randomised trial with all
treatment conducted by GPs (Box 1). The study was, in part, a
replication of an earlier United Kingdom project that showed that
problem solving was better than placebo, but equivalent to
Six months after the trial commenced no patients
had been recruited.
In practical terms, the trial should not have failed, as mild to
moderate depression is a common presentation in primary care and the
research protocol addressed many of the problems identified in
previous primary care research failures.9,10 For example:
- We used GPs
who had participated in a Masters program designed to improve the
recognition and management of mental disorders in general practice;
- We involved the participating GPs in the development of the
- We made every effort to minimise tasks involved in the study for the
- The chief investigator was responsible for the teaching on the
Masters program, and had developed a close working relationship with
While our original intention was not to address the complexity of
conducting randomised trials in clinical practice, the apparent
unease of many of the GPs with randomisation raises some potential
reasons for the failure (Box 2). Apparent ambivalence towards
randomisation in medicine, despite strong support in the scientific
literature, has been reported previously.11 Silverman argues that as
medicine shifts from the traditional authoritarian stance of
"doctor knows best" towards the use of clinical guidelines and
standardised treatment protocols, there is an increased discomfort
in any approach that might be seen to admit a lack of crucial knowledge
on the part of the doctor.11 In other words, asking
patients to consent to randomisation between two conditions admits
an uncertainty that compromises the traditional doctor-patient
However, it has not been difficult to engage doctors in trials
involving randomisation of their patients, and there is evidence
that many are prepared to follow simple randomisation
protocols.12 For example, one of the
first randomised controlled trials of giving aspirin to patients
very early after myocardial infarction (to stop or reverse the
thrombotic process) enrolled 2500 GPs. These GPs, who were blind to
the treatment condition they were offering, agreed to give the
allocated capsules (aspirin or placebo) to any patient who presented
with chest pain or other symptoms likely to be caused by a myocardial
infarct. Two thousand patients were recruited into the trial,
suggesting that, in this example, randomisation was not a
substantial concern. If it is not randomisation per se that
causes reluctance to recruit, then other factors need
In our study, the audit results indicated that one in six patients had
been excluded because the GPs lacked confidence that structured
problem solving would be of benefit. Perhaps the GPs lacked
confidence in their ability to deliver the psychological treatment
effectively. If this is the case, the failure of this trial may have
been influenced by the inclusion of a psychological treatment. We
have argued elsewhere that doctors remain cautious about using
non-drug treatments, partly because of the lack of organised
promotion of non-proprietary treatments, and partly because of the
difficulty in ensuring quality control.13 Yet, these GPs had agreed
problem solving was a useful treatment, had demonstrated competence
as part of their training, and two GPs in the group had conducted their
own research projects where they taught structured problem solving
to other doctors.
It is also possible that, given the obvious differences between the
psychological and pharmacological approaches, the GPs had formed an
opinion early in the recruitment process that one or other approach
would better suit a particular patient. In this case, exclusion from
the trial was based on the presumption that the doctor already knew
what treatment was best.11,14 In a disturbing
example of "doctor knows best", two-thirds of suitable patients were
not enrolled in a randomised trial of antiarrhythmia drugs because
their doctors were so convinced of the benefits of the drugs that they
did not want their patients allocated to the placebo
group.15 The study eventually
showed that these drugs were capable of causing fatal arrhythmias, so
those doctors were essentially withholding from their patients the
50% chance of being allocated to the safer placebo alternative.
Other factors may cause doctors to hesitate when faced with
recruiting patients, including the complexities of obtaining
informed consent, the need to complete clinical ratings or ask
patients to complete self-report questionnaires for measurement of
outcome, or the need to work within a specific treatment protocol.
Although tasks for the GPs were minimal, it is likely that the
necessary role change from practitioner to scientist-practitioner
was too great to facilitate a shift in treating behaviour. If this is
the case, the inherent contradiction between research and delivery
of care in the minds of many clinicians is a basic problem for clinical
Nevertheless, treatments that are efficacious in research settings
need to be evaluated under the conditions of routine care, and it may
not be sufficient to rely on the use of qualitative methods to evaluate
outcome in primary care.17 Perhaps an explicit use of
the "uncertainty principle" in randomised controlled trials within
routine clinical care will enhance recruitment rates.18 That is, if
there is apparent certainty about what treatment is best, it is
ethically untenable that patients should have their treatment
chosen at random, so only patients for whom there is uncertainty about
which treatment would be best should be recruited into a randomised
trial. In this way the ethical dilemma for clinicians is solved, and
the heterogeneity of the patient sample maintained, as clinicians
will differ significantly in the types of patients they will be
uncertain about. Financial incentives might increase the
involvement of clinicians in research, but have caused public outcry
in the United States;19,20 the resulting
assertive recruiting can also erode informed consent.21,22
We argue instead that a more fundamental shift in ethos and knowledge
of principles that underlie research in clinical practice is
required. This argument has parallels in the recent Royal Australian
College of General Practitioners report on an implementation
strategy for evidence-based clinical practice
guidelines.23 The report points to a lack
of understanding of the principles underpinning the use of clinical
practice guidelines in general practice, and the need to develop a
culture in which such guidelines are used and valued. In regard to
outcome research, until doctors accept a scientist-practitioner
model of practice it is unlikely that they will feel comfortable using
conventional research protocols.
Clinical research conducted in routine care will help clinicians
make informed decisions about what may be the best treatment for their
patients based on scientifically derived knowledge. We hope that the
questions raised in this article will stimulate debate and research
that will directly address this important issue.
This research was supported by a grant from the School of Psychiatry,
University of New South Wales.
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Mynors-Wallis L, Davies I, Gray A, et al. A randomised controlled
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Mynors-Wallis LM, Gath DH, Lloyd-Thomas AR, Tomlinson D.
Randomised controlled trial comparing problem-solving treatment
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Schulberg HC, Block MR, Madonia MJ, et al. Treating major
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Catalan J, Gath DH, Anastasiades P, et al. Evaluation of a brief
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Silverman W. Equitable distribution of the risks and benefits
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effectiveness and efficiency. London: BMJ Publishing Group, 1997:
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Segelov E, Tattersall MHN, Coates AS. Redressing the balance --
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Eichenwald K, Kolata G. Drug trials hide conflicts for doctors.
New York Times, May 16, 1999; 1,28-29.
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Report on consultancy to develop an implementation strategy for
CPGs. Sydney: Royal Australian College of General Practitioners,
August 2, 2000.
School of Psychiatry, University of New South Wales, Sydney, NSW.
Caroline J Hunt, MPsych, PhD, Lecturer (currently, Senior
Lecturer, Department of Psychology, University of Sydney).
Gavin Andrews, MD, Professor.
Clinical Research Unit for Anxiety Disorders, St Vincent's
Hospital, Sydney, NSW.
Louise M Shepherd, BA(Hons), MPsych, Clinical
Reprints will not be available from the authors.
Correspondence: Dr C
J Hunt, Department of Psychology (F12), University of Sydney, NSW,
Make a comment
1: The planned trial
Objective: To compare structured
problem solving with SSRI medication and non-specific counselling for
mild to moderate major depression.
Trial development: The trial was
initially designed with three treatment arms: structured problem solving,
medication and placebo. In 1997, general practitioners in their second
year of a two-year part-time Master of Psychological Medicine course were
approached for feedback. The GPs indicated that, while they believed the
study to be of value, they were uncomfortable with the use of a placebo
control, so the placebo arm of the trial was abandoned. Detailed protocols
for each treatment were developed, with medications which reflected best
prescribing practice (United States Department of Health and Human Services
Clinical practice guidelines 7), a treatment period of six months, and
a follow-up period to track longer-term changes. The protocols were designed
to be simple to use and, to minimise tasks for the GPs, telephone assessments
by a clinical psychologist were planned to confirm diagnosis, assess severity,
and evaluate outcome.
Design: Patients assessed by their
GPs as having mild to moderate major depression were to be randomly allocated
- structured problem solving alone;
- selective serotonin reuptake inhibitor (SSRI) medication and non-specific
- SSRI medication and structured problem solving.
Patients were required to meet International classification of diseases
- 10th revision 8 criteria for a mild or moderate
major depressive episode. Exclusion criteria included current or previous
manic (or hypomanic) or psychotic symptoms, current suicidal intent, current
drug or alcohol abuse, current pharmacological or psychological treatment
for depression, and (to exclude severe depression) current somatic (or
Participating general practitioners:
In 1998, the protocols were again reviewed by students in the Masters
course, who agreed that they were consistent with current best primary
care practice and could be delivered in this setting. Ten GPs agreed to
participate - four were current second-year students in the Masters course,
and six were graduates of the course. Three current second-year students
did not participate because they were not working in general practice,
and two because they did not wish to randomly allocate their patients
to treatment. All participating doctors had been trained in assessing
and managing depression (including structured problem solving), and clinical
supervision was offered over the course of the trial.
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2: Why were no patients recruited?
Six months after commencement of the trial in 1998, despite frequent
reminders and discussions about the trial protocol, no patients had been
recruited. This prompted a clinical audit of all patients with depressive
symptoms attending the participating doctors' practices over three weeks.
Each general practitioner recorded patients presenting with depressive
symptoms and the reasons why they considered them unsuitable for the trial
on a form we designed for this purpose. Over the three weeks, 114 patients
presented with depressive symptoms (12% of all presenting patients), but
none were entered in the study. The results of the audit are shown in
the Table. The most frequently cited reasons for exclusion were current
pharmacological or psychological treatment for depression, or depression
of insufficient severity to meet ICD-10 criteria. In an attempt to improve
recruitment in the following six months, we dropped the exclusion criteria
of current psychological treatment and insufficient severity (these features
now to be assessed by the clinical psychologist), yet still no patients
|Reasons for not entering trial
|| No. (%) patients*
|Depression insufficiently severe to
meet ICD-10 criteria
|Severe depression or criteria met for
|Prior or current manic, hypomanic or
|Serious suicidal intent
|Current drug or alcohol abuse
|| 6 (5.3%)
|Current pharmacological treatment for
|Current psychological treatment for
|Physical problems precluding use of
|Prior failure to respond to an SSRI
|Patient refused randomisation
|General practitioner not confident about
using problem solving with this patient
|Other (eg, dementia, communication difficulties,
| *There were 114 patients,
but general practitioners frequently nominated more than one reason
for excluding patients. ICD-10=International classification of diseases
- 10th revision.8 SSRI=selective serotonin reuptake inhibitor.
|Once the trial was formally abandoned, there were discussions with the
four GPs still completing their Masters course. These GPs admitted unease
with the process of randomisation, despite the demonstrated efficacy of
both treatments for this population.
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