4 October 2009
The Principal Investigators (PIs) for the saMS trial are Professors Rona
Moss-Morris (School of Psychology, University of Southampton) and Trudie
Chalder (Department of Psychological Medicine, Institute of Psychiatry,
King's College London).
Co-researchers are from the Institute of Psychiatry, King's College Londo=
n
and the Chronic Fatigue Unit, Maudsley Hospital, Denmark Hill, London.
The saMS trial is funded by a grant from the UK MS Society:
http://www.mssociety.org.uk/
MS Society page listing further MS clinical/research trials:
http://www.mssociety.org.uk/research/clinical_trials/index.html
There are parallels with the FINE Trial (Fatigue Intervention by Nurses
Evaluation) a randomised controlled trial of nurse led self-help treatmen=
t
for patients in primary care with chronic fatigue syndrome - the sister
trial to the PACE Trial.
Dr Alison Wearden (FINE Trial PI) is cited as a member of the saMS Trial
Steering Committee.
The FINE Trial [ISRCTN74156610] was funded by the Medical Research Counci=
l
(UK), grant number G200212. The FINE Trial has completed but has yet to
publish results. The FINE Trial protocol is also published under Creative
Commons Attribution License: http://www.biomedcentral.com/1741-7015/4/9
Professor Chalder is also working in the area of diabetes, see PubMed:
PMID: 19767547; PMID: 17967704; PMID: 19017589 (with Creed, F). See also=
:
http://www.kingshealthpartners.org/khp/2008/11/21/talking-therapies-can-h=
elp-control-diabetes/
For additional Chalder MS studies, see PubMed: PMID: 19326649; PMID:
18256342 (with Moss-Morris, R), PMID: 19167801 (with Moss-Morris, R)
Professor Moss-Morris works in the area of MS, IBS, CFS, cancer, pain,
psychosomatics and the so-called FSS and MUS.
Professor Moss-Morris was one of the presenters at the Royal Society of
Medicine CFS Conference in April 2008, see: http://wp.me/p5foE-8F for lin=
ks
to RSM video casts and presenter bios (log in required for RSM video
casts).
On Wednesday 6 October 2009, the Royal Society of Medicine is holding a
"Medicine and me" patient event for MS, in association with the MS Trust:
http://www.mstrust.org.uk/
For MS "Medicine and me" conference agenda see:
http://www.rsm.ac.uk/academ/medms.php
The protocol for the saMS Trial is being distributed under the terms of
Creative Commons Attribution License.
[Refer to website for figures, tables and embedded links in the reference
section.]
-----------------------
Abstract PubMed: http://preview.ncbi.nlm.nih.gov/pubmed/19698171
PDF full journal text:
http://www.biomedcentral.com/content/pdf/1471-2377-9-45.pdf
Open Access Text:
BMC Neurol. 2009;9:45.
http://www.biomedcentral.com/1471-2377/9/45
Study protocol
Protocol for the saMS trial (supportive adjustment for multiple sclerosis=
):
a randomized controlled trial comparing cognitive behavioral therapy to
supportive listening for adjustment to multiple sclerosis
Rona Moss-Morris1 , Laura Dennison1 , Lucy Yardley1 , Sabine Landau2 ,
Suzanne Roche3 , Paul McCrone4 and Trudie Chalder5
1 School of Psychology, University of Southampton, Highfield Campus,
Southampton, SO17 1BJ, UK
2 Department of Biostatistics, Institute of Psychiatry, King's College
London, De Crespigny Park, London, SE5 8AF, UK
3 Chronic Fatigue Unit, Maudsley Hospital, Denmark Hill, London, SE5 9RS,
UK
4 Health Service and Population Research Department, Institute of
Psychiatry, King's College London, De Crespigny Park, London, SE5 8AF, UK
5 Department of Psychological Medicine, Institute of Psychiatry, King's
College London, Weston Education Centre, Cutcombe Road, London, SE5 9RJ, =
UK
author email corresponding author email [or contact forms refer to
website]
BMC Neurology 2009, 9:45doi:10.1186/1471-2377-9-45
The electronic version of this article is the complete one and can be fou=
nd
online at: http://www.biomedcentral.com/1471-2377/9/45
Received:15 July 2009
Accepted:23 August 2009
Published:23 August 2009
=A9 2009 Moss-Morris et al; licensee BioMed Central Ltd.
This is an Open Access article distributed under the terms of the Creativ=
e
Commons Attribution License (http://creativecommons.org/licenses/by/2.0),
which permits unrestricted use, distribution, and reproduction in any
medium, provided the original work is properly cited.
Abstract
Background
Multiple Sclerosis (MS) is an incurable, chronic, potentially progressive
and unpredictable disease of the central nervous system. The disease
produces a range of unpleasant and debilitating symptoms, which can have =
a
profound impact including disrupting activities of daily living,
employment, income, relationships, social and leisure activities, and lif=
e
goals. Adjusting to the illness is therefore particularly challenging. Th=
is
trial tests the effectiveness of a Cognitive Behavioural intervention
compared to Supportive Listening to assist adjustment in the early stages
of MS.
Methods/Design
This is a two arm randomized multi-centre parallel group controlled trial.
122 consenting participants who meet eligibility criteria will be randoml=
y
allocated to receive either Cognitive Behavioral Therapy or Supportive
Listening. Eight one hour sessions of therapy (delivered over a period of
10 weeks) will be delivered by general nurses trained in both treatments.
Self-report questionnaire data will be collected at baseline (0 weeks),
mid-therapy (week 5 of therapy), post-therapy (15 weeks) and at six month=
s
(26 weeks) and twelve months (52 weeks) follow-up. Primary outcomes are
distress and MS-related social and role impairment at twelve month
follow-up. Analysis will also consider predictors and mechanisms of chang=
e
during therapy. In-depth interviews to examine participants' experiences =
of
the interventions will be conducted with a purposively sampled sub-set of
the trial participants. An economic analysis will also take place.
Discussion
This trial is distinctive in its aims in that it aids adjustment to MS in=
a
broad sense. It is not a treatment specifically for depression. Use of
nurses as therapists makes the interventions potentially viable in terms =
of
being rolled out in the NHS. The trial benefits from incorporating patien=
t
input in the development and evaluation stages. The trial will provide
important information about the efficacy, cost-effectiveness and
acceptability of the interventions as well as mechanisms of psychosocial
adjustment.
Trial registration
Current Controlled Trials ISRCTN91377356
Background
Psychological adjustment to Multiple Sclerosis
Multiple Sclerosis (MS) is an incurable, chronic and unpredictable diseas=
e
of the central nervous system. The disease is characterized by the
destruction of the myelin sheath surrounding the nerves resulting in the
formation of plaques. These plaques disrupt the transmission of nerve
impulses leading to the symptoms of the illness which include, but are no=
t
limited to, spasticity, loss of balance and co-ordination, blurred or
double vision, blindness, numbness, speech distortions, bladder and bowel
problems, fatigue, pain and cognitive dysfunction [1]. Plaques can occur =
in
a variety of sites resulting in substantial variation in the type and
nature of the symptoms across individuals. The course of the illness is
also highly variable and unpredictable [1]. The majority have either a
relapsing-remitting or a relapsing-progressive course. Patients experienc=
e
periods of partial or total remission where the illness is inactive,
interspersed with symptom relapses. MS can also have a chronic-progressiv=
e
course, in which there is a progressive worsening of symptoms and
disability. Patients may be initially diagnosed with one type of MS, but
over time progress to another.
MS is thought to affect more than 2.5 million people worldwide and around
400,000 people in the United States and 85,000 people in the United Kingd=
om
currently live with the disease [2,3]. The illness is more common in
females than males. The cause of the illness is largely unknown and there
is currently no cure. Treatment focuses on the management of the patient'=
s
symptoms and reducing the number and severity of relapses.
Individuals who have MS are faced with uncertainty about the future,
unpleasant and unpredictable symptoms, treatment regimes and drug side
effects. MS can have profound consequences including disruptions to life
goals, employment, income, relationships, social and leisure activities a=
nd
activities of daily living. Therefore it is not surprising that it poses
multiple challenges for psychological adjustment. A large body of empiric=
al
literature attests to poor adjustment outcomes in MS including elevated
rates of depressive symptomology or distress [4-7], increased anxiety
[5,8], poor subjective well-being and quality of life [5,9], and social
role and relationship difficulties [4,10]. On the other hand, research an=
d
clinical experience suggests that a substantial proportion of people with
MS manage to adapt well to living with the illness [11,12].
Illness factors such as the extent of neurological disability, symptom
severity, remission status and length of illness can influence levels of
adjustment or a sense of well-being and quality of life [13,14]. However,
psychological factors can be as important in predicting and explaining
individual differences in adjustment [14,15]. A systematic review conduct=
ed
as pilot work for this trial demonstrated that a range of psychological
factors were associated with adjustment outcomes in MS [16]. For instance=
,
people reporting high levels of perceived social support showed better
adjustment [17,18], as did individuals with high levels of optimism and
hope [19,20] and those who engaged in health behaviours such as exercise
[21]. Use of problem-focussed coping strategies such as planning was also
consistently associated with more positive outcomes. On the other hand,
emotion-focussed coping strategies including wishful thinking and
escape/avoidance were consistently linked with worse adjustment [22,23].
High perceived levels of stress were also linked to worse adjustment [23].
Similarly, a tendency to interpret events, the illness and MS symptoms in
an overly negative fashion has been linked to worse adjustment [24-26].
Since many of these factors are potentially modifiable through
psychological intervention there is reason to conclude that a programme o=
f
therapy that addresses a number of these factors may lead to improvements
in adjustment.
In the intervention literature to date targets of psychological
interventions for people with MS, particularly Cognitive Behavioral Thera=
py
(CBT), have been mostly centred on the alleviation of depression [27-29].
Two systematic reviews of psychological interventions for MS suggest that
there is some evidence that cognitive behavioural approaches can be
beneficial in the treatment of depression, and in helping people to adjus=
t
to, and cope with having MS[15,30] However, both reviews also criticise t=
he
methodological quality of the intervention studies to date. Many have sma=
ll
sample sizes and many inadequately report details of their intervention a=
nd
trial methodology. This makes it hard to draw definitive conclusions abou=
t
the efficacy of CBT in this area. Both reviews conclude that further,
well-designed trials of CBT-based approaches are warranted. One in
particular, concludes that existing research on adjustment and coping loo=
ks
encouraging and that approaches that target the time period soon after
diagnosis and see adjustment as an ongoing process would be useful [15].
This review also draws particular attention to the importance of followin=
g
the CONSORT statement [31] for reporting such trials and using manuals to
make replication of interventions possible.
Background to the project
Given the evidence that CBT is helpful in improving mental health and
psychological aspects of chronic health conditions, we wanted to
investigate the efficacy of CBT in helping people with MS adjust to the
psychological and social challenges of living with the disease. Although
there are some differences between regional MS services in the United
Kingdom in availability of information, advice and support in the early
stages of MS, formal psychological interventions are not routinely
available.
The aim of this project is to assess whether CBT can enhance the adjustme=
nt
of people in the relatively early years of dealing with MS. Unlike most
previous studies which have evaluated the use of CBT in this group [15,30=
],
the focus of this study is to improve broadly defined adjustment outcomes
rather than restricting the scope of the intervention to reducing
psychiatric morbidity in MS populations where individuals meet criteria f=
or
psychiatric disorder. By focusing the intervention on the earlier years o=
f
MS it is hoped that patients will learn strategies that will assist in
managing the illness in the future.
Because most MS patients receive little structured psychological support,
CBT will be compared to Supportive Listening therapy rather than treatmen=
t
as usual. This will allow us to ascertain whether there are any particula=
r
benefits to CBT or whether just having the opportunity to talk to a
supportive, empathetic therapist can make a difference to adjustment
outcomes. In line with suggestions for research in this area, general
nurses will be trained and supervised to deliver the interventions [15].
Aims
Primary Aim
1) To determine whether patients with early stage MS who undertake an 8
session CBT programme for adjustment to MS will demonstrate better
adjustment (defined as psychological well-being and social and role
adjustment) than those undergoing 8 sessions of Supportive Listening (SL).
Secondary Aims
2) To examine whether the CBT and SL groups differ on a range of secondar=
y
outcomes including quality of life, acceptance of illness and dysfunction=
al
cognitions.
3) To examine whether changes in predefined psychological mechanisms act =
as
mediators through which change/adjustment in our primary outcomes occurs.
These proposed mediating factors are dysfunctional or unhelpful cognition=
s
and behaviours, and acceptance of illness.
4) To examine whether patients' responses to treatment is moderated by
therapeutic alliance factors, patients' treatment preference, engagement =
in
homework tasks, and perceived social support.
5) To examine the cost-effectiveness of both interventions by taking into
account benefits to patients, effects on health service usage and other
costs to society, and cost of providing the interventions.
6) To evaluate both interventions from the perspective of the person with
MS using in-depth interviews and qualitative analysis methods to elicit
their experiences of the therapy, any changes it brought, and any helpful
and unhelpful aspects.
Methods/Design
Design
The trial is a two arm randomized multi-centre parallel group controlled
trial. Consenting participants who meet eligibility criteria are randomly
allocated to receive either CBT for adjustment to MS or Supportive
Listening (SL). The SL arm of the trial has been chosen over standard
medical care as a comparison condition as it is an acceptable and plausib=
le
approach that will control for non-specific treatment factors such as
support, therapist time and attention, and patient expectations of
improvement. The full trial design is summarized in Figure 1.
http://www.biomedcentral.com/1471-2377/9/45/figure/F1
Figure 1. CONSORT flowchart of trial design.
Setting
The trial has two centers (Southampton and South London) and each center
has one therapist who delivers both CBT and SL.
Ethical approval
This study has been reviewed and approved by the Thames Valley Multi-cent=
re
Research Ethics Committee (ref: 07/MRE12/6)
Participants
Sample size calculation
Since there were no available MS CBT trials using either of our primary
outcomes we computed a power analysis calculation based on a recent CBT
trial for depression in people with MS, which used the Beck Depression
Inventory (BDI) as the primary outcome [28]. The BDI, like the GHQ (one o=
f
our primary outcomes) is a measure of affective distress. Using a
conservative estimate for the within-group standard deviation the effect
size from this study was .60. To achieve 80% power at alpha =3D 0.025
significance level (to adjust for two primary outcomes) we would need 55
patients in each group to detect an effect of this magnitude by an
independent samples t-test. To allow for attrition of around 10% at
follow-up we need to initially include 61 participants in each group. In
our CBT for MS fatigue trial we only lost 3/72 patients to follow-up (4%).
Eligibility criteria
Inclusion criteria
Participants do not need to be currently experiencing distress, depressio=
n
or any particular coping difficulties to be included in the study. Howeve=
r,
they must:
- have a definite diagnosis of MS, of any type, confirmed by a neurologis=
t.
- be diagnosed with MS within the last 10 years.
- have some degree of ambulation (with assistance if needed), equivalent =
to
an Expanded Disability Status Scale (EDSS) score [32] of 6.5 or less.
- be stabilised on disease modifying or anti-depressant medication (if
taking). For disease modifying drugs (e.g. interferon) patients must have
been on medication for a minimum of 3 months. For anti-depressants,
patients must be on a stable dose for a minimum of 2 months.
Exclusion criteria
Patients will be excluded from the study if they:
- have gross cognitive impairment that would make participation in 8 one
hour sessions of talking therapy problematic or distressing. This will be
assessed using the Telephone Interview for Cognitive Status-Modified;
TICS-M [33] administered by the trial co-ordinator during screening.
Patients with a score of less than 20 will be excluded.
- have serious psychological disorders for which treatment would be
inappropriate (including psychotic disorders or active substance abuse
problems).
- have other co-morbid serious chronic illnesses (e.g. a malignancy).
- are currently participating in other psychological therapies or have
participated in other therapies within the last 2 months.
- are considered by their treating physician to have needs that are more
appropriately addressed by a referral to another psychological service
(e.g. psychiatrist, clinical psychologist, MS special mental health nurse=
).
Source of participants
Participants will be recruited from two National Health Service (NHS) MS
centers in the Southampton area (Southampton University Hospital Trust;
SUHT) and South London (King's College Hospital Trust; KCHT).
Recruitment and consent process
Patients seen or in contact with these services during the trial period
will be informed about the trial if they appear to meet eligibility
criteria. During routine consultations, either one of the MS nurses or on=
e
of the neurologists will use an eligibility checklist, detailing the key
inclusion and exclusion criteria, to identify suitable patients. The
nurse/neurologist will hand over a Participant Information Sheet with a
contact details reply slip, consent form, and freepost envelope to all th=
at
are potentially eligible and interested. If the participant is keen to be
involved the nurse/neurologist will ask permission to write down the
participant's contact details and freepost it back to the trial
co-ordinator so that she can contact them about the project. Alternativel=
y
the patient can choose to initiate contact with the research team by
posting the contact details form back to the trial co-ordinator, or getti=
ng
in touch by telephone or email.
Once contact is made with the trial co-ordinator the patient's questions
will be answered and their understanding of what is involved in the trial
verified. Consent forms will be returned to the trial co-ordinator by
freepost for those who wish to take part. On the form, participants are
given the choice to consent to the therapy trial and questionnaire
assessments only, or to an additional in-depth telephone interview after
their therapy programme has been completed.
Eligibility screening and enrolment
After obtaining written consent, participants will be screened for
eligibility. Screening will be completed by the trial co-ordinator over t=
he
telephone using a screening checklist of the inclusion/exclusion criteria.
If potential participants do not meet the medication or current/recent
psychological therapy criteria at the time of the eligibility screening
they will be placed on hold and there will be the necessary delay (see
inclusion/exclusion criteria) before they are enrolled into the trial.
After screening, participants will be notified on the telephone by the
trial co-ordinator whether they are eligible or ineligible for the trial.
Baseline questionnaire assessments
Eligible participants will be sent the baseline questionnaire and freepos=
t
return envelope together with a copy of their consent form. The schedule =
of
assessments in the baseline questionnaire and subsequent follow-up
questionnaires is outlined in Table 1.
http://www.biomedcentral.com/1471-2377/9/45/table/T1
Table 1. Details and schedule of saMS trial assessment procedures
Randomization
Randomization is at the patient level and will take place after the
baseline questionnaire has been received. The randomization will be
stratified by centre to ensure equal proportions in each treatment arm.
Randomization is block stratified with varying block sizes. Randomization
will be handled by an independent service at the King's College Mental
Health and Neuroscience Clinical Trials Unit (CTU). On receipt of the
baseline questionnaire, the trial co-ordinator will electronically submit
details of each participant to an electronic randomization system set up
and maintained by the CTU. The system then notifies the relevant
nurse-therapist (i.e. London or Southampton) of the randomisation outcome
by email immediately. This email will be printed and placed on the
participant's therapy file.
Booking in participants
On receiving the randomisation outcome from the CTU the nurse-therapist
will contact the new participant, notify them of their group allocation a=
nd
set a date for their first session. Nurse-therapists will endeavour to bo=
ok
patients within one week of randomisation. Participants will be consulted
about special considerations needed for their visit (e.g. disabled parkin=
g)
and reimbursed for their travel expenses.
Therapist training
The therapists in this trial are two general nurses without prior
experience in delivering psychological interventions, or specialist MS
experience. They were given 2 weeks of intensive classroom training in
understanding MS, CBT and SL.
The training included a combination of didactic teaching, homework
readings, and discussion. Role play and videoed therapy sessions were als=
o
used throughout the CBT and SL training sessions. A summary of the
classroom training package is presented in Table 2.
http://www.biomedcentral.com/1471-2377/9/45/table/T2
Table 2. Details of the two week classroom training program for the
nurse-therapists
The classroom training was followed by 12 weeks of closely supervised
practice with 5 pilot patients. Each nurse saw 3 pilot patients for 8 wee=
ks
of CBT and 2 pilot patients for 8 weeks of Supportive Listening. These
patients had a diagnosis of MS but did not necessarily meet other trial
criteria. RMM supervised the SL and TC and SR supervised the CBT.
Supervision of pilot patients occurred once a week as soon after a sessio=
n
as possible. The supervisor listened to one of the recent sessions and
rated the session using the Therapy Competence and Fidelity Rating scale
modified specifically for this trial [34] This scale includes 14 items, 7
of which assess SL and 7 CBT. Example items are 'Does the therapist refle=
ct
or paraphrase appropriately' (SL) and 'Does the therapist help the client
to identify specific types of cognitive distortions or errors (e.g.
all-or-nothing thinking, over-generalization) (CBT item). The
nurse-therapist also listened to the session and completed self-ratings o=
f
competence using the same rating scale. Supervisor and nurse ratings were
discussed during supervision and strengths highlighted. Areas for
improvements and strategies for these were also identified. Checks were
made for treatment fidelity and to assess that CBT techniques were not us=
ed
in the SL sessions. Approximately midway in the pilot phase of the
training, both supervisors and nurses met to discuss pilot patients and a=
ny
difficulties encountered. Difficult situations were role played and new
skills or ways of managing the situations were practiced.
Establishing Therapist competence
During the pilot/training stage the nurse-therapists audiotaped every
therapy session using digital recorders. The clinical supervisors rated t=
wo
randomly selected recordings (sessions 5, 6, 7 or 8) using the Therapy
Competence and Fidelity Rating scale described above. The therapists were
required to score at least 4 (i.e. a 'acceptable-good' level of competenc=
e
demonstrated) on all the relevant items in order to be deemed competent i=
n
the therapy and ready to commence therapy with trial participants.
Trial interventions
Both therapies will be delivered in 8 sessions over a 10 week period. The
first six sessions will be scheduled weekly and the last two fortnightly.
The first session will be 80-90 minutes long and the remainder will be
between 50 minutes to one hour. The first and fourth sessions will be hel=
d
face-to-face and the remaining six will be telephone sessions. Telephone
sessions make CBT more accessible to patients, particularly those with
mobility problems, and have been shown to be an effective form of therapy
for people with MS [27].
Both interventions will be carried out in accordance with written,
structured manuals. Participants will be issued either a CBT or SL therap=
y
manual in their first session with the nurse-therapist.
CBT
Development of the manual and therapy package
Beck's cognitive model of emotion which incorporates a developmental
perspective [35] in conjunction with a systematic review of 72 studies
which looked at psychological factors associated with adjustment in MS [1=
6]
was used to guide the development of the CBT model and therapy manual for
this trial. Details of our CBT model of adjustment to MS are presented in
the review [16]. Because acceptance of MS appeared to be a significant
factor in adjusting to the illness, we incorporated some basic principles
for facilitating acceptance into our manual from Steven Hayes' Acceptance
and Commitment Therapy [36].
We also conducted two qualitative studies where 30 people with early stag=
e
MS and 15 of their partners engaged in in-depth interviews about their
experiences of having MS, problems they encountered, and the things they
found helpful and unhelpful in adjusting to living with MS [[37]; Denniso=
n,
Yardley, Devereux and Moss-Morris, in preparation]. Transcripts of these
interviews were analysed using thematic analysis. Core themes were covere=
d
in the manual and verbatim quotes from the interviews were used for
illustrating points.
Once the 100 page draft manual was developed, it was reviewed by people
with MS and their families, neurologists, MS nurses and CBT therapists.
Feedback from these sources was then used to make appropriate amendments =
to
the manual.
We also developed a short 10 page booklet for the participant to give to =
a
partner or significant other entitled "Coping when somebody close to you
has MS". This booklet covers information which closely reflects the theme=
s
from the qualitative study on spouses of people with MS [37]. These inclu=
de
dealing with feelings of helplessness and difficult emotions, how to
support someone with MS, dealing with other people's reactions to MS,
maintaining a social life in the face of MS, and finding a balance betwee=
n
looking after your own well-being and the needs of your partner with MS.
The CBT therapy package
The aim of this CBT package is to enable patients to adapt appropriately =
to
their illness. The focus is to achieve optimal day-to-day functioning
within the constraints of the disease, to minimize distress and manage
symptoms in the short and long term. The treatment is structured but also
individualized to the needs of the patient as it is clear from the
literature and our qualitative interviews that the process of adjustment
can vary across individuals.
In the early sessions, participants will work with their nurse-therapist =
in
developing a formulation of their particular areas of strengths and
difficulties. The manual consists of nine chapters which can be used as
appropriate depending on the formulation (see Table 3 for details of the
manualized sessions). The nurse-therapist will work together with the
participant in deciding which areas to focus on and in setting tasks or
homework to do in between the sessions. The nurses will record which of t=
he
nine chapters are covered in each session for each patient. Both nurses a=
nd
patients will work from the same detailed manual.
http://www.biomedcentral.com/1471-2377/9/45/table/T3
Table 3. Summary of the content of the CBT manual for adjustment to MS
Supportive Listening
Supportive Listening (SL) will be presented to patients as a treatment
based on the idea that they will be able to help themselves if given the
opportunity to talk freely, extensively and confidentially about their
experiences, thoughts and feeling about MS and its effect on their lives.
If participants prefer not to focus on their MS, they will be encouraged =
to
choose other topics to talk about which, they feel, are currently relevan=
t
to them.
The SL therapist manual is based on manuals used in previous trials
comparing CBT to counselling [38] and pragmatic rehabilitation to
Supportive Listening therapy [39]. The manual outlines how SL is differen=
t
to CBT and which interventions are prohibited such as offering explanatio=
ns
for symptoms, eliciting symptom information or changes, suggesting explic=
it
coping strategies, interpreting information rather than responding
reflectively, leading or directing the client and giving homework
assignments or tasks.
The SL therapist manual also includes a description of the listening skil=
ls
to be used in SL which are based on the theories and counselling techniqu=
es
of Carl Rogers [40]. These core skills include asking open questions,
active listening skills such as minimal encouragers, paraphrasing,
empathising, reflecting and summarising. The purpose is to provide the
participant the opportunity to talk and express themselves in a
non-judgemental, safe environment. The person should experience empathy
from the therapist and feel listened to.
More advanced Rogerian counselling skills such as problem clarification,
accurate understanding and challenging are not included in the therapist
training or manual. The SL was designed to control for the non-specific
effects of therapy such as warmth and positive regard rather than being
formal counselling therapy per se.
The participant or client manual for SL is a short 7 page document. It
provides brief information about MS and why Supportive Listening may be
beneficial for people with MS. It also outlines what patients can expect
from the therapy sessions and a timetable for scheduling the meetings.
Missed or postponed sessions
In the case of cancellation or non-attendance at therapy the
nurse-therapist will contact the participant by telephone to ascertain th=
e
problem of attendance and will discuss an appropriate solution. If the
session can be rearranged to stay in line with the standard scheduling of
sessions it should be rescheduled.
Inevitably there will be times when MS symptoms or relapse, other sicknes=
s,
holidays, or unexpected events interfere with the standard scheduling of
sessions such that therapy exceeds or alters the 10 week window (describe=
d
earlier). However, generally therapy should be completed within a maximum
of 12 weeks. In exceptional circumstances (e.g. the participant experienc=
es
a severe relapse of MS or has a family/personal crisis) timing of session=
s
can be discussed with principal investigators and rearranged. However, a
participant will never have more than the 8 sessions.
Therapy record keeping
Deviations from the standard therapy schedule will be logged so they can =
be
reported and analysed. Details of the date and length of each session (an=
d
for CBT participants, the chapters covered and a rating on a scale of 1-1=
0
of homework engagement) will be recorded by the nurse-therapist.
All therapy sessions will be digitally recorded with permission from the
participant and saved in an encrypted anonymous format. These recordings
will be used for ongoing supervision and to assess treatment fidelity and
therapist effects at the end of the trial.
Informing the participants' health professionals regarding involvement in
the trial
After the first session, the nurse-therapist will write to the
participant's GP and MS service to inform them of the patient's
participation in the trial. For CBT patients this will also include a
summary of the assessment made and the areas that are likely to be
concentrated on in the remaining sessions (discussed and agreed with the
participant and a copy sent to the participant for their own records).
Ongoing supervision of nurse-therapists
Two experienced CBT therapists (SR and TC) will supervise the CBT and an
experienced health psychologist (RM) will supervise the SL. For the first
two months of the trial each nurse-therapist will have a separate CBT and
SL supervision session once per week. Supervision will be fortnightly for
the rest of the trial. Sessions will be between 30 - 60 minutes long and
may be either by telephone, or face-to-face. At least once every two mont=
hs
the nurse-therapists will have a face-to-face session. Tape recordings of=
a
session will be shared with the supervisor before the sessions and
discussed during supervision. Each nurse-therapist will keep a log of dat=
es
and timings of their supervision sessions. Once per month the supervisor
will check that session documentation has been properly completed.
Therapeutic fidelity ratings
Fidelity rating for the interventions will occur throughout the trial in
the supervision sessions. In addition, at the end of the trial a selectio=
n
of recordings of therapy sessions will be assessed by an independent
experienced clinician using a modified version of the therapy rating scal=
e
[34] to ensure treatment integrity. Sessions to be rated will be selected
at the end of the therapy part of the trial without input from nurses and
supervisors. Approximately one third (randomly chosen) will be co-rated b=
y
a second rater in order to establish reliability of ratings.
Outcome assessments
Questionnaires (see Table 1) will be completed at baseline (prior to
randomisation), mid-therapy (session 5 of therapy sessions), post-therapy
follow-up (15 weeks after randomisation), 6 month follow-up (26 weeks aft=
er
randomisation) and 12 month follow-up (52 weeks after randomisation). All
assessments are questionnaire-based. Data collection will be managed by t=
he
trial co-ordinator who will be blind to treatment allocation. Participant=
s
will be able to choose whether to complete online or paper-based
questionnaires (returned by freepost). Dates that questionnaires are sent
out and received will be recorded. A reminder phone call or reminder emai=
ls
will be used if the questionnaire is not received within two weeks of
send-out. After four weeks another copy of the questionnaire pack will be
reissued.
If participants are unable to complete questionnaires themselves (e.g. du=
e
to relapse) the trial co-ordinator will go through the questionnaire on t=
he
telephone and this will be logged as such on the trial database.
Spouses/partners/friends will not be allowed to complete the questionnair=
e
on the participant's behalf or assist them with writing their answers.
Completed, returned questionnaires will be checked by the trial
co-ordinator and participants contacted if there is a large amount of
missing data.
Primary outcome measures
There are two primary outcomes.
1. The General Health Questionnaire (GHQ) [41] is designed to measure
general levels of distress in people in the community and medical setting=
s.
The measure is uncontaminated by the experience of MS related somatic
symptoms and a recent study showed the GHQ was the most treatment
responsive measure of psychological distress in three discrete MS samples
[42].
2. The Work and Social Adjustment Scale (WSAS) [43] is a self-report scal=
e
of functional impairment attributable to an identified illness, in this
case MS. The scale measures how much MS interferes with a person's work,
home management, social leisure activities, private leisure activities, a=
nd
the ability to form and maintain close relationships.
Secondary outcome measures
These include quality of life and factors which have been shown to be
related to adjustment outcome in MS and are key components of our model o=
f
adjustment to MS.
1. Quality of life will be measured using the EuroQol 5 (EQ-5D) [44] whic=
h
is a 5-item composite measure of mobility, self-care, usual activities,
pain/discomfort and anxiety/depression.
2. Acceptance of illness will be measured using the Acceptance of Chronic
Health Conditions Scale (ACHC) [45]. This scale assesses acceptance of an=
d
adjustment to change in one's life due to a chronic health condition (in
this case MS).
3. Dysfunctional cognitions will be measured by the Psychological
Vulnerability Scale (PVS) [46]. This short scale taps maladaptive cogniti=
ve
responses which are proposed to promote unhelpful adjustment to stressors
(e.g. perfectionism, need for approval).
Mediators of the treatment effect
In order to gain a clearer idea of the possible mechanisms and to help
refine our CBT model of MS adjustment we have included a number of measur=
es
as possible mediators of the treatment effect. These are cognitive
behavioural factors which have been demonstrated to be associated with
adjustment outcomes, and/or are addressed within either or both
interventions. We hypothesize that the mediators of improvements in
psychological well-being (GHQ) will be different to the mediators of
improvements in functional impairment (WSAS).
Mediators of the WSAS
1. Cognitive and behavioural responses to symptoms. The Cognitive and
Behavioural Response to Symptoms Questionnaire (CBRSQ) [Moss-Morris,
Chalder, Skerrett & Baldwin, in preparation] is a newly devised 34 item
questionnaire which was designed to measure patients' cognitive and
behavioural responses to symptoms. The subscales of this questionnaire ha=
ve
been shown to predict a significant amount of the variance in MS related
disability and fatigue over and above EDSS scores, remission status, and
mood [47]
2. Illness perceptions will be assessed using the Brief Illness Perceptio=
ns
Questionnaire (BIPQ) [48]. This 8 item questionnaire assesses cognitive a=
nd
emotional illness representations (e.g. its timeline, consequences,
controllability). Across a range of illnesses, negative illness perceptio=
ns
are related to worse adjustment outcomes, whilst changes to illness
perceptions may improve adjustment.
Mediators for GHQ
1. Unhelpful beliefs about emotions are measured using the recently
developed Beliefs About Emotions Scale (BES) [Rimes & Chalder; in
preparation]. This 6 item questionnaire measures the extent to which the
person holds unhelpful beliefs about experiencing, expressing, and
controlling emotions.
2. Dysfunctional cognitions (PVS)[46] as described above under secondary
outcomes.
3. Acceptance of illness (ACHC) [45]as described above.
Moderators of Treatment Improvement
We will also look at two potential moderators of patients' response to
treatment, the therapeutic alliance and perceived social support.
The therapeutic alliance is measured using the Alliance subscale of the
Therapy Competence and Fidelity Rating scale [34]. Independent raters bli=
nd
to treatment outcome will use this scale to rate therapy tapes from each =
of
the two therapists. The scale includes items including emotional expressi=
on
by the patient and level of empathy expressed by the therapist. Items are
rated on a 7-point Likert Rating Scale, with anchors at four points along
the scale [e.g. 'not at all' (1), 'somewhat' (3), 'considerably' (5) and
'extensively'].
Social support is measured by the Significant Other Scale (SOS) [49]. We
are using a shortened version of this scale (8 items) where the participa=
nt
is asked to state one key support person and then rate desired and receiv=
ed
support in different domains (e.g. practical help and socialising).
In addition to these measures we have included a number of questions to
measure illness severity, progression and relapse (see Table 1) including
the self-reported Expanded Disability Status Scale (EDSS)[50]. This will
allow us to assess whether there has been any noticeable disease
progression. The self-reported EDSS is a relatively new instrument which
allows MS patients to self-report their current disease status, rather th=
an
this being assessed by a neurologist during a clinical examination. The
questionnaire includes items which relate to mobility, strength,
co-ordination, sensation, bladder, vision, speech, swallowing, and
cognition. Using the responses from these items, functional system scores
are computed and an EDSS score is assigned to the participant ranging fro=
m
0 (no neurological impairment) to 10 (death from MS). The trial
co-ordinator will review and score each questionnaire, which is then
co-scored by a neurologist specialising in MS in order to ensure
reliability of scoring.
Patients will also be asked to rate their treatment preference at the
beginning of the trial and their feelings about treatment efficacy at the
end of the trial.
Service use and QALYs
Service use (additional to the CBT intervention or Supportive Listening
which will both be centrally recorded) by patients in both arms of the
trial will be measured using the Client Service Receipt Inventory (CSRI)
[51]. This will record health and social service contacts in the six mont=
hs
prior to baseline assessment, and the periods prior to 6- and 12-month
follow-up interviews. Time lost from work because of MS-related problems
will also be measured.
The EuroQol (EQ-5D) [44], a 5 item composite measure which considers
mobility, self-care, usual activities, pain/discomfort and
anxiety/depression will be used to assess quality of life. The EQ-5D will
be used to generate quality adjusted Life Years (QALYs) [52].
Blinding
The trial co-ordinator will administer all quantitative assessment
procedures and will be kept blind to the treatment allocation of
participants until final follow-up has been completed. The trial
co-ordinator will not deal with paperwork that links a participant to the=
ir
therapy condition, or be present when any discussions revealing this
information take place. However, if she becomes aware or suspicious of th=
e
treatment condition of any participant she will log this lapse of blindin=
g
on the trial database for later consideration in a sensitivity analysis.
Either way, as all assessments are by self-report, rather than rated by a
member of the research team, influences of observer biases are not
expected.
Due to the nature of the interventions it is not possible to blind the
principal investigators and nurse-therapists as they will be delivering a=
nd
supervising the therapy sessions. It is also not possible to blind
participants to treatment allocation. However, the trial is set up as
comparison of two treatments rather than as a treatment versus control
condition. The participant information presents both treatments as a way =
of
assisting adjustment to MS with neither treatment being given preference.
During statistical analysis the treatment groups will be assigned a code
rather than their name so that the statisticians are unaware what the
treatment group code represents.
Data inputting
Data will be input into a flat SPSS spreadsheet by the trial co-ordinator.
All primary data (GHQ and WSAS) at all time points will be double entered
by an administrator. This will then be checked for errors and
discrepancies, which will then be corrected by consulting the raw
questionnaire data (paper based or online). A percentage of all other dat=
a
inputting will also be double entered to ensure accuracy. Any follow-up
action (e.g. double entry of more data) will be taken as necessary.
Qualitative interviews
On receipt of completed post-therapy questionnaires, details of those
participants who have consented to take part in the in-depth interview wi=
ll
be passed to a post-doctoral researcher who has not had any involvement i=
n
other aspects of the trial.
Around 15 CBT participants and 15 SL participants will be interviewed
regarding their experiences of therapy. If a large enough pool of
consenting participants is available, purposive sampling will be employed
on the basis of questionnaire-based reports of therapy satisfaction,
perceived improvement, and demographic and illness characteristics.
The interviewer will contact each participant to schedule a telephone
interview and conduct the interview according to an interview schedule.
Questions address expectations of therapy, experiences of therapy session=
s,
features of therapy liked and disliked, and the process of change (or not=
)
as a result of therapy. Each interview will be audio-taped or digitally
recorded. Interviews will be transcribed by an administrator, omitting an=
y
information that may compromise confidentiality. Completed recordings and
transcripts will be stored in a locked cabinet (if printed) or in a
password protected file (if digital) for analysis after the trial has
concluded.
Independent monitoring and quality control
A Trial Steering Committee (TSC) including a Data Monitoring Group has be=
en
set up to monitor the conduct of the trial. They will provide overall
supervision for the trial and safeguard its integrity. Authority for
continuation of the trial lies with the TSC. The committee includes an
independent chairperson, the lead and principal investigators, the trial
co-ordinator, a statistician, a representative from the MS Society and a
patient representative. The committee will meet at least annually during
the trial period, and more frequently and/or via telephone conference or
email communication if pressing issues arise.
Compliance
The trial will be conducted in compliance with the Declaration of Helsink=
i,
MRC Good Clinical Practice (GCP) guidance, the Data Protection Act (1998)=
,
the National Research Ethics Service (NRES) approvals, NHS Trust
regulations, and other regulatory requirements as appropriate. The final
trial publication will include the items recommended under the extended
CONSORT statement for randomized trials of nonpharmacologic treatment [53=
].
Participant safety
Both CBT and SL are expected to be of low risk to participants. They are
non-invasive talking therapies and similar interventions have been
previously used in chronic illness populations. If the nurses are concern=
ed
about a patient's safety, particularly if they believe the person may be
vulnerable to self-harm, they immediately contact one of the therapy
supervisors who will telephone the patients to assess the severity of the
situation. If necessary, a referral will be made to ensure the patient ge=
ts
the support they need.
Adverse events/reactions
Adverse events (AE), adverse reactions (AR), serious adverse events (SAE)
and serious adverse reactions (SAR) will be defined according to the usua=
l
clinical trial definitions. Where these occur they will be recorded on th=
e
trial spreadsheet and reported to the appropriate authorities and followe=
d
up in the standard manner.
Stopping/discontinuation rules
Departures from the trial protocol, changes to the manualized treatments,
and breaking of the randomization code will only occur with the advice of
the TSC if it becomes apparent that a particular treatment arm is causing=
a
consistent pattern of deterioration, or if there is another obvious and
significant clinical necessity.
Withdrawals from therapy
If a participant expresses the wish to withdraw from the trial, the
nurse-therapist will contact the participant to ascertain the reason for
drop-out if the participant is willing to share this. They will be offere=
d
the option of talking to a principal investigator instead if they wish. I=
f
the participant considers that they are deteriorating a principal
investigator will contact them and discuss an appropriate solution.
The nurse-therapist (or principal investigator if they make contact) shou=
ld
ascertain whether consent is withdrawn from:
a) further treatment only
b) further treatment and follow-up (questionnaires plus the in-depth
telephone interview)
c) retaining data already collected for use in final analysis.
The reason for withdrawal (e.g. adverse events, relapse, illness
progression, inability to adhere, inability to attend) will be communicat=
ed
to the principal investigator for that centre as well as the trial
co-ordinator who will record and report this information as appropriate.
If it is felt that a participant should be withdrawn from the trial this
will be discussed with the nurse-therapist, principal investigator and
clinical supervisor. One of the principal investigators will assess the
participant clinically within a week and arrange appropriate ongoing care.
The nurse-therapist will write to the participant's GP and MS service to
confirm withdrawal from treatment.
Statistical analysis plan
Statistical analysis will be carried out in SPSS and/or Stata general
purpose statistical analysis packages. Mediation modeling may require use
of specialist structural equation modeling software (e.g. AMOS or M-Plus).
All treatment group comparisons will be carried out on an
intention-to-treat basis, that is subjects will be analyzed in the group =
to
which they were randomized irrespectively of the treatment received. The
primary and secondary longitudinal outcomes will be analyzed using linear
mixed modeling. In these models the outcome variable at the post-treatmen=
t
time points will be the dependent variable and baseline values of the
outcome variable, centre, time (post-treatment, 6 M follow-up or 12 M
follow-up), group (CBT or Supportive Listening) and a time =D7 group
interaction terms will feature as explanatory variables. To account for
correlation between measures taken on the same individual at various time
points subject-varying random intercepts and slopes of time will also be
included in the model. Further baseline variables might be used as
explanatory variables, to provide more powerful group comparisons if they
are found to be predictive of the outcome variable. As the model fitting
will by maximum likelihood such analyses are valid if missing data arises
at random (MAR). The effect of informative missingness processes will be
explored by means of a formal sensitivity analysis [54].
We will further investigate whether results were unduly influenced by
patients who have shown marked disease progression during the trial or wh=
o
have altered medication during the trial period. We will also assess the
sensitivity of the results to excluding patients who did not receive a
sufficient number of treatment sessions or those who had low expectations
of the therapy they received.
An approach similar to Baron and Kenny's mediation modeling [55]will be
used to explore whether change of psychological outcomes mediates the pat=
h
from therapy to change in MS adjustment. Specifically we will use
instrumental variable methods advocated by Dunn and colleagues to try and
adjust for unobserved confounders of the path from mediations to outcomes
[56,57].
Economic evaluation plan
Service use measured with the CSRI will be combined with relevant unit
costs (e.g. [58]). The cost of the interventions will be calculated using
information on therapist pay as well as training and supervision costs an=
d
overheads. Cost comparisons will be made between the two groups using
bootstrapping methods to account for non normality in the data
distribution.
Service cost data will be combined with the primary outcome measures (GHQ
and WSAS) and quality-adjusted life years (QALYs), generated from the EQ-=
5D
to assess cost-effectiveness. If the intervention has lower costs and
better outcomes then it will be 'dominant'. In the event of the
intervention having higher service costs and better outcomes,
cost-effectiveness will be assessed using incremental cost-effectiveness
ratios. To address uncertainty in cost and outcome differences we will us=
e
cost-effectiveness planes (CEPs) which will show the probability of the
intervention being (i) cost-saving and more effective, (ii) cost-saving a=
nd
less effective, (iii) cost-increasing and more effective and (iv)
cost-increasing and less effective. Cost-effectiveness acceptability curv=
es
(CEACs) will be generated to show the probability that the intervention i=
s
cost-effective for different values placed on a unit improvement in the
GHQ/WSAS or one extra QALY gained. CEPs will involve producing a large
number of cost-outcome combinations using bootstrap methods and plotting
these on a plane where one axis represents incremental costs and the othe=
r
incremental outcome. CEACs will be generated by computing 'net benefits'
for each participant (defined as the monetised value of outcome minus
service costs). The value of a unit improvement in outcome is unknown and
therefore a range of values will be used resulting in a number of differe=
nt
net benefits for each participant. Regression analyses will be used to
estimate the difference in net benefits between the two arms for each val=
ue
placed on a unit improvement in outcome. Bootstrapped regression
coefficients of these differences will be saved and the proportion that a=
re
above zero will indicate the probability that one arm is more
cost-effective than the other.
Qualitative analysis plan
A thematic analysis of the participants' therapy experience interviews wi=
ll
be conducted based upon procedures described by Boyatzis and Joffe and
Yardley [59,60]. This will involve an inductive approach whereby
transcripts are coded in order to develop conceptual categories which
describe salient themes in the data. Elements of grounded theory practice
[61,62] will also be incorporated; constant comparison, "in vivo" coding,
attention to discrepant cases and memoing. Once all transcripts are coded
and a comprehensive coding manual has been developed and refined we will
inspect the data for patterns and relationships in the themes within and
between the two therapy groups.
Reporting and Dissemination
A number of publications are expected from this trial including:
. Main outcome paper
. Economic analysis-costs/benefits
. Qualitative analysis of patient feedback and experiences
. Predictors of treatment outcome
. Mechanisms of change during therapy
. Cross-sectional study of factors involved in adjustment from baseline
data
We expect to present the findings at various scientific forums including =
MS
specific and neurology conferences, health and clinical psychology
conferences, and behavioural medicine meetings. We will also report back =
to
our funder the MS Society and patient led meetings such MS Life. A lay
summary of the results will be sent to trial participants.
Study status
The trial opened to recruitment in January 2008. Enrolment and the therap=
y
interventions will continue until early 2009. Throughout 2009 follow-up
assessments of participants will be conducted. Results will be analyzed a=
nd
reported in 2010.
Discussion
To our knowledge this is the first RCT to look specifically at assisting
with broadly defined psychological adjustment in the early stages of the
MS. The relatively inclusive eligibility criteria for this trial mean tha=
t
we are offering therapy to a group of patients who would not otherwise
routinely have any formal psychosocial interventions, but who nonetheless
are faced with considerable adjustment challenges.
This trial will answer important questions about the efficacy of an 8
session manualized CBT treatment in reducing distress and MS-related soci=
al
and role impairment as well as a number of secondary outcomes. It has a
relatively long follow-up period (12 months) which allows for the
assessment of both short and longer-term effects of the interventions. Th=
e
trial will also provide important data regarding the cost-effectiveness o=
f
both interventions and their acceptability to patients. The trial is also
set up in such a way to study mediators of change during therapy and
therefore shed light on the process of adjustment and the important facto=
rs
involved.
If the CBT (or indeed the SL) is an efficacious and cost-effective
intervention for assisting with adjustment to MS, the fact that it has be=
en
manualized and the details of training, supervision and therapy delivery
are intricately described means that it should be straightforward to
replicate on a larger scale. The use of general nurses as therapists in
this trial is a significant advantage. If therapy can be successfully
learned and delivered by general nurses with no prior experience of
psychological interventions, it suggests that it would not be necessary t=
o
employ health professionals with high-level training in clinical psycholo=
gy
(who are in short supply and expensive to services) to deliver adjustment
interventions to those with MS. Indeed, they could potentially be offered
by health professionals who are already working with MS patients in the N=
HS
(e.g. specialist MS nurses and occupational therapists). Furthermore, the
use of telephone contact for the majority of the therapy sessions means
that the intervention could be delivered in a flexible way that could rea=
ch
more patients. Mobility difficulties and other disabling and unpredictabl=
e
symptoms might be significant barriers for people with MS accessing
face-to-face services.
The trial is set up to be methodologically robust and to conform to best
practice for the conduct and reporting of RCTs. We have taken care to
address key sources of bias; the manualized therapies are subject to
ongoing supervision to ensure therapy fidelity and this will also be
checked post-therapy by independent raters. The assessments of patient
outcomes are self-reported and collected by the trial co-ordinator who is
blind to treatment allocation and uninvolved in therapy delivery. The CBT
is being exposed to a stringent test of it's efficacy since it is being
compared to a potentially therapeutic intervention, SL. Although the SL i=
s
designed to control for non-specific therapeutic effects such as of the
considerable time and attention from an interested and caring health
professional, it is based on principles of counseling which allows patien=
ts
to explore and work through issues is a non-directive format.
The saMS trial benefits from patient user input from the early stages of
therapy design and manual development, right through to the in depth
evaluation of the therapy sessions. The use of qualitative methods
alongside the RCT means that the voice of those who would be using the
intervention has been considered during both the design and evaluation of
the therapy. This qualitative data will be particularly important in
guiding any changes to the therapy format.
Competing interests
The authors declare that they have no competing interests.
Authors' contributions
RM and TC were involved in the conception and design of the study and
applied for funding. RM wrote the initial grant, is the lead investigator
and the Principal Investigator for the Southampton site, supervises the S=
L
therapy and led the write up of the protocol. TC is the Principal
Investigator for the London site. LY developed the idea for and supervise=
d
the qualitative studies and assisted in the initial grant application. LD
helped develop and refine the study protocol, co-ordinates the trial, and
has had significant input into the write-up of the protocol. SR contribut=
ed
to the training and competency assessment of the therapists, conducts
ongoing supervision of the CBT therapy and contributed to these sections =
of
the manuscript .SL developed the statistical analysis plan. PM developed
the economic analysis plan. All authors read and approved the final versi=
on
of the manuscript.
Acknowledgements
This project was funded by a grant from the UK MS Society.
Thank you to the nurse-therapists Sarah Morton and Sally Baynes.
Thank you also to our colleagues at the NHS MS Services at Southampton
University Hospital Trust and King's College Hospital Trust: Alan Turner,
Chris Halfpenny, Ian Galea, Sheila Chartres, Jane Ware, Jane Cameron, Haz=
el
Daniel, Stephanie Heath, Eli Silber, Joan Regan, Pauline Shaw, Fiona Barn=
es
and Sally Jones.
Thank you to the independent members of our Trial Steering Committee:
Alison Wearden, Charlie Bloom, Rebecca Walwyn and Ed Holloway.
References
1 Robinson I: Multiple Sclerosis. London: Routledge; 1988.
2 National MS Society: Who gets MS? 2009
http://www.nationalmssociety.org/about-multiple-sclerosis/who-gets-ms/ind=
ex.aspx
3 UK MS Society: What is MS? 2009
http://www.mssociety.org.uk/about_ms/what_is_ms/index.html
4 Hakim EA, Bakheit AMO, Bryant TN, Roberts MWH, McIntosh-Michaelis SA,
Spackman AJ, Martin JP, McLellan DL: The social impact of multiple
sclerosis-a study of 305 patients and their relatives. Disability and
Rehabilitation 2000, 22:288-293. PubMed Abstract | Publisher Full Text
5 Janssens A, van Dorn P, de Boer J, Meche F, Passchier J, Hintzen R:
Impact of recently diagnosed multiple sclerosis on quality of life,
anxiety, depression and distress of patients and partners. Acta
Neurologica Scandinavica 2003, 108:389-395. PubMed Abstract | Publisher
Full Text
6 Patten SC, Metz LM: Depression in Multiple Sclerosis. Psychotherapy and
Psychosomatics 1997, 66:286-292. PubMed Abstract
7 Siegert RJ, Abernethy DA: Depression in multiple sclerosis: a review.
Journal of Neurology, Neurosurgery and Psychiatry 2005, 76:469-475.
Publisher Full Text
8 Zorzon M, de Masi R, Nasuelli D, Ukmar M, Pozzi Mucelli R, Cazzato G,
Bratina A, Zivadinov R: Depression and anxiety in Multiple Sclerosis: a
clinical and MRI study in 95 subjects. Journal of Neurology 2001,
248:1432-1459. Publisher Full Text
9 Benito-Leon J, Morales MJ, Rivera-Navarro J, Mitchell A: A review about
the impact of multiple sclerosis on health-related quality of life.
Disability and Rehabilitation 2003, 25:1291-1304. PubMed Abstract |
Publisher Full Text
10 Mohr DC, Dick PP, Russo D, Pinn J, Boudewyn AC, Likosky W, Goodkin DE:
The Psychosocial Impact of Multiple Scleoris: Exploring the Patient's
Perspective. Health Psychology 1999, 18:376-382. PubMed Abstract |
Publisher Full Text
11 Antonak RF, Livneh H: Psychosocial adaptation to disability and its
investigation among persons with multiple sclerosis. Social Science and
Medicine 1995, 40:1099-1108. PubMed Abstract | Publisher Full Text
12 Brooks NA, Matson RR: Social-psychological adjustment to multiple
sclerosis. A longitudinal study. Social Science & Medicine 1982,
16:2129-2135. Publisher Full Text
13 Chwastiak L, Ehde DM, Gibbons LE, Sullivan M, Bowen JD, Kraft GH:
Depressive symptoms and severity of illness in multiple sclerosis:
Epidemiologic study of a large community sample. Am J Psychiatry 2002,
159:1862-1868. PubMed Abstract | Publisher Full Text
14 McIvor G, Rikland M, Reznikoff M: Depression in multiple sclerosis as =
a
function of length and severity of illness, age, remissions, and perceive=
d
social support. Journal of Clinical Psychology 1984, 40:1028-1033. PubMed
Abstract | Publisher Full Text
15 Thomas PW, Thomas S, Hiller C, Galvin K, Baker R: Psychological
interventions for multiple sclerosis. Cochrane Database of Systematic
Reviews 2006, 1:CD004431.
16 Dennison L, Moss-Morris R, Chalder T: A review of psychological
correlates of adjustment in patients with multiple sclerosis. Clinical
Psychology Review 2009, 29:141-153. PubMed Abstract | Publisher Full Text
17 McCabe MP, McKern S, McDonald E: Coping and psychological adjustment
among people with multiple sclerosis. Journal of Psychosomatic Research
2004, 56:355-361. PubMed Abstract | Publisher Full Text
18 Schwartz C, Frohner R: Contribution of demographic, medical, and socia=
l
support variables in predicting the mental health dimension of quality of
life among people with multiple sclerosis. Health Soc Work 2005,
30:203-212. PubMed Abstract
19 de Ridder D, Schreurs K, Bensing J: The relative benefits of being
optimistic: Optimism as a coping resource in multiple sclerosis and
Parkinson's disease. British Journal of Health Psychology 2000, 5:141-155.
Publisher Full Text
20 Patten SB, Metz LM: Hopelessness ratings in relapsing-remitting and
secondary progressive multiple sclerosis. International Journal of
Psychiatry in Medicine 2002, 32:155-165. PubMed Abstract | Publisher Full
Text
21 Stuifbergen AK, Blozis SA, Harrison TC, Becker HA: Exercise, functiona=
l
limitations, and quality of life: A longitudinal study of persons with
multiple sclerosis Archives of Physical Medicine & Rehabilitation 2006,
87:935-943. Publisher Full Text
22 Aikens JE, Fischer JS, Namey M, Rudick RA: A replicated prospective
investigation of life stress, coping, and depressive symptoms in multiple
sclerosis. Journal of Behavioral Medicine 1997, 20:433-445. PubMed Abstra=
ct
| Publisher Full Text
23 Pakenham KI: Adjustment to multiple sclerosis: application of a stress
and coping model. Health Psychology 1999, 18:383-392. PubMed Abstract |
Publisher Full Text
24 Bruce JM, Polen D, Arnett PA: Pain and affective memory biases interac=
t
to predict depressive symptoms in multiple sclerosis. Multiple Sclerosis
2007, 13:58-66. PubMed Abstract | Publisher Full Text
25 Kneebone II, Dunmore EC, Evans E: Symptoms of depression in older adul=
ts
with multiple sclerosis (MS): comparison with a matched sample of younger
adults. Aging & Mental Health 2003, 7:182-185. PubMed Abstract | Publishe=
r
Full Text
26 Shnek ZM, Foley FW, LaRocca NG, Gordon WA, DeLuca J, Schwartzman HG,
Halper J, Lennox S, Irvine J: Helplessness, self-efficacy, cognitive
distortions, and depression in multiple sclerosis and spinal cord injury.
Annals of Behavioral Medicine 1997, 19:287-294. PubMed Abstract | Publish=
er
Full Text
27 Mohr D, Likosky W, Bertagnolli A, Goodkin D, Wende J, Dwyer P, Dick L:
Telephone-administered cognitive-behavioral therapy for the treatment of
depressive symptoms in multiple sclerosis. Journal of Consulting and
Clinical Psychology 2000, 68:356-361. PubMed Abstract | Publisher Full Te=
xt
28 Mohr D, Boudewyn A, Goodkin D, Bostrom A, Epstein L: Comparative
outcomes for individual cognitive-behavior therapy, supportive-expressive
group psychotherapy, and Sertraline for the treatment of depression in
multiple sclerosis. Journal of Consulting and Clinical Psychology 2001,
69:942-949. PubMed Abstract | Publisher Full Text
29 Mohr D, Hart S, Julian L, Catledge C, Honos-Webb L, Vella L, Tasch E:
Telephone-administered psychotherapy for depression. Archives of General
Psychiatry 2005, 62:1007 1014. PubMed Abstract | Publisher Full Text
30 Malcomson KS, Dunwoody L, Lowe-Strong AS: Psychosocial interventions i=
n
people with multiple sclerosis: a review. Journal of Neurology 2007,
254:1-13. PubMed Abstract | Publisher Full Text
31 Altman DG, Schulz KF, Moher D, Egger M, Davidoff F, Elbourne D, Gotzsc=
he
PC, Lang T, for the CONSORT Group: The revised CONSORT statement for
reporting randomized trials: Explanation and elaboration. Ann Intern Med
2001, 134:663-694. PubMed Abstract | Publisher Full Text
32 Kurtzke J: Rating neurological impairment in multiple sclerosis: an
expanded disability status scale (EDSS). Neurology 1983, 33:1444-1452.
PubMed Abstract
33 Brandt J, Welsh K, Breitner J, Folstein M, Helms M, Christian J:
Hereditary influences on cognitive functioning in older men; a study of
4000 pairs. Archives of Neurology 1993, 50:599-603. PubMed Abstract |
Publisher Full Text
34 Godfrey E, Chalder T, Ridsdale L, Seed P, Ogden J: Investigating the
'active ingredients' of cognitive behaviour therapy and counselling for
patients with chronic fatigue in primary care: developing a new process
measure to assess treatment fidelity and predict outcome. British Journal
of Clinical Psychology 2007, 46:253-272. PubMed Abstract | Publisher Ful=
l
Text
35 Beck AT: Cognitive therapy and the emotional disorders. New York:
Penguin Books; 1976.
36 Hayes SC, Follette VM, Lineham M: Mindfulness and acceptance: Expandin=
g
the cognitive behavioral tradition. New York: The Guilford Press; 2004.
37 Bogosian A, Moss-Morris R, Yardley L, Dennison L: Experiences of
partners of people in the early stages of multiple sclerosis. Multiple
Sclerosis 2009, 15:876-884. PubMed Abstract | Publisher Full Text
38 Risdale L, Godfrey E, Chalder T, Seed P, King M, Wallace P, Wessely S:
Chronic fatigue in general practice: is counselling as good as cognitive
behaviour therapy? A UK randomised trial. British Journal of General
Practice 2001, 51:19-24. PubMed Abstract | Publisher Full Text | PubMed
Central Full Text
39 Wearden AJ, Riste L, Dowrick C, Chew-Graham C, Bentall RP, Morriss RK,
Peters S, Dunn G, Richardson G, Lovell K, et al.: Fatigue Intervention b=
y
Nurses Evaluation - The FINE Trial. A randomised controlled trial of nurs=
e
led self-help treatment for patients in primary care with chronic fatigue
syndrome: study protocol. [ISRCTN74156610]. BMC Medicine 2006, 4:9. PubMe=
d
Abstract | BioMed Central Full Text | PubMed Central Full Text
40 Rogers C: Client-centered therapy: its current practice, implications
and theory. London: Constable; 1951.
41Goldberg D: General Health Questionnaire (GHQ-12). Windsor, NFER-NELSON=
;
1992.
42 Hobart J, Riazi A, Lamping D, Fitzpatrick R, Thompson A: How responsiv=
e
is the Multiple Sclerosis Impact Scale (MSIS-29)? A comparison with some
other self report scales. Journal of Neurology Neurosurgery and Psychiatr=
y
2006, 76:1539. Publisher Full Text
43 Mundt J, Marks I, Shear K, Greist J: The Work and Social Adjustment
Scale: a simple measure of impairment in functioning. British Journal of
Psychiatry 2002, 180:461-464. PubMed Abstract | Publisher Full Text
44 Curtis L, Netten A: Unit costs of health and social care. Canterbury:
PSSRU; 2006.
45 Stuifbergen A: Conceptualization and development of the Acceptance of
Chronic Health Conditions Scale. Issues in Mental Health Nursing 2008,
29:101-114. PubMed Abstract | Publisher Full Text
46 Sinclair VG, Wallston KA: The development and validation of the
Psychological Vulnerability Scale. Cognitive Therapy and Research 1999,
23:119-129. Publisher Full Text
47 Jopson NM, Moss-Morris R: The role of illness severity and illness
representations in adjusting to multiple sclerosis. Journal of
Psychosomatic Research 2003, 54:503-511. PubMed Abstract | Publisher Full
Text
48 Broadbent E, Petrie KJ, Main J, Weinman J: The Brief Illness Perceptio=
n
Questionnaire. Journal of Psychosomatic Research 2006, 60:631-637. PubMed
Abstract | Publisher Full Text
49 Power M, Champion LA, Aris SJ: The development of a measure of social
support: The Significant Others (SOS) Scale. Br J Clin Psychol 1988,
27:349-358. PubMed Abstract
50 Bowen J, Gibbons L, Gianas A, Kraft G: Self-administered Expanded
Disability Status Scale with functional system scores correlates well wit=
h
physician-administered test. Multiple Sclerosis 2001, 7:201-206. PubMed
Abstract | Publisher Full Text
51 Beecham J, Knapp M: Costing psychiatric interventions. In Measuring
mental health needs. Edited by: Thornicroft G. London: Gaskell; 2001.
52 Williams A: The role of the EuroQol instrument in QALY calculations.
University of York, Centre for Health Economics; 1995.
53 Boutron I, Moher D, Altman D, Schulz K, Ravaud P: Extending the CONSOR=
T
statement to randomized trials of nonpharmacologic treatment: Explanation
and Elaboration. Ann Intern Med 2008, 148:295-310. PubMed Abstract
54 Carpenter J, Kenward MG, White IR: Sensitivity analysis after multiple
imputation under missing at random: a weighting approach. Statistical
Methods in Medical Research 2007, 16:259-275. PubMed Abstract | Publisher
Full Text
55 Baron R, Kenny D': The moderator-mediator variable distinction in soci=
al
psychological research: conceptual, strategic and statistical
considerations. Journal of Personality and Social Psychology 1986,
51:1173-1182. PubMed Abstract | Publisher Full Text
56 Dunn G, Bentall R: Modelling treatment effect heterogeneity in
randomised controlled trials of complex interventions (psychological
treatments). Statistics in Medicine 2007, 26:4709-4745. Publisher Full Te=
xt
57 Emsley R, White I, Dunn G: Mediation and moderation of treatment effec=
ts
in randomised controlled trials of complex interventions. Statistical
Methods in Medical Reserach 2009, in press.
58 Williams P: The psychopathology of self-assessed health: a cognitive
approach to health anxiety and hypochondriasis. Cognitive Therapy and
Research 2004, 28:629-644. Publisher Full Text
59 Boyatzis RE: Transforming Qualitative Information. Thousand Oaks, CA:
Sage Publications; 1998.
60 Joffe H, Yardley L: Content and Thematic Analysis. In Research Methods
for Clinical and Health Psychology. Edited by: Marks D, Yardley L. London=
:
Sage; 2000.
61 Charmaz K: Constructing Grounded Theory: A Practical Guide Through
Qualitative Analysis. London: Sage; 2006.
62 Glaser BG, Strauss SA: Discovery of Grounded Theory. Strategies for
Qualitative Resarch. New York: Aldine; 1967.
Pre-publication history
The pre-publication history for this paper can be accessed here:
http://www.biomedcentral.com/1471-2377/9/45/prepub
[Ends]
Suzy Chapman
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