Methods

4 publications

One centre cross‐over trial: open randomised fast‐track phase II controlled trial

Randomisation ratio 1:1, stratified by gender, age, date of diagnosis and communication capacity

N = 52 / Available for analysis = 46

Treatment duration: 12 weeks

Follow‐up duration: 24 weeks

Participants

Inclusion criteria:

• Diagnosis of MS

• Living in South East London

• Having possible palliative care needs (score > 8.0 on Expanded Disability Status Scale ‐ EDSS)

• Patients presenting problems with: symptom control, psychosocial needs, difficulty with hydration or nutrition, planning directives

Exclusion criteria:

• Patients deemed as having urgent needs because of rapid deterioration

• Severe symptoms

Interventions

Intervention: Palliative Care Team ‐ Fast track

• Multidisciplinary team (coordinator, nurse, specialist palliative medicine and psychosocial worker)

• Visits at home or where the patient was located

• Managing symptoms, providing social support, advising other professionals related to the case, establishing advance directives

• Patients received 3 visits in 12 weeks.

Control: Standard Best Practice

• Waiting list

• Received standard care for MS patients: MS nurse specialist, district nurses, social services, general practitioners, hospital neurology service, continence advice, psychiatrist, psychologist, home physiotherapy and rehabilitation services available

• After 12 weeks, patients were asked if they wanted to receive the palliative care intervention.

Outcomes

Primary outcome:

• Palliative Care Outcome Scale ‐ MS Symptom Scale (POS‐S‐MS): self‐assessment of potential MS symptoms from 0 (no problem) to 4 (overwhelming problem). Evaluated MS‐specific symptoms, pain, nausea, vomiting, mouth problems, sleeping difficulty, anxiety, concerns and practical needs.

Secondary outcomes:

• Self‐reported quality of life: Multiple Sclerosis Impact Scale (MSIS). Higher scores mean worse symptoms.

• Impact of MS: Multiple Sclerosis Impact Scale (MSIS). Higher scores mean worse symptoms.

• Zarit (caregiver) Burden Interview (ZBI): 12‐item version. Higher scores mean higher burden.

• Modified Lawton positivity questionnaire (from Lawton Instrumental Activities of Daily Living Scale (IADL)). Higher scores mean high function.

• Costs (formal and informal)

Time points: baseline, six weeks from baseline, twelve weeks from baseline, eighteen weeks from baseline, twenty‐four weeks from baseline

Notes

Contact made with authors. Dr Nilay Hepgul, on behalf of Dr Irene Higginson and Dr Polly Edmonds, provided requested data.

Patient consent: obtained

Recruitment: from August 2004 to August 2005

Ethics approval: King's College Hospital NHS Trust Local Research Ethics Committee (Protocol number: 01‐04‐018)

Funding: MS Society 676/01

Authors declared no competing interests.

MRC Framework for the Evaluation of Complex Interventions

Detailed protocol registered at clinicaltrials.gov: NCT00364936 (https://clinicaltrials.gov/ct2/show/NCT00364936?term=NCT00364936&rank=1)

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Quote: "Randomization was conducted by independent statistical colleagues using the minimization method immediately after baseline interview."

The sequence generation was not specified.

Allocation concealment (selection bias)

Unclear risk

Quote:"Statistical colleagues, independent of the research and clinical team, registered the patients, conducted the randomisation and informed the research team, who then informed the patients, and if patients were "fast track" passed their details to the clinical team."

The allocation concealment was not specified.

Blinding of participants and personnel (performance bias)
Subjective

High risk

Given the nature of the intervention, there was no blinding of participants and personnel.

Blinding of outcome assessment (detection bias)
Subjective

High risk

Quote: "We were unable to blind the interviewers...."

Unblinded outcome assessor

Incomplete outcome data (attrition bias)
Subjective

High risk

Data missing in MSIS physical subscale at 3 months for 10/26 (38%) participants in the fast‐track group and 19/26 (73%) participants in the control group

Selective reporting (reporting bias)

Unclear risk

The study protocol was registered retrospectively in August 2006 (enrolment started in March 2004). Available from: https://clinicaltrials.gov/ct2/show/NCT00364936?term=NCT00364936&rank=1). As the protocol was retrospectively registered, we were not able to assess if all planned outcomes were reported.

Other bias

Low risk

There was no imbalance at baseline. The authors reported results on the first and the second period.

Methods

2 publications

Monocentric, phase II, pilot randomised controlled trial

Parallel design

No sample size was calculated.

Randomisation ratio 1:1, stratified by same diagnosis (ALS, MS or PD) and similar clinical necessities

MS patients = 18 / Available for analysis = 16

Intervention group = 10 / Control group = 8

Treatment duration: 16 weeks

Follow‐up duration: 16 weeks

Participants

Inclusion criteria:

• Patients living in Turin

• Severity of MS defined by the Expanded Disability Status Scale (EDSS > or = 8.5)

Exclusion criteria:

• Cognitive state compromised and the patient could not complete the outcome measures

Interventions

Intervention: Specialist Palliative Care Service ‐ Fast track

• FARO Foundation (Fondazione Assistenza e Ricerca Oncologia)

• Team trained and specialised in palliative care: physician, nurse, psychologist and physiotherapist

• Assessed symptoms, prescribed medications, provided nursing care, physical therapies, psychological support, bereavement care

• 16 weeks: weekly visits from a team member and team discussion of patients every two weeks

• Palliative treatment based on patients needs assessed at the first visit

Control: (Standard treatment)

• Waiting list of 16 weeks

• Received standard care provided by primary medicine and hospital

Outcomes

Primary outcomes:

• Patients individual Quality of Life measured with Schedule for the Evaluation of Individual Quality of Life Direct Weight (SEIQoL‐DW). Higher scores mean better quality of life.

• Family informal caregiver burden of care measured with Caregiver Burden Inventory (CBI). Lower scores mean lower burden of care.

Secondary outcomes:

• Physical symptoms measured with Numerical Rating Scales (NRS 0‐10): pain, shortness of breath, quality of sleep, urinary problems, intestinal problems, oral symptoms. Lower scores mean lower symptoms.

• Psychological symptoms measured with Hospital Anxiety and Depression scale (HADS): anxiety, depression. Higher scores mean higher distress.

• Social issues measured with Numerical Rating Scales (NRS 0‐10): social isolation and service satisfaction. Higher scores mean lower sense of isolation.

• Spiritual issues measured with Numerical Rating Scales (NRS 0‐10): meaning of the experience and help from faith. Higher scores mean higher meaning.

• Disability measured with Activity of Daily Living (ADL), Instrumental Activity of Daily Living (IADL), Amyotrophic Lateral Sclerosis Functional Rating Scale‐Revised (ALSFRS‐R) for patients with ALS, Expanded Disability Status Scale (EDSS) for patients with MS, Hoehn & Yahr (H&Y) for patients with PD: activity daily living, cognitive status and specific disability scales

Time points: baseline, 16 weeks from baseline

Notes

Contact made with authors. Simone Veronese provided all available data.

Design followed the Medical Research Council Framework.

No protocol was registered.

Competing interests: none declared

Patient consent: obtained

Ethical approval: Ethics Committee of Department of Neuroscience, University of Torino and S. Luigi Gonzaga Hospital, Orbassano and University of Kent Ethics Committee, University of Kent at Canterbury, UK

Funding: no funding declared

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

High risk

Quote: "The randomisation was undertaken by placing two unrecognisable white folders, containing the two patients charts, on a secretary' s desk. The secretary was asked to pick up one randomly and this was chosen as the Fast Track patient, the other patient went into the Standard Treatment group."

The method for randomisation was inadequate.

Allocation concealment (selection bias)

High risk

Allocation concealment was not done.

Blinding of participants and personnel (performance bias)
Subjective

High risk

Quote: "Team members and study personnel could not be blind to participants, as they were involved in care."

Given the nature of the intervention, there was no blinding of participants and personnel.

Blinding of outcome assessment (detection bias)
Subjective

High risk

Quotes: "The team can assess symptoms, prescribe medications, provide nursing care and physical therapies as well as psychological support and bereavement care."

The same team that provided care also assessed the outcomes.

Incomplete outcome data (attrition bias)
Subjective

High risk

Data provided by the authors (email): 2/10 (20%) losses for palliative care group and no loss for control group

Selective reporting (reporting bias)

Unclear risk

No protocol was found to compare planned and reported outcomes.

Other bias

Low risk

There was no imbalance at baseline. No other source of bias was found.

Methods

4 publications

Multicentric phase II/III single‐blind randomised controlled trial and nested qualitative study

Three Italian centres: Milan, Rome and Catania

Dyad: patient and caregiver

Randomisation ratio 2:1, stratified for EDSS score (8.0‐8.5, 9.0‐9.5), cognitive status and centre

N = 78 / Available for analysis = 76

Treatment duration: 6 months

Follow‐up duration: 6 months

Participants

Inclusion criteria:

• Definite MS

• 18 years or older

• Primary or secondary progressive MS course

• Expanded Disability Status Scale (EDSS) > or = 8.0

• Two or more unmet care needs: symptoms management, personal care and hygiene, activities of daily living, outdoor mobility and transport, relationships and communication, leisure and holidays, psychological well‐being and social role, information, access to services, co‐ordination of services, competent professionals

• One or more of the following patient clinical indicators: significant complex symptoms and medical complications; dysphagia and poor nutritional status; communication difficulties; cognitive impairment, notably the onset of dementia

• Presence of a caregiver: family member, relative or friend, who is next or is the decision maker as designated by the patient and with whom the patient shares his/her life

• Signed informed consent

Exclusion criteria:

• Hospitalised/institutionalised patients

• Already receiving palliative care

• Living out of the study areas

Interventions

Intervention: HPA (Home‐based palliative approach)

• Palliative care team: nurse (team leader), physician, psychologist, and social worker

• All team members were trained in the HPA intervention.

• First 3 months: team home visits every two weeks

• Last 3 months: team home visits when necessary

• At first visit, the team makes a comprehensive assessment of the dyad.

• The treatment plan is agreed on, discussed with the caring physician, and activated by involvement of pertinent services available in the area.

• If any emergency occurred, dyads contacted the carrying physician or the emergency services.

Control: usual care (UC)

• Health and social services of the Italian National Health Service

• Patients receive the three blind examiner visits and the monthly telephone interviews.

At the end of the study, control group dyads were offered the home palliative care program.

Outcomes

Primary outcomes:

• Quality of Life measured with Schedule for the Evaluation of Individual Quality of Life ‐ Direct Weighting (SEIQoL‐DW). Higher scores mean better quality of life.

• Symptom burden measured with Palliative care Outcome Scale ‐ Symptoms ‐ MS (POS‐S‐MS): self‐assessment of potential MS symptoms from 0 (no problem) to 4 (overwhelming problem). Evaluated MS‐specific symptoms, pain, nausea, vomiting, mouth problems, sleeping difficulty, anxiety, concerns and practical needs.

Secondary outcomes:

• Emotional, psychological and spiritual needs measured with Palliative Outcome Scale (POS): measured patients' physical symptoms, psychological, emotional and spiritual, and information and support needs. Lower scores mean lower symptoms.

• Function measured with Functional Independence Measure (FIM): assessed the functional status and if the patient was able to perform daily living activities. Higher scores mean the patient is more independent.

• Anxiety and depression measured with Hospital Anxiety and Depression (HADS): 7 items assessed anxiety and 7 items assessed depression symptoms. Higher scores mean worse symptoms.

• Carer‐related quality of life measured with Medical Outcomes Study 36 – Item Short–Form Health Survey (SF‐36). Higher scores mean better health‐related quality of life.

• Carer‐related anxiety and depression measured with Hospital Anxiety and Depression (HADS): 7 items assessed anxiety and 7 items assessed depression symptoms. Higher scores mean worse symptoms.

• Carer‐related quality of life measured with European Quality of Life Five Dimensions (EQ‐5D‐3L). Lower scores mean worse quality of life.

• Caregiver burden measured with Zarit Burden Interview (ZBI): 22 items assessed caregiver burden related to patients' disability. Higher scores mean greater burden.

• Safety (emergency ward visits, hospitalisations, death)

Time points: baseline, three months from baseline and six months from baseline

Notes

To date, authors have not answered our contact for requesting data.

All randomised participants were included in the ITT analysis for the primary outcomes.

Protocol registered at WHO‐ICTRP: http://apps.who.int/trialsearch/Trial2.aspx?TrialID=ISRCTN73082124

Study in accordance with the Declaration of Helsinki

Recruitment: from January 2015 to November 2015

Patient consent: obtained

Ethical approval: Foundation IRCCS Neurological Institute 'C. Besta' Milan, Foundation 'S. Lucia' Hospital Roma and University Hospital Catania

Funding source: the Fondazione Italiana Sclerosi Multipla (FISM) funded the trial (Grant No. 2014/S/1 to A.S.).

All authors declared no competing interest, although some of them received speaker honoraria, research funding, speaking fees or travel grants from different companies (Bayer Schering, Biogen Idec, Novartis, Genzyme, Merck Serono, Sanofi Aventis).

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Quote: "Allocation to treatment groups was done using a third‐party, web‐based computerized randomisation procedure with stratified minimization for EDSS score (8.0‐8.5, 9.0‐9.5), presence of severe cognitive compromise (clinical judgement), and centre."

The method for randomisation was adequate (web‐based computerised randomisation).

Allocation concealment (selection bias)

Low risk

Quote: "Following randomisation, an email informing on dyad assignment is sent to the Principal Investigator and the HPA team."

The method for allocation concealment was adequate.

Blinding of participants and personnel (performance bias)
Subjective

High risk

Quote: "The team informs the dyad about assignment. The team also contacts the patient's caring physician (GP, neurologist or other physician responsible for the patient's care) to inform him/her about the study and (for dyads assigned to HPA) define a common agenda."

Given the nature of the intervention, participants and personnel could not be blinded.

Blinding of outcome assessment (detection bias)
Subjective

Low risk

Quotes: "To reduce measurement bias, the baseline and follow‐up assessments are performed by independent examiners blind to treatment assignment (one examiner plus backup at each centre, both trained, neither involved in HPA delivery). Prior to each follow‐up visit, study dyads will be reminded not to disclose their allocation by mentioning any contact with the HPA team to the blind examiner."

"The blind examiners used a web‐based case report form (eCRF), so that visit 1‐3 data were available to HPA teams and coordination unit."

The outcome assessors were blind to participants allocation and participants were oriented not to mention their group allocation to the assessors.

Incomplete outcome data (attrition bias)
Subjective

High risk

The authors reported results of ITT analysis using an imputation method for the SEIQOL‐DW (lost participants 11/52, 21% in the HPA group and 5/26, 19% in the UC group).

Selective reporting (reporting bias)

Low risk

Prospective protocol available at http://isrctn.com/ISRCTN73082124. All planned outcomes were properly reported.

Other bias

Low risk

There was no imbalance at baseline. No other source of bias was found.