Telerehabilitation for persons with multiple sclerosis

  • Protocol
  • Intervention

Authors

  • Fary Khan,

    Corresponding author
    1. Royal Melbourne Hospital, Royal Park Campus, Department of Rehabilitation Medicine, Melbourne, Victoria, Australia
    2. Monash University, School of Public Health and Preventive Medicine, Melbourne, Victoria, Australia
    3. University of Melbourne, Department of Medicine, Dentistry & Health Sciences, Melbourne, Victoria, Australia
    Search for more papers by this author
  • Bhasker Amatya,

    1. Royal Melbourne Hospital, Royal Park Campus, Department of Rehabilitation Medicine, Melbourne, Victoria, Australia
    Search for more papers by this author
  • Jurg Kesselring

    1. Valens Hospital, Department of Neurology and Neurorehabilitation, Rehabilitation Center, Valens, Switzerland
    Search for more papers by this author

Abstract

This is the protocol for a review and there is no abstract. The objectives are as follows:

To investigate the effectiveness and safety of telerehabilitation intervention in pwMS for improved patient outcomes.

Specifically, we will aim to address the following questions:

  • Does telerehabilitation achieve better outcomes compared with traditional face-to-face intervention?

  • What types of telerehabilitation interventions are effective, in which setting and influence which specific outcomes (impairment, activity limitation and participation)?

Background

Description of the condition

Multiple sclerosis (MS) is a chronic neurological disease characterised by patchy inflammation, gliosis and demyelination within the central nervous system (CNS) that affects approximately 1.3 million persons worldwide (WHO 2008). Although considerable progress in pharmacological and non-pharmacological treatment of MS has occurred, it remains the third most common cause of neurological disability in adults aged 18 to 50 years (after trauma and arthritis) (Dombovy 1998). The global median estimated prevalence of MS is about 30 per 100,000 population (range 5 to 80), with a female preponderance (female to male ratio of 3:1) (Trisolini 2010; WHO 2008). The median estimated incidence of MS globally is 2.5 per 100,000 (with a range of 1.1 to 4) (WHO 2008).

The patterns of presentation in MS are heterogeneous and include: ‘relapsing remitting’ (RR) MS (85%), characterised by exacerbations and remission; ‘secondary progressive’ (SP) MS with progressive disability acquired between attacks (in 70% to 75% who start with RR, it is estimated > 50% will develop SPMS within 10 years; 90% within 25 years); ‘primary progressive’ (PP) MS (10%), where persons develop progressive disability from the onset; and ‘progressive relapsing’ (PR) MS (5%), where persons begin worsening gradually and subsequently start to experience discrete attacks (MS Australia 2012; Weinshenker 1989). The prognosis in MS is variable, hard to predict and depends on the type, severity and location of demyelinating lesions within the CNS (Hammond 2000; MS Australia 2012). Various factors such as older age at onset, progressive disease course, multiple onset symptoms, pyramidal or cerebellar symptoms and a short interval between onset and first relapse were significantly associated with worse prognosis in one study (Hammond 2000). Persons with MS (pwMS) have a prolonged median survival time from the time of diagnosis of approximately 40 years (Weinshenker 1989). Therefore, issues related to progressive disability (physical and cognitive), psychosocial adjustment and social re-integration progress over time. These have implications for pwMS, their carers, treating clinicians and society as a whole, in terms of healthcare access, provision of services and financial burden (Pfleger 2010; Trisolini 2010).

Persons with MS can present with various combinations of deficits such as physical (motor weakness, spasticity, sensory dysfunction, visual loss, ataxia), fatigue, pain (neurogenic, musculoskeletal and mixed patterns), incontinence (urinary urgency, frequency), cognitive (memory, attention), psychosocial, behavioural and environmental problems, which limit a person’s activity (function) and participation (Khan 2007). Cognitive and behavioural problems can be subtle and often precede physical disability requiring long-term care (Beer 2012; Weinshenker 1989). The care needs in this population are complex due to cumulative effects of the impairments and disabilities, the ‘wear and tear’ and the impact of aging with a disability. Longer-term multidisciplinary management is recommended, both in hospital and in community settings to maintain functional gains and social re-integration (participation) over time (Khan 2007; Khan 2010; WHO 2008). Despite recent advances in MS treatment and care, many pwMS are unable to access these developments due to limited mobility, fatigue and related issues, plus costs associated with travel. The emerging advances in information and communication technology (ICT) may represent an alternative efficient and cost-effective method to deliver rehabilitation treatment in a setting convenient to the patient, such as their home.

Description of the intervention

The terminology used in ICT in healthcare is often used interchangeably and includes: ‘telemedicine’, ‘telehealth’, ‘telehealthcare’, ‘e-Health’, ‘e-medicine’, ‘telerehabilitation’ etc. (Currell 2000; McLean 2010; McLean 2011; Winters 2002). In this review the term ‘telerehabilitation’ will be defined as ‘the use of information and communication technologies as a medium for the provision of rehabilitation services to sites or patients that are at a distance from the provider' (Rogante 2010; Theodoros 2008 ). The applications to date encompass systems ranging from low-bandwidth low-cost videophones to highly expensive, fully immersive virtual reality systems with haptic interfaces (Theodoros 2008).

Telerehabilitation extends rehabilitative care beyond the hospital process and facilitates multifaceted, often psychotherapeutic approaches to modern management of pwMS at home or in community (Huijgen 2008). It provides equal access to individuals who are geographically remote and to those who are physically and economically disadvantaged (Hailey 2011; Rogante 2010) and can improve the quality of rehabilitation delivered (Hailey 2011; Kairy 2009; McCue 2010; Rogante 2010; Steel 2011). It can give healthcare providers an opportunity to evaluate the intervention previously prescribed, monitor adverse events and identify areas in need of improvement. The treating therapists can monitor patients’ progress and optimise the timing, intensity and duration of therapy as required, which may not always be possible within the constraints of face-to-face treatment protocols in the current health systems (Hailey 2011; Steel 2011).

How the intervention might work

Telerehabilitation is an emerging method of delivering rehabilitation that uses technology to serve patients, clinicians and systems by minimising the barriers of distance, time and cost. The driving force behind this has been the need for an alternative to face-to-face intervention, enabling service delivery in the natural environment – that is in patients’ homes (Hailey 2011). This method of in vivo delivery of healthcare services can address associated issues of efficacy, problems of generalisation and increasing patient participation and satisfaction with treatment.

The benefits and advantages of telerehabilitation have been well documented (Bendixen 2009; Brennan 2009; Chumber 2012; Constantinescu 2010; Johansson 2011; Kairy 2009; Lai 2004; Legg 2004; Russell 2011; Steel 2011). A home-based physical telerehabilitation program was considered to be feasible and effective in improving function in pwMS (Finkelstein 2008). Telemedicine in pwMS as a tool has the potential for improved health care with reduction in care costs (Zissman 2012). A systematic review that analysed rehabilitation therapies delivered at home in stroke survivors showed positive outcomes, with a reduction in the risk of deterioration, improved ability to perform activities of daily living, reduced costs and duration of rehabilitation in a frail elderly population (Legg 2004). Other reports used telerehabilitation to direct multidisciplinary coordinated, goal-directed treatment to monitor clinical progress for patients at a distance (Hailey 2011; Kairy 2009; McCue 2010; Rogante 2010; Steel 2011). In these cases, telerehabilitation offered an opportunity to provide individualised rehabilitation intervention beyond the hospital setting, by regular monitoring and evaluation of the patients' needs and progress, with a range of services suited to the individual and their environment (Hailey 2011; Kairy 2009; McCue 2010; Rogante 2010; Steel 2011). Telerehabilitation also provides comparable health outcomes to traditional in-person patient encounters including improved patient satisfaction (Egner 2003; Finkelstein 2008; Hailey 2011; Huijgen 2008; Kairy 2009). It can encompass single or multiple interventions, or both, aimed at improving patient experience at the level of impairment, activity or participation, and can educate patients (and carers) in their ongoing self management.  

Why it is important to do this review

There is a strong evidence base to support the effectiveness of rehabilitation programs for pwMS (Khan 2007; Khan 2010). With increasing financial constraints on healthcare systems, alternative methods of service delivery in the community and over a longer term are now a priority. Telerehabilitation was found to be effective in  various neurological conditions including MS (Egner 2003; Finkelstein 2008; Huijgen 2008), stroke (Johansson 2011; Legg 2004), Parkinson’s disease (Giansanti 2008) and other non-neurological conditions such as musculoskeletal conditions (Russell 2011; Tousignant 2011), injuries (Bendixen 2008; Forducey 2003; Houlihan 2011) and chronic diseases (Steel 2011). However, there is as yet no systematic review of studies using telerehabilitation in pwMS to guide treating clinicians for evidence regarding its validity, reliability, effectiveness and efficiency in this population.

This review will analyse published (and unpublished) clinical trials relating to MS and telerehabilitation; identify the evidence base for its use; and discuss issues for future expansion of the evidence base by traditional research and other methods.

Objectives

To investigate the effectiveness and safety of telerehabilitation intervention in pwMS for improved patient outcomes.

Specifically, we will aim to address the following questions:

  • Does telerehabilitation achieve better outcomes compared with traditional face-to-face intervention?

  • What types of telerehabilitation interventions are effective, in which setting and influence which specific outcomes (impairment, activity limitation and participation)?

Methods

Criteria for considering studies for this review

Types of studies

We will include all randomised controlled trials (RCTs) and controlled clinical trials (CCTs), including quasi-randomised and quasi-experimental designs with comparative controls (where the method of allocation is known but is not considered strictly random).

Types of participants

We will include studies in pwMS (18 years and over) with a confirmed diagnosis of MS (Mc Donald 2001; Polman 2005; Poser 1993) and all  disease subgroups (relapsing remitting and progressive MS).

Types of interventions

We will consider all modalities (type, duration, frequency and intensity) of telerehabilitation intervention aimed at achieving patient-centred goals targeting improved patient outcomes in terms of enhancing function and participation. These may include: (a) individual (unidisciplinary) treatment modalities (e.g. psychological or physical interventions); and (b) multidisciplinary rehabilitation (i.e. delivered by two or more disciplines: occupational therapy, physiotherapy, exercise physiology, orthotics, other allied health and nursing, in conjunction with medical input).

The settings of telerehabilitation intervention may include the following:

  • outpatient or day treatment settings in community rehabilitation centres (rehabilitation health professional is not stationed);

  • home-based settings, in the patients' own homes and local community.

Control conditions may include the following:

  • no treatment;

  • placebo/sham;

  • any type of traditional face-to face rehabilitation treatment in outpatient or day treatment settings.

Studies will be excluded if they investigate acute medical/surgical/pharmacological interventions for pwMS provided via telemedicine technology in isolation, unless it is administered as concomitant intervention along with the telerehabilitation intervention, which is administered in the same way in both control and treatment group. Any studies exploring telerehabilitation technology for intra-professional communication (such as for second opinions) and for passive information provision, e.g. online education, where there is no direct interaction or involvement of a healthcare professional with the patient, will also be excluded.

Types of outcome measures

Diverse outcomes are expected, given the varied presentations of MS-related problems and goals of treatment related to MS severity. The specific outcome measures per se will not form part of the exclusion criteria for this review. All validated outcome measures used in studies will be reported.

Primary outcomes

Primary outcomes will reflect the level of activity limitation according to the International Classification of Health, Functioning (ICF; WHO 2001). These may include the following:

  • improvement in functional activity: such as activities of daily living (ADL), mobility, continence, and others;

  • improvement in symptoms or impairments, e.g. pain, spasm frequency, joint range of movement, involuntary movements; spasticity, etc.;

  • improvement in participation: e.g. quality of life, employment, education, social and vocational activities.

The measure of achievement of intended goals for treatment, e.g. goal attainment scaling or other measure of goal achievement will be included. This list is not exhaustive.

Secondary outcomes

These will include outcomes that reflect compliance with the intervention, service utilisation, and cost effectiveness of telerehabilitation (compared with traditional rehabilitation interventions).

Any adverse events that may have resulted from the intervention will be reported. Serious adverse effects will be defined as events that are life-threatening or require prolonged hospitalisation. Caregiver related issues, such as caregiver strain will be explored.

Timing of outcome measures
The time points for outcome assessments will be short-term (up to three months) and long-term (greater than three months) from the start of the intervention. Patient follow-up assessments will be considered similarly as short-term (up to three months) and long-term follow-up (greater than three months) after cessation of the intervention.

Search methods for identification of studies

See the 'Specialised register' section in the Multiple Sclerosis and Rare Diseases of the Central Nervous System Group module. We will consider articles in all languages with a view to translation, if necessary. We will extract trials coded with the specific key words and consider them for inclusion in the review.

Electronic searches

The authors, along with the Trials Search Co-ordinator from the Cochrane Multiple Sclerosis and Rare Diseases of the Central Nervous System Group, will search the Cochrane MS Group Trials Register and its sources: CENTRAL, MEDLINE, EMBASE, CINAHL, LILACS, PEDRO. The keywords are listed in Appendix 1.

In addition, we will search the clinical trials registries (http://clinicaltrials.gov) and the WHO International Clinical Trials Registry Platform (ICTRP) search portal (http://apps.who.int/trialsearch/Default.aspx) for all prospectively registered and ongoing trials.

Information on the Group's Trials Register and details of search strategies used to identify trials can be found in the 'Specialised Register' section within the Cochrane Multiple Sclerosis and Rare Diseases of the Central Nervous System Group's module.

Searching other resources

An expanded search will be performed to identify articles potentially missed through the database searches and articles from ‘grey literature' from 1996 to latest date. This will include the following:

  • handsearches of reference lists of all retrieved articles, texts and other reviews on the topic;

  • handsearches the most relevant journals related to MS and spasticity research and treatment (such as, but not limited to: Archives of Physical Medicine and Rehabilitation; Journal of Rehabilitation Medicine; Journal of Neurology; Journal of Neurology, Neurosurgery and Psychiatry, Clinical Rehabilitation, Neurology, Physical Therapy, Multiple Sclerosis and others);

  • searches using the related articles feature (via PubMed);

  • searches of ProQuest Dissertations and Theses;

  • searches of Web of Science for citation of key authors;

  • searches of SIGLE (System for Information on Grey Literature in Europe);

  • contacting local and foreign experts for further information (such as MS Groups/Associations, the Cochrane MS Group, key authors of publications in this review);

  • contacting authors and researchers active in this field.

We will also search the following websites for ongoing and unpublished trials:

Data collection and analysis

Selection of studies

Two reviewers (BA, FK) will independently screen and shortlist all abstracts and titles of studies identified by the search strategy for appropriateness based on the selection criteria. They will independently evaluate each study from the shortlist of potentially appropriate studies for inclusion or exclusion. If necessary, the full text of the article will be obtained for further assessment to determine if the trial meets the inclusion or exclusion criteria. If no consensus is met about the possible inclusion or exclusion of any individual study, a final consensus decision will be made by discussion amongst all the review authors. If there is still no consensus agreement regarding the inclusion or exclusion of a study, then we will submit the full article to the editorial board for arbitration. Authors will not be masked to the name(s) of the author(s), institution(s) or publication source at any level of the review.

We will seek further information about the method of randomisation or a complete description of the unidisciplinary and multidisciplinary rehabilitation interventions from the trialists, where necessary.

Data extraction and management

Two review authors (BA, FK) will independently extract data from each study that meets the inclusion criteria, using a standardised data collection form. A final check will be made by the third review author (JK). We will contact the primary authors of potentially eligible studies to provide data and clarification where adequate data are not reported. All studies that meet the inclusion criteria will be summarised in the 'Characteristics of included studies' table provided in Review Manager (RevMan) 5 software developed by The Cochrane Collaboration (RevMan 2012) and will include details on design, participants, interventions and outcomes.

The following information from individual studies will be reported:

  • publication details;

  • study design, study setting, inclusion and exclusion criteria, method of allocation, risk of bias;

  • patient population, e.g. age, type of MS, disease duration, disability (according to Kurtzke's Expanded Disability Status Scale (EDSS) score (Kurtzke 1982);

  • details of intervention;

  • outcome measures (primary and secondary);

  • withdrawals, compliance, length and method of follow-up and number of participants followed up.

Further details will be requested from the main author of the manuscript or studies, if data are missing. The results will be presented in a tabulated format in the ‘Summary of findings’ table.

Assessment of risk of bias in included studies

Two review authors (BA, JK) will independently assess the methodological quality of the included studies using the Cochrane 'Risk of bias' tool (Higgins 2011). We will assess the sequence generation, allocation concealment, blinding of participants, therapists and outcome assessors, incomplete outcome data and selective outcome reporting. A judgement of ‘yes’ will indicate a low risk of bias, ‘no’ will indicate a high risk of bias, and ‘unclear’ will indicate either unclear or unknown risk of bias. See Table 1.

Table 1. Levels of quality of individual studies
Judgement of risk of bias 
Risk of bias in all domains lowHigh methodological quality = ‘high-quality study’
Unclear or high risk of bias for one or more domainsLow methodological quality = ‘low-quality study’
High risk of bias for most domainsVery low methodological quality = ‘very low-quality study’

We will consider studies to be of high methodological quality if the risk of bias for all domains is low. We will term these studies 'high-quality studies'. We will rate studies as low methodological quality where there is unclear or high risk of bias for one or more domains and will term these as 'low-quality studies' (see Table 2). Any disagreements or lack of consensus will be resolved by a consensus between the authors. Appraisal will follow the risk of bias model created by The Cochrane Collaboration (Higgins 2011) and results will be presented using a ’risk of bias summary figure’.

Table 2. Levels of quality of a body of evidence in the GRADE approach  
Underlying methodologyQuality rating
Randomised trials or double-upgraded observational studiesHigh
Downgraded randomised trials or upgraded observational studiesModerate
Double-downgraded randomised trials or observational studiesLow
Triple-downgraded randomised trials or downgraded observational studies or case series/case reportsVery low

Measures of treatment effect

All data will be entered and analysed in RevMan (RevMan 2012). We will calculate for each outcome of interest summary estimates of treatment effect (with 95% confidence interval (CI)) for each comparison. Where possible, we will calculate risk ratios (RR) with 95% CIs for dichotomous data and differences in means or standardised differences in means (SMD) with 95% CIs for continuous data. We will decide whether or not to perform meta-analyses based on the similarity of reported data of the included trials; if clinical heterogeneity is present, we will perform a qualitative review. We will perform statistical pooling only if the studies are similar enough with regards to clinical features and treatment. We will discuss and present the results of individual studies in tabular and graphical format, where data aggregation is not possible.

Unit of analysis issues

The anticipated appropriate unit of analysis will be the level at which randomisation occurred (e.g. parallel group design, cluster randomised trials, cross-over trials, etc.), type, duration, intensity and setting of telerehabilitation intervention.

Dealing with missing data

If data in the potentially eligible studies are insufficient or missing, we will contact the primary authors to obtain additional information and clarification by personal communication in the form of a letter, email or telephone call. If the data remain unavailable or insufficient to the extent that the study cannot be included in the meta-analysis and attempts to obtain data have been exhausted, we will report the study results in the review and discuss the results in the context of the findings. In addition, studies with fatal flaws (for instance, withdrawals by more than 40% of the patients, nearly total non-adherence to the protocol, or very poor or non-adjusted comparability in the baseline criteria (van Tulder 1997)) will be excluded.

Assessment of heterogeneity

We will conduct statistical analysis as described in the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2011). Clinical heterogeneity will be assessed by examining the characteristics of studies, the similarity between the types of participants, settings, interventions (frequency, intensity, duration) and outcomes, as specified in the 'Criteria for considering studies for this review' section. To check for statistical heterogeneity between studies, we will use both the I² statistic and the Chi² test of heterogeneity as well as visual inspection of the forest plots.

We will consider the presence of substantial heterogeneity to be indicated by an I² > 50%. We will use a fixed-effect meta-analysis if the I² ≤ 50% and if the I² > 50% we will explore the individual trial characteristics to identify potential sources of heterogeneity, using pre-planned subgroup analyses. We will perform meta-analysis using both fixed-effect and random-effects modelling where there is substantial heterogeneity to assess sensitivity to the choice of modelling approach. We will report the most conservative outcome, if we find non-identical results.

Assessment of reporting biases

A comprehensive search strategy, which includes searching for unpublished studies (grey literature), and searching trials registers (See 'Search methods for identification of studies') will be used to avoid reporting biases. Publication bias will be investigated using funnel plots (Egger 1998) and all unpublished studies will be appraised in a comprehensive method before considering for inclusion in the review.  We will contact the authors for the full data or the reason for not publishing the data, where data are not reported or published in full.

Data synthesis

Two independent review authors (BA, FK) will extract data from the included trials. Any disagreements will be resolved by the third author (JK) and through discussion, with reference to the original report. An intention-to-treat analysis will be used where possible and RevMan (RevMan 2012) will be used for all analyses. We will pool results from clinically similar studies for meta-analysis if sufficient studies are available. A quantitative analysis will be attempted if there is clinical homogeneity, and the methods and available data in each study allow it.

If appropriate, we will calculate a weighted treatment effect across trials using RevMan. We will initially use a fixed-effect model using the Mantel-Haenszel method for dichotomous (or binary) data (e.g. clinical improvement or no clinical improvement) and report the results as risk ratios (RRs) with 95% confidence intervals (CIs) and risk differences (RDs) with 95% CIs. For continuous data (e.g. range of motion) we will calculate the treatment effect using SMD and 95% CI where different scales were used for the assessment of the same outcome, and using MD and 95% CI where studies have all used the same method of measuring outcome. We will use the inverse variance method for combining mean differences (MDs) or SMDs for continuous outcomes. Statistical pooling will be performed only if the studies are similar enough with regard to clinical features. Based on the similarity of the included trials, we will decide whether or not to perform meta-analyses  A qualitative review will be performed if clinical heterogeneity is present,  

The GRADE approach will be used for quality of evidence, as described in Chapter 12 of the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2011). We will analyse the methodological quality of RCTs and CCTs using the GRADE system for existing evidence (Higgins 2011). The GRADE approach is applicable to all types of studies. The three levels of quality using the GRADE approach and the four levels of grading the body of evidence of included studies are shown in Table 1 and Table 2.

Subgroup analysis and investigation of heterogeneity

We will perform subgroup analysis for the following subgroups if data are available.

  1. Type of telerehabilitation intervention (unidisciplinary or multidisciplinary, or both).

  2. Type of MS (relapsing remitting, progressive) and severity (i.e. EDSS < 6; > 6), duration of follow-up of participants (≤ 3 months; > 3 months).

Factors will be evaluated if there is significant heterogeneity and include: types of participants, the setting, frequency, duration and intensity of telerehabilitation intervention.

Sensitivity analysis

We will conduct sensitivity analyses by either excluding trials of low methodological quality or CCTs. We will consider and discuss the results of these analyses in comparison to the overall findings. Many issues suitable for sensitivity analysis may only be identified during the review process. We will also conduct any required sensitivity analysis as described in the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2011).

Acknowledgements

We thank the Editorial Board of the Cochrane Multiple Sclerosis and Rare Diseases of the Central Nervous System Review Group for their support and assistance. We would also like to thank Dr. Graziella Filippini and Dr. Paola Masconi for reviewing the protocol.

Appendices

Appendix 1. Keywords

{telecommunications*} OR {telemedicine} OR {telehealth} OR {telehealthcare} OR {e-health} OR {e-medicine} OR {mobile health} OR {information technology} OR {information communication technology} OR {internet} OR {web-based} OR {computer}

Contributions of authors

Fary Khan (FA), Bhasker Amatya (BA) and Jurg Kesselring (JK) were involved in all aspects of the protocol.

Declarations of interest

The authors are clinicians in the field of Physical and Medical Rehabilitation who wish to provide the best possible service to their patients. None have personal or financial conflicts of interest in the findings of this review.

Sources of support

Internal sources

  • Department of Rehabilitation Medicine, Royal Melbourne Hospital, Australia.

External sources

  • None, Not specified.

Ancillary