Overview
In this chapter, the exploratory findings relating to the patterns and predictors of language, optimal SLT interventions and potential tailoring of SLT for subgroups of people with aphasia after stroke are summarised. We then consider the strengths and limitations of these findings, before describing the study’s patient and public involvement (PPI), the clinical and research implications, and the conclusions.
Summary of findings
Patterns of language recovery
We explored the patterns of language recovery among participants who had access to SLT (in the context of the primary research). We looked at when recovery occurred and in what language domain. We had insufficient data to consider whether or not the patterns of language recovery varied by different languages spoken.
Participants allocated to receive SLT demonstrated higher language scores over the study duration across all language domains, with modest gains observed on measures of other spoken language, reading comprehension and writing. Data for participants who had only historical SLT were limited, as many were permitted SLT access after the comparison group completed the SLT intervention period and prior to follow-up data collection points (see Table 11).
We had insufficient data from a pure natural history population (participants who, we could be reasonably confident, had no access to SLT after stroke) to plot language recovery by language domain. With the benefits of SLT for aphasia well established, it is ethically unlikely that such data will be available in the future, unless gathered in an international context in which SLT for aphasia is not part of usual care; however, in such contexts, other aspects of stroke care are also likely to differ.
When considering participant data at study entry time points only, time since stroke was inversely associated with the severity of language impairment across all language domains, suggesting spontaneous improvement or selection bias in data sets recruiting at later time points following stroke. Absolute proportion of change in participants’ language abilities over time was greatest on measures of functional communication, overall language ability and auditory comprehension.
Predictors of recovery
We explored the predictors of language recovery outcomes following aphasia by individual characteristics (age, education, cognition, monolingual or multilingual), rehabilitation environment (social support, socioeconomic demographics, ethnicity), stroke profile (severity, lesion type, size, location) and by language domain (overall language ability, auditory comprehension, spoken language, reading comprehension and writing). We were unable to take some analyses forward because of insufficient data (the role of monolingualism or multilingualism, ethnicity, cognition) or because the format of available data prevented meaningful synthesis (education, socioeconomic demographics). Lesion type and size are currently being investigated by a collaborating research group (e.g. PLORAS119); to avoid research waste, these were not taken forward in this study.
Across all language domains, when a significant change from baseline was evident, the greatest change in language performance from baseline was among participants enrolled within 1 month of stroke. Change in language performance scores from baseline appeared to lessen with increasing time from stroke to study enrolment.
Using regression, we examined the proportion of recovery within each language domain and found that increasing time from stroke to study entry was significantly associated with poorer recovery on all language domains. Increasing age was significantly associated with poorer recovery on overall language ability. Sex was also included owing to its known relationship with other stroke outcomes (see Table 7). Each of these covariates contributed to base models in subsequent analyses (see Table 11).
Optimum speech and language therapy interventions for aphasia after stroke
Using a one-stage network meta-analysis with direct and indirect comparisons, we explored language recovery in the context of SLT aphasia rehabilitation intervention regimen (timing, frequency, duration, intensity, dosage, home-based therapy), approach (theoretical approach and impairment target) and delivery model (functional relevance, one to one or group).
Controlling for age, time since stroke and sex, we found that SLT frequency, duration, intensity and dosage were significantly and selectively associated with language outcomes. Auditory comprehension gains were associated with the frequency, intensity, dosage (including home practice) and tailoring of SLT. Naming gains were associated with the frequency and dosage of SLT. Functional communication gains were associated with dosage (see Report Supplementary Materials 5–17).
We considered language gains made from baseline, and found that SLT regimen was associated with language recovery and varied by domain. Overall language ability and functional communication scores improved most in the context of receiving SLT for up to 2 hours weekly, delivered daily (> 4–5 days weekly). Auditory comprehension gains were greatest alongside SLT in excess of 9 hours weekly, over 3–4 days. The best overall language gains were associated with 20–50 hours of SLT. The greatest overall language and functional communication gains were seen in the context of mixed SLT approaches, whereas SLT aimed at improving word-finding was associated with the greatest gains in auditory comprehension. Language recovery on these measures was greatest in the context of SLT tailored by functional relevance to the participant and when home practice was prescribed. We found no indication that the expertise of the SLT provider, the mode of therapy (face to face, group or computer-based), the context of SLT delivery or the theoretical approach were related to participants’ language change from baseline, although naming, duration and the theoretical approach findings were based on a limited data set (see Table 11).
Speech and language therapy interventions: age, time since stroke, severity and sex subgroups
Subgroups were defined by individual (age, sex), stroke (time since onset) and aphasia characteristics (severity at baseline). The association between language scores and SLT intervention components was examined using a network meta-analysis approach. Participant numbers were low and the findings were treated with caution.
Language recovery was best for both younger and older participants in the context of 20–50 hours of SLT over several SLT days weekly. For both groups, auditory comprehension improved most when associated with highly intensive SLT (> 9 hours weekly). The best language gains for the older group on other domains occurred alongside less intensive approaches (up to 2 hours of SLT weekly).
When significant changes from baseline were observed, participants within 3 months of aphasia onset made most language gains in the context of 20–50 hours of SLT, delivered two to four times weekly for up to 2 hours each week. In contrast, participants starting SLT > 3 months after stroke made their best gains alongside SLT in excess of 50 hours in total, delivered four to five times weekly, for 3–4 hours weekly. The only variation to this profile was that, regardless of time since onset, both groups made their best gains in auditory comprehension with > 9 hours of SLT weekly.
Language gains from baseline were greater for participants with moderate–severe aphasia than for those with a milder aphasia across language domains. People with milder aphasia, already scoring highly on assessments, may have had less scope to demonstrate improvement on assessment tools unable to capture language change at or close to the highest possible score (the ceiling effect). The moderate–severe group’s best language gains were associated with frequent SLT (three to five times weekly), for between 2 and 4 hours weekly, and a total dosage of 14–50 hours, or more, depending on the language outcome.
Language gains across all domains were higher for females than for males. Females’ highest language gains occurred with up to 2 hours of SLT weekly, delivered over 2–4 days. Males’ highest language gains occurred with intensive, daily SLT (3–4, or even > 9, hours weekly, depending on language modality). Males’ and females’ best overall language gains were associated with 20–50 hours of SLT, although higher SLT dosage (> 50 hours) was associated with the highest auditory comprehension gains for female participants and the highest functional communication gains for male participants.
Strengths
Diversity of data set
This international collaboration of multidisciplinary researchers created one of the largest IPD data sets on 5928 people with aphasia and on language after stroke, gathered across 174 clinical or research settings, incorporating pre-existing databases, RCTs, non-RCT designs and clinical registries. The diversity of data sets, languages, severities and contexts (clinical and research) supports generalisation of the results. The primary research data sets met all the eligibility criteria and were further filtered for each research question. The database was sparse, with each data set typically including just some of the variables relevant to the analysis. Thus, the high number of data sets included in the database was essential to ensure sufficient overlap in the availability of variables to support the planned analysis. In addition, we required enough data sets to ensure an adequate sample size to explore the characteristic diversity of this population group, a wide range of language outcomes and the complexity of SLT interventions for aphasia.
Quality of data set
The database included RCTs generally graded as being at a low risk of bias (random sequence generation, concealment of allocation, blinding and few with unexplained attrition). For non-RCT data sets, the lack of randomisation was a risk of bias. Blinding of outcome assessors and the comparability of the groups at baseline were reassuring. The analyses based on IPD derived from RCTs were typically similar to the analyses that included the non-RCT IPD data sets.
We included unpublished IPD and eligible data sets identified by the systematic review. Responses to invitations to contribute data sets and inclusion of extensive IPD from the public domain (including complete RCT data sets) contributed to a reduction in the risk of publication bias. The formal assessment of publication and historical bias found no evidence to suggest that the findings were influenced by such biases.
Data relevant to the analyses were carefully identified, extracted and subsequently checked by a second researcher and (when possible) the contributing primary researchers. Data were additionally checked by reviewing plots and distributions, network graphs and through constant reference to the primary research data set to ensure accuracy. We standardised language recovery outcome by language domain across data sets and categorisation of SLT interventions by impairment target and theoretical approach through consensus with collaborators.
Language data
The language data reflect participants’ performance across several language modalities, gathered using specialised language measurement tools rather than a brief language item on a stroke scale.29 Only published language measures were included. Screening tool data were excluded.97 We preserved a clinically relevant language measurement reference, transforming the data to a single anchor measure for each outcome. Thus, measures of language change could be interpreted in the context of a clinically relevant scale as used in aphasia rehabilitation. The international multilingual collaboration supported data extraction and analysis of non-English aphasia assessment tools.
Speech and language therapy data
Working across an international, multilingual context supported the SLT data extraction, analysis and interpretation. Classification of SLT approaches by treatment target and theoretical approach was undertaken by the collaboration, and, following consensus review and approval (with minor edits), was sustained throughout the project. The aphasia intervention classification framework is an important adjunct to the TIDieR checklist to encourage transparency of reporting in SLT intervention studies for aphasia after stroke.86
Individual participant data one-stage approach to meta-analysis
Findings from IPD and group summary meta-analysis can be equivalent, but the IPD data synthesis approach allowed inclusion of different data in existing meta-analyses. We included unpublished, clinical data sets, IPD, outcomes and extended follow-up time points excluded from aggregated published reports addressing some of the risks of outcome reporting bias. Using participants as the unit of analysis, we also had more power to identify clinically relevant interactions, which can be more easily interpreted to specific clinical populations than data derived from aggregate data alone. Study variability was monitored; only findings for which study variability was low to modest were reported, and these variations were highlighted to the reader. The multiple analyses were presented in a balanced manner, with all non-significant findings available for reference.
Limitations
Exploratory approach
We adopted an exploratory approach to the analysis, and results should be interpreted in this context. The ambition was to inform prioritisation, design, delivery and reporting of definitive research to confirm (or refute) these findings. It was impossible to anticipate the completeness of the final database. Network diagrams accompanied each comparison by language domain and every effort was made to ensure well-constructed networks. When it was not possible to make comparisons between all interventions, this was reported as an unreliable analysis. There were few direct comparisons or, when available, comparison was limited to one or two data sets. Network graphs were reasonably balanced, but only because of the sparsity of direct comparisons between each node. The availability of data and the network geometry highlighted comparisons that were unavailable; these evidence gaps should be addressed as a priority in future RCTs.
Diversity of data set
This database demonstrated a marked imbalance towards English-language data (more than half the data set), with other languages often represented by a single data set. We applied no language restrictions to the searching or inclusion criteria. The imbalance in language representation is reflective of the wider aphasia research literature. Recovery from aphasia in monolingual and bilingual stroke survivors may differ. Languages vary from each other in grammatical structure (e.g. English grammar, compared with agglutinating languages such as Finnish) and writing systems (Latin alphabetic, e.g. English, vs. Greek alphabet or Chinese logographic scripts). Non-English aphasia research has historically been hampered by the lack of rigorous, valid and reliable aphasia assessments, although some co-ordinated initiatives are under way that aim to change this landscape.120
Reading comprehension and writing interventions and outcomes were also limited in their representation in the database, hindering the insight into impact on and recovery of these language domains.
Data collection limitations
Demographic, language and SLT intervention data, although sufficient for the purposes of the primary research activities, were often limited in their contribution to the secondary data analyses. For example, the analysis was often limited by a lack of outcome data captured at both baseline and follow-up time points. Historical SLT groups were rarely measured following the comparator intervention period. Participants allocated to receive SLT in the primary research had limited post-intervention follow-up, thereby limiting our insight into long-term maintenance of language recovery gains.
We also undertook a comprehensive literature search and systematically invited contributions and included IPD from the public domain to ensure that the breadth of included data sets would compensate for the anticipated sparsity of the data. Data extraction of IPD in the public domain was, as expected, often limited to baseline data, but also included four complete RCT IPD data sets. It was not possible to include all datasets identified as potentially eligible. In many cases we had no response to our inviation, while in others the IPD was no longer available.
Descriptions of speech and language therapy interventions
Speech and language therapy intervention descriptions typically lacked information on tailoring, adherence and home practice tasks. SLT intervention descriptions were rarely available at IPD level, and SLT intervention data were insufficient to support all the planned analyses, in some cases resulting in a network meta-analysis with too few connections to permit complete direct and indirect comparisons. For other networks, we used a reference group to close the analysis loop and strengthen the analysis, but some orphan groups were still evident (see Appendices 11–14). These networks gaps should be addressed in targeted RCT-based comparisons. Other SLT interventions are reported in the wider literature, but these were not represented in this database because of unavailability or issues with eligibility.
Language outcome limitations
We sought to adopt the ICF framework in the RELEASE study to describe the impact of aphasia and rehabilitation interventions. Language impairment was well represented across several language domains. Measures of communication participation or activity items, however, were typically represented by isolated data sets and available data items could not be meaningfully synthesised. The development of new assessments that capture such constructs121 and recent consensus on a core outcome set for aphasia research122 are important steps to ensuring that future aphasia research will reflect outcomes of importance to people with aphasia, their families and health-care professionals.122
Stroke description limitations
The description of stroke (and related health data) was limited in the included aphasia data sets. Stroke severity and acute care stroke interventions, such as thrombolysis, are important rehabilitation and recovery factors.29,123 Comorbidities and stroke risk factors are relevant to aphasia recovery29 and stroke rehabilitation.124 Standardisation of data collection on these items across all stroke and aphasia recovery research would support further clarity on their relevance to aphasia recovery.125,126
Inclusion limitations
The planned analysis focused on specific language outcomes to ensure feasibility; however, we acknowledge that many other important questions remain, including the role of repetition and word fluency in recovery, quality of life, and the impact of aphasia on (and interventions for) carers. Information on stroke lesion location and size were also excluded from the analysis. We included non-RCT and RCT data sets to support the research questions. Although non-RCT data sets pose a higher risk of bias (because of lack of randomisation), many of those we included were of high quality, reporting outcome assessor blinding and comparability of groups at baseline. The analysis prioritised IPD derived from RCT data sets, before we included IPD from non-RCT data sets. In analyses where RCT data was lacking, the non-RCT data provided an overview of the available data to date. Where RCR data was available to support the analysis, we found little indication of a difference in the findings (see Chapters 4–7).
Methodological limitations
Across the study, we undertook multiple subgroup analyses, and we acknowledge the risk of false-positive findings. The prespecified statistical analysis plan developed with the collaborators had a strong rationale for conducting the exploratory analyses in this way. We considered compensating for this risk statistically, but, given the exploratory approach, it was important to highlight all future research avenues. The findings should be interpreted in this context. The analysis approach could not consider or adjust for all possible confounders (e.g. dropout rates, interactions between age or severity and delivery of services). The examination of spontaneous recovery following aphasia in a natural history group was hampered by the lack of data availability. Ethically, it may be difficult to gather such data now in a clinically relevant population. Participants ranged from a few days to 38 years from stroke at study enrolment. We used the term ‘study entry’ to highlight this and controlled for time since stroke in the analysis. Despite these steps, it was not possible to distinguish spontaneous recovery of language from treatment-induced effects in the analysis. Aphasia researchers and therapists alike continue to work in this context.
Interpretation of the data in relation to other research
The results are in keeping with previous meta-analyses, although this IPD meta-analysis approach afforded a greater insight into the interactions between participant profile, therapy interventions and language outcomes than is possible in an aggregate data meta-analysis. Some meta-analyses were based on language-limited literature searching (e.g. English only),62–64 included RCTs only,41 included both RCT and non-RCT data sets,62 and highlighted data availability limitations.41,62
Others have suggested the importance of early intervention after stroke,62,63 reporting it to be twice as effective as spontaneous recovery.62 Gains made later after stroke were acknowledged, but were smaller.62 Some meta-analyses have suggested that ≥ 2 hours of SLT weekly is the optimal intensity,63 whereas others indicated that this may be subtherapeutic and that a minimum of 9 hours of SLT weekly is required for gains.64 Interventions that provided a total dosage in excess of 90 hours of therapy found benefits while those providing a dose of less than 44 hours did not.64
One review based on 23 case studies (57 participants), concluded that time since stroke was not a predictor of rehabilitation effect.127 A 2016 Cochrane review update41 found that intensive SLT benefited measures of overall language ability (group summary data from five RCTs) and functional language (two RCTs); however, these gains occurred alongside significantly higher numbers of dropouts from the intensive SLT compared with less intensive SLT approaches. They suggest that not all patients may be able to tolerate high-intensity SLT interventions for aphasia (4–15 hours per week).41 A 2018 SLT RCT of an SLT intervention for aphasia did not experience the same level of dropout.26
Patient and public involvement
Stroke survivors, carers and health-care professionals identified enhanced interventions for people with aphasia as a research priority.49,73 The RELEASE project sought to address this objective. The research plans were supported by organisations in the Aphasia Alliance (a UK collective of organisations supporting people with aphasia and their carers) and international counterparts (e.g. the Australian Aphasia Association). During the study, we worked closely with a group of people with aphasia and their carers based in Norwich (facilitated by Dr Simon Horton, University of East Anglia).
As a secondary data analysis project, the PPI involvement aim was not to inform the development of accessible information sheets, consent forms or appraise the acceptability of the intervention as might be expected in a primary research context,128,129 but to facilitate communication of the findings to people with aphasia, their families, health-care professionals and commissioners. We scheduled a series of meetings with the group (at the project start, mid-way and on availability of the final results) during which we shared information in an accessible format prior to meetings, providing meeting updates and opportunities for questions and comments arising. At the third and final meeting, we sought their input into future dissemination plans.
To date, the output from the group has included outlining possible routes to dissemination for people with aphasia, their families, health-care professionals and members of the public with an aphasia awareness-raising goal. Although the PPI group has had a limited influence on the secondary analysis methodologies (in keeping with the PPI aims), its input was vital to the dissemination planning stage. We will continue to seek their contribution to the development, interpretation and dissemination of the study findings. Working together with the PPI group ensures the relevance and accessibility of the findings. In addition, we will share our findings with commissioning groups in the UK. Communication with comparable international groups of people with aphasia, carers and health-care professionals will be facilitated by the RELEASE study collaborators and the Collaboration of Aphasia Trialists.
Clinical implications
The limited insights into current SLT services for people with aphasia suggest that access to rehabilitation, in the context of the current evidence base, is inadequate. The findings of this study would support that assertion. The greatest language gains observed were associated with higher-dose SLT (frequency, duration, intensity and dosage) than has been described in recent reports of current practice,69 raising the question of whether or not current levels of clinical intervention are subtherapeutic. Some subgroups of people with aphasia, however, may experience optimum language recovery in the context of SLT at lower or higher frequencies, intensities or dosage. Specific language gains may require high-intensity intervention more than others. High-quality RCTs are required to definitively address these questions.
Should these RCTs support the findings, it is unrealistic to expect that the intensity, duration and dosage that may be required for optimal language gains can be supported in the traditional model of SLT services, namely one-to-one, face-to-face contact with a qualified speech and language therapist.69 Alternative approaches to the provision and augmentation of therapy intervention regimens developed and co-ordinated by qualified therapists could be investigated and their effectiveness evaluated.130 In this context, face-to-face therapy sessions could continue to focus on specialist therapeutic tasks, assessment, prescription of home practice tasks, generalisation, training of family members to provide therapy and support language stimulation and conversational interactions.
We would welcome use of the augmented TIDieR classification framework developed during the course of this study to support the description of SLT interventions132 in the development of future clinical guidelines to support, transparent and clinically implementable therapeutic intervention recommendations for aphasia after stroke.132
Research implications
Further randomised controlled trials
Targeted RCTs of aphasia treatment interventions are required to address the many uncertainties identified in the research. We noted many high-quality non-RCT data sets, which could have greatly reduced the risk of possible bias and increased confidence in the study findings with the application of a randomisation process on recruitment of the participants.
We noted the limited availability of data sets describing interventions that targeted improvements in reading comprehension and writing or reporting of reading and writing language outcomes. Greater research focus on these language domains is warranted.
A co-ordinated series of RCTs is required to definitively address the questions raised by this exploratory research and the possibility of a SLT–language recovery dose–response relationship. Researchers should specifically consider the development of participant inclusion criteria, subgroups of interest and experimental SLT interventions in the context of these findings. Understanding of complex rehabilitation interventions delivered to a complex population can be enhanced and methodologically addressed through improvements in research design, data capture, description and reporting, and the continuation of collaborative initiatives such as the RELEASE study.
Time since stroke at enrolment and clinical relevance
We noted a trend towards better language scores with increasing time and across all domains among participants at study entry, which may suggest a risk of selection bias. Time since stroke was also a predictor of language recovery. Thus, time since aphasia onset should be considered in participant recruitment, interpretation of study findings and their clinical relevance.
Core data set
The aphasia research community recently achieved international consensus on a core outcome set, but we also require consensus on a core data set that supports adequate description of participant demographics, stroke profile and, potentially, biomarkers, alongside a comprehensive measurement of language.
Similarly, advances made in the transparent reporting of complex interventions using the TIDieR checklist could be further enhanced when reporting complex SLT interventions by including a description of the language impairment target and the theoretical approach.132 In the light of the findings from this study, details on tailoring of the SLT interventions to participants by functional relevance or level of difficulty, and the prescription of home-based practice tasks (and adherence to those practice tasks) would enhance the reporting of therapy dosage.
Legacy database
This collaborative, international, multidisciplinary initiative has resulted in the creation of a large IPD database that (subject to approvals from the contributing research gatekeepers) will continue to support future secondary-analysis aphasia research activities.
Future research
Future research targeting the evidence gaps identified in this comprehensive search, data extraction and analysis would be welcomed. The network meta-analysis highlights SLT treatment approaches lacking sufficient RCT comparisons.
Greater focus on the recruitment and documentation of non-English-speaking participants in aphasia research would enhance the representation of a clinically representative research population and provide greater insights into optimal rehabilitation approaches for people with aphasia in non-English languages and across more than one language. Greater involvement of multilingual and non-English speaking populations will require research investment in the development and validity of aphasia assessment tools for languages other than English. Supporting this endeavour would increase the international capacity for aphasia research activities, support recruitment of adequate sample sizes powered to address the research questions and inform clinical service development for non-English speaking and multilingual populations.
Recent trials have ensured that they achieved the requisite sample size and greater generalisability of the findings and engagement with the clinical speech and language therapists across multiple national sites.55,57 Although international studies are increasingly common in the context of stroke rehabilitation, the linguistic and assessment restrictions to conducting aphasia research internationally represents a specific challenge for aphasia rehabilitation researchers. Despite this, some [e.g. the Very Early Rehabilitation in Speech (VERSE) III trial72] have demonstrated the feasibility and benefits of an international recruitment strategy.
Conclusions
The RELEASE study represents the largest aphasia research database developed to date, with collated IPD on demographics and language domains following a range of SLT interventions. The exploratory findings plotted the patterns of language recovery for people with aphasia who received SLT after stroke. Time since stroke, age, severity of aphasia at baseline and sex were found to be significantly associated with language recovery in selected domains. The best language gains from baseline across language domains were associated with SLT interventions at different levels of frequency, duration, intensity and dosage. The greatest language gains were seen in the context of SLT interventions that were delivered over several days a week, for several hours weekly, for a total of 20–50 hours. Exceptions to this pattern were typically associated with a small number of participants or data sets. Some subgroups may achieve higher language gains in the context of specific SLT interventions, but these exploratory findings require further definitive investigation to enhance the delivery of SLT for aphasia after stroke for the benefit of people with aphasia, their families and health-care professionals.