Precision rehabilitation for aphasia by patient age, sex, aphasia severity, and time since stroke? A prespecified, systematic review-based, individual participant data, network, subgroup meta-analysis
Authors:   The RELEASE Collaborators, Brady Marian C , Ali Myzoon , VandenBerg Kathryn , Williams Linda J , Williams Louise R , Abo Masahiro , Becker Frank , Bowen Audrey , Brandenburg Caitlin , Breitenstein Caterina , Bruehl Stefanie , Copland David A , Cranfill Tamara B , Pietro-Bachmann Marie di , Enderby Pamela , Fillingham Joanne , Lucia Galli Federica , Gandolfi Marialuisa , Glize Bertrand , Godecke Erin , Hawkins Neil , Hilari Katerina , Hinckley Jacqueline , Horton Simon , Howard David , Jaecks Petra , Jefferies Elizabeth , Jesus Luis MT , Kambanaros Maria , Kyoung Kang Eun , Khedr Eman M , Pak-Hin Kong Anthony , Kukkonen Tarja , Laganaro Marina , Lambon Ralph Matthew A , Charlotte Laska Ann , Leemann Béatrice , Leff Alexander P , Lima Roxele R , Lorenz Antje , MacWhinney Brian , Shisler Marshall Rebecca , Mattioli Flavia , Maviş İlknur , Meinzer Marcus , Nilipour Reza , Noé Enrique , Paik Nam-Jong , Palmer Rebecca , Papathanasiou Ilias , Patricio Brigida , Pavão Martins Isabel , Price Cathy , Prizl Jakovac Tatjana , Rochon Elizabeth , Rose Miranda L , Rosso Charlotte , Rubi-Fessen Ilona , Ruiter Marina B , Snell Claerwen , Stahl Benjamin , Szaflarski Jerzy P , Thomas Shirley A , van de Sandt-Koenderman Mieke , van der Meulen Ineke , Visch-Brink Evy , Worrall Linda , Harris Wright Heather 
Published: April 2022

Background: Stroke rehabilitation interventions are routinely personalized to address individuals’ needs, goals, and challenges based on evidence from aggregated randomized controlled trials (RCT) data and meta-syntheses. Individual participant data (IPD) meta-analyses may better inform the development of precision rehabilitation approaches, quantifying treatment responses while adjusting for confounders and reducing ecological bias. Aim: We explored associations between speech and language therapy (SLT) interventions frequency (days/week), intensity (h/week), and dosage (total SLT-hours) and language outcomes for different age, sex, aphasia severity, and chronicity subgroups by undertaking prespecified subgroup network meta-analyses of the RELEASE database. Methods: MEDLINE, EMBASE, and trial registrations were systematically searched (inception-Sept2015) for RCTs, including ⩾ 10 IPD on stroke-related aphasia. We extracted demographic, stroke, aphasia, SLT, and risk of bias data. Overall-language ability, auditory comprehension, and functional communication outcomes were standardized. A one-stage, random effects, network meta-analysis approach filtered IPD into a single optimal model, examining SLT regimen and language recovery from baseline to first post-intervention follow-up, adjusting for covariates identified a-priori. Data were dichotomized by age (⩽/> 65 years), aphasia severity (mild–moderate/ moderate–severe based on language outcomes’ median value), chronicity (⩽/> 3 months), and sex subgroups. We reported estimates of means and 95% confidence intervals. Where relative variance was high (> 50%), results were reported for completeness. Results: 959 IPD (25 RCTs) were analyzed. For working-age participants, greatest language gains from baseline occurred alongside moderate to high-intensity SLT (functional communication 3-to-4 h/week; overall-language and comprehension > 9 h/week); older participants’ greatest gains occurred alongside low-intensity SLT (⩽ 2 h/week) except for auditory comprehension (> 9 h/week). For both age-groups, SLT-frequency and dosage associated with best language gains were similar. Participants ⩽ 3 months post-onset demonstrated greatest overall-language gains for SLT at low intensity/moderate dosage (⩽ 2 SLT-h/week; 20-to-50 h); for those > 3 months, post-stroke greatest gains were associated with moderate-intensity/high-dosage SLT (3–4 SLT-h/week; ⩾ 50 hours). For moderate–severe participants, 4 SLT-days/week conferred the greatest language gains across outcomes, with auditory comprehension gains only observed for ⩾ 4 SLT-days/week; mild–moderate participants’ greatest functional communication gains were associated with similar frequency (⩾ 4 SLT-days/week) and greatest overall-language gains with higher frequency SLT (⩾ 6 days/weekly). Males’ greatest gains were associated with SLT of moderate (functional communication; 3-to-4 h/weekly) or high intensity (overall-language and auditory comprehension; (> 9 h/weekly) compared to females for whom the greatest gains were associated with lower-intensity SLT (< 2 SLT-h/weekly). Consistencies across subgroups were also evident; greatest overall-language gains were associated with 20-to-50 SLT-h in total; auditory comprehension gains were generally observed when SLT > 9 h over ⩾ 4 days/week. Conclusions: We observed a treatment response in most subgroups’ overall-language, auditory comprehension, and functional communication language gains. For some, the maximum treatment response varied in association with different SLT-frequency, intensity, and dosage. Where differences were observed, working-aged, chronic, mild–moderate, and male subgroups experienced their greatest language gains alongside high-frequency/intensity SLT. In contrast, older, moderate–severely impaired, and female subgroups within 3 months of aphasia onset made their greatest gains for lower-intensity SLT. The acceptability, clinical, and cost effectiveness of precision aphasia rehabilitation approaches based on age, sex, aphasia severity, and chronicity should be evaluated in future clinical RCTs.