A group memory rehabilitation programme for people with traumatic brain injuries: the ReMemBrIn RCT

Usual care

All participants received their usual clinical care during the trial. Based on our knowledge of the recruiting sites, we expected that the majority of participants would no longer be receiving any formal rehabilitation but that they may be attending employment rehabilitation services or self-help groups or receiving support from specialist charities, such as Headway. Any additional interventions that people received were noted in the SUQ completed at the follow-up assessments.

Memory rehabilitation

The intervention was offered in groups of between four and six participants. Each group was led by an AP trained to deliver the intervention. Sessions were held at NHS sites or community venues. Participants were offered 10 group memory rehabilitation sessions, lasting approximately 1.5 hours each, which were planned to take place once a week for 10 weeks. However, sessions could be rearranged if necessary (e.g. because of staff or participant absence). The sessions followed a treatment manual. 18 The intervention included restitution strategies to retrain memory functions, including attention retraining (such as letter cancellation), and strategies to improve encoding and retrieval (such as deep-level processing). Compensation strategies were taught, including mnemonics (such as chunking, use of first letter cues, rhymes), use of external devices (such as diaries, mobile phones and calendars) and ways of coping with memory problems. The importance of ‘errorless learning’ (not making errors while learning new material and, therefore, preventing learning the errors)62 was also taught. The emphasis was on identifying the most appropriate strategies to help individuals overcome their memory problems and on providing participants with a range of memory techniques that they could adapt and use depending on their needs. This intervention provided an opportunity for revision of strategies taught during inpatient rehabilitation and discussion of their application in a community setting.

Treatment fidelity

The fidelity of the group rehabilitation programme was assured in a number of ways:

• Manualised treatment. The group memory rehabilitation programme followed a manual (see Report Supplementary Material 1) that was developed and tested in the pilot study. A detailed description of the manual has been published. 18,23 The manual was accompanied by facilitator notes to guide delivery of the sessions (see Report Supplementary Material 2).

• Training and supervision. Staff delivering the intervention (APs) were psychology graduates with clinical experience. A clinical psychologist provided study-specific training on conducting baseline assessments and the delivery of the intervention. In addition, monthly teleconferences between all APs, a clinical psychologist and NCTU staff provided an opportunity for peer group supervision. Furthermore, additional monthly one-to-one supervision with a clinical psychologist allowed for discussion of specific challenges relating to treatment or assessment. To ensure continuity and consistency, when staff changes occurred, old staff completed a ‘handover’ document for new staff, who were trained by the same trainers.

• Fidelity assessment. Formal fidelity assessment of the group memory rehabilitation was undertaken through analysis of video recordings of treatment sessions. Intervention sessions were video recorded by APs facilitating the groups. APs were asked to video record all treatment groups, unless it was the first group run by the AP or participants had not given consent to be recorded. Practices for video recording drew on guidance on minimising the intrusiveness of the recording. 63,64

Sessions were selected for analysis in order to include sessions from the start, middle and end of the 10-week course and from each site. As far as possible, only recordings that covered a complete session were analysed. A coding schedule was developed based on the components of treatment described in the manual, listing possible activities for both the APs and participants (see Appendix 3).

A distinction was made between non-rehabilitation activities (e.g. social chat, information about sessions, preparing tasks or materials) and rehabilitation activities (e.g. discussing educational material, recap of previous session). An independent researcher coded the videos using a time sampling procedure. Observations were made on the minute, every minute, throughout the video recording. For each observation, the activities of the AP and participants were given the appropriate activity code. A sample of coding was checked by another observer and discrepancies were resolved by discussion. Data from coding sheets were entered into the SPSS statistics programme for analysis (version 21; IBM Corporation, Armonk, NY, USA).

Requirements for usual care were not specified and so no measures of fidelity were applied.

Trial Management Group

The TMG comprised the co-chief investigators and members of the NCTU responsible for the running of the trial, who met regularly throughout the trial. This group was responsible for the day-to-day running of the trial.

Trial Steering Committee

The TSC was responsible for overseeing the conduct of the study. The TSC had an independent chairperson and five independent members. Independent members were rehabilitation professionals and patient/carer representatives who were not otherwise involved in the trial. Members of the study team, including the chief investigator, co-chief investigator, service user co-applicant and trial manager, were also part of the TSC. The TSC advised on recruitment strategies, monitored the progress of recruitment and checked adherence to the study protocol. Observers from the funder and the sponsor were invited to TSC meetings.

Data Monitoring Committee

The DMC was an independent group, the members had no other involvement with the study. Members of this committee included two rehabilitation professionals and an experienced study statistician. The role of the DMC was to safeguard the interests of trial participants, with particular reference to the safety of the intervention, monitor the overall progress and conduct of the trial and assist and advise the investigators to protect the validity and credibility of the trial.

The TSC and the DMC met independently of each other, with the DMC providing reports to the TSC.

Safety monitoring

The risks of the study were assessed during protocol development. The assessment of memory may have made participants aware of memory problems that they did not know that they had. As a result, the main risk associated with this trial was considered to be distress caused by this realisation. However, such distress was considered unlikely and any distress caused was deemed likely to be mild. Overall, therefore, the risk of the trial was assessed as negligible. As a result, data on adverse events or serious adverse events were not collected in this study. The independent DMC instead was provided with a report detailing hospital and GP visits (either related to TBI or otherwise), recorded from participant-reported SUQs for all participants, and any deaths. This was agreed by the sponsor, the Research Ethics Committee, the DMC and the TSC.

‘Notable events’ occurring during both assessments and treatment were recorded throughout the trial. Notable events were those that were assessed by the APs or RAs as being out of the ordinary, such as problems arising during group sessions or issues that might pose a risk to participants or researchers. These were reviewed by the study team on an ongoing basis and were reported to the DMC/TSC during routine meetings.

Resource use and costs

Resource use and associated costs were calculated across the following broad categories:

• the implementation and delivery of the group-based memory rehabilitation programme

• health and personal social care resource use.

All resource use data were valued in Great British pounds using published unit costs85–87 at 2016 prices. If a 2016 unit cost was not available, a unit cost from a previous version (e.g. an earlier edition of the Unit Costs of Health and Social Care) was used and inflated to 2016 costs using the Bank of England inflation calculator. 88

Costs associated with the implementation and delivery of the group-based memory rehabilitation programme

We estimated the cost of implementation and delivery of the intervention during the trial using information from the trial team and data obtained within the trial (e.g. number of participants). The key resources and associated costs of delivering the intervention focused on the opportunity costs of:

• AP training to deliver the intervention

• delivery of the intervention by APs to trial participants.

We assumed that, in standard clinical practice, the intervention would be delivered in a NHS setting, thus the costs of travel and room hire and other capital costs were not included. Resources and associated costs related to research and the management and administration of the trial were excluded. Costs of supplying course booklets, stationery and refreshments were included. No provision for supervision was included in the intervention cost. It was instead assumed that the costs and resources related to supervision were part of standard clinical practice for the delivery of any intervention by APs.

The skill mix, time and grade of staff involved in delivering the intervention were obtained from information collated by the trial team. These costs were aggregated to give a total cost, given the number of groups to which participants were allocated and the number of sessions offered.

Individual-level resource use and associated costs within the group memory rehabilitation programme

We assessed individual-level resource use using the SUQ, as previously described in Chapter 2. Resource use was initially summated across each time point for each individual into discrete categories (primary care, medication use within primary care, secondary care).

For primary care costs, we used published unit costs based on average contact times. 85 We obtained NHS net prices for medications from the British National Formulary (BNF). 86 When the dosage and prescription length were recorded by the participant, the cost of the medication was calculated. When the dosage or prescription length was either not recorded by the participant or unclear, the cost of the standard adult dosage as per the BNF was used. We calculated the cost of secondary care attendances by applying unit costs from national published sources87 to the usage reported on the questionnaires. When possible for inpatient admissions, the type of procedure and length of stay were matched and the national average unit cost used. When no length of stay was stated, the lowest national average unit cost was used, based on the lowest case-mix classification (CC) score (i.e. 0–1). As only a small number of participants did not report any length of stay, this approach was preferred to a weighted cost approach, which would have substantially overestimated the cost of service use contacts. When an unspecified or ambiguous visit to a hospital was indicated, but no length of stay was stated, an average general surgery cost was used to ensure that these contacts were appropriately captured.

Although the SUQ allowed participants to differentiate between resource use as a consequence of memory problems and resource use for other reasons (e.g. other comorbidities), this information was not obtained for medication use. We decided, in consultation with the trial team, that it would be difficult for participants to classify resource use on the basis of whether it was for memory problems or for other problems. Therefore, the decision was made to use total resource use (i.e. service use because of memory problems and for other reasons) within the base-case analysis. Appropriate sensitivity analysis was undertaken to assess the impact of including resource use attributed to memory problems only.

Resource use and costs were summated to give an overall cost for the memory rehabilitation arm (including intervention costs) and usual-care arm over the trial period (12 months), with an interim assessment at the 6-month follow-up point also reported to reflect the time points of interest. The mean total cost and difference in mean total cost (with 95% CIs) per participant between the memory rehabilitation arm and the usual-care arm were compared using the two-tailed Student’s t-test, following the ITT principle.

A description of unit costs associated with service resource and medication use is presented in Appendices 20 and 21, respectively.

Health utilities and quality-adjusted life-years

Health-related quality-of-life data were collated using the EQ-5D-5L questionnaire, as described in Chapter 2. The reported EQ-5D-5L values were used to derive utilities based on the UK social tariff. 89 Individual-level utility scores across each assessment point were summated for the memory rehabilitation and usual-care arms, with QALYs for each patient calculated based on the utility scores at different points using the AUC approach. We assumed linear interpolation between the measurement points.

Summary statistics across each time point were used to describe and compare QALYs between the two arms from baseline to 12 months for the primary analysis, with additional analysis to derive QALYs from baseline to the 6-month follow-up. The impact of a baseline imbalance in utilities was examined, with adjusted analyses on similar covariates (baseline score, treatment arm and site) undertaken, commensurate with the statistical analysis methods of the clinical outcomes. Mean utilities and QALYs gained per participant were evaluated between the memory rehabilitation arm and the usual-care arm using the difference-in-difference approach and compared using the Student’s t-test.

Clinical outcomes

The primary outcome data (EMQ-p) and GHQ-30 scores were analysed with the difference in scores (points) calculated (as described in Chapter 2) at the 6-month follow-up (as per the primary clinical analysis) and at 12 months (to assess whether an improvement was maintained over time). The analysis of the EMQ-p is commensurate with the clinical analysis, with a difference-in-difference approach adopted to determine the incremental effect of the intervention compared with usual care. For the analysis of the GHQ-30, the GHQ-30 (0–0–1–1) scoring methodology was applied. This differs from the clinical analysis, which adopted the Likert (0–1–2–3) scoring methodology. Higher scores on the EMQ-p are indicative of more frequent memory problems and higher scores on the GHQ-30 are indicative of greater psychological distress. Therefore, ‘improvement’ over time would be characterised by a decreasing score.

Missing data

The problems concerning missing data are particularly relevant to health economic analysis as missing items relating to health-care service usage may undervalue the total costs, whereas missing outcome data may be correlated with effects, as those individuals without information may be systematically different from those for whom all information is observed. 90 A complete case analysis would therefore result in meaningful data being excluded. 90 We therefore adopted appropriate techniques to provide a comprehensive investigation of the impact of missing data on our estimations of cost-effectiveness.

For the questionnaires used within the economic analysis (i.e. EQ-5D-5L, EMQ-p and GHQ-30) we followed the same rules for missing data as applied to the analysis of clinical outcomes (see Chapter 2). To ensure that comparable consideration was given to missing data in relation to the SUQ, we devised similar rules with the trial team.

For both costs and outcomes, two imputation methods were used for the health economic analysis. Simple imputation using the site-specific treatment arm mean and MICE were undertaken on costs and outcomes for both the 6-month follow-up and the 12-month follow-up to impute missing items. Mean imputation provides a single estimate for each missing item. However, it is unable to account for the uncertainty inherent in missing data, resulting in a smaller standard error (SE), and can result in biased estimates because of covariance and correlations being decreased in magnitude compared with alternative methods. The multiple imputation method used was similar to the imputation of the primary outcome data performed, that is, chained equations were undertaken separately for each allocated arm under the assumption that data were missing at random, using similar predictor variables (with baseline EQ-5D-5L score used) with similar data sets included and results of imputed sets combined following Rubin’s rules. 91 Because of the typically skewed distribution of cost data, predictive mean matching was used. Missing outcome data were imputed using truncated regression to restrict imputed scores to the range of valid scores for each outcome.

For the base-case cost-effectiveness analyses, we used the multiply imputed data to construct incremental cost-effectiveness ratios (ICERs). The non-imputed and mean imputed data are presented to fully reflect the impact on the base-case ICERs when different scenarios for missing data are considered.

Incremental-cost-effectiveness analysis

As summarised in the description of the within-trial evaluation, a series of cost-effectiveness analyses were undertaken, with a cost–utility analysis undertaken as the primary analysis. This comparative analysis of incremental costs and effects can be summarised in terms of an ICER.

The ICER can be represented as:

where C₁ and E₁ are the costs and effects of the memory rehabilitation arm, respectively; C₀ and E₀ are the costs and effects of the usual-care arm, respectively; and ΔC and ΔE are the incremental costs and effects of the intervention compared with usual care.

The ICER is reported to determine the cost-effectiveness of the intervention compared with competing alternatives and to aid decision-making. Although NICE84 reports a base cost-effectiveness threshold of £20,000 per QALY, cost-effectiveness is a spectrum rather than a dichotomy, with the maximum threshold increasing dependent on circumstances. The reported ICERs from our analysis are presented to assist the decision-making process and are not an absolute statement on whether the intervention can be deemed cost-effective.

We also calculated net monetary benefits (NMBs) based on the following equation:

The NMB represents the value of the intervention in monetary terms given a willingness-to-pay (WTP) threshold, λ. 91 When the incremental NMB, calculated as the difference in NMB between the intervention and usual care, is positive, the intervention is identified as cost-effective at the given threshold, relative to usual care. 92

For the cost-effectiveness analyses (i.e. incremental cost per point improvement in EMQ-p and GHQ-30 scores), no accepted WTP threshold could be identified. However, as the WTP threshold is based on important end points of relevance and importance to the assessment of the effect of memory problems, decision-makers and clinicians can judge the results against different thresholds as part of a full examination of cost-effectiveness.

Sensitivity analysis

A series of one-way sensitivity analyses were undertaken to assess the impact of parameter and methodological uncertainty on the estimates of cost-effectiveness. For primary and secondary outcomes, we assessed the impact on the base-case ICER of altering key parameters (i.e. costs, QALYs and outcomes scores) based on lower and upper 95% CIs for incremental costs and outcomes.

We also assessed the extent of uncertainty based on imputation method, as documented earlier. Scenario analysis was conducted to ascertain the potential impact of changes to input parameters (as measured by the EMQ-p and GHQ-30) on the base-case ICER. Sensitivity analyses of the intervention cost were conducted on the available data case analysis.

Bootstrapping was undertaken to address the joint uncertainty and impact on the ICER; 1000 simulations were undertaken using random sampling of the distributions of costs and outcomes, presented on a cost-effectiveness plane. The cost-effectiveness plane is presented as a scatterplot of the point estimates obtained as a result of the 1000 runs depicted in four quadrants (see Appendix 22), which can be summarised as follows:

1. North-west (upper-left) quadrant – the intervention is dominated by usual care. The intervention is more costly and less effective than usual care.

2. North-east (upper-right) quadrant – further evaluation required. The intervention is more costly and more effective than usual care. The ICER is computed to assess whether the net incremental health gain is worth the incremental cost.

3. South-west (lower-left) quadrant – further evaluation required. The intervention is less costly and less effective than usual care. The ICER is computed to assess whether the cost saving is worth the net incremental health loss.

4. South-east (lower-right) quadrant – the intervention is dominant compared with usual care and unambiguously preferred to usual care. The intervention is less costly and more effective than usual care.

For consistency with the cost-effectiveness plane for QALYs, the incremental effect for the EMQ-p and GHQ-30 was reversed (i.e. multiplied by –1) such that a positive value was representative of an improvement in everyday memory or mood. Cost-effectiveness acceptability curves (CEACs) were produced to present the probability of the intervention being considered cost-effective at alternative WTP thresholds. For the cost per QALY CEAC, the WTP threshold based on NICE guidance84 was used. No similar WTP threshold exists for the clinical outcomes.

Modelling approach

We developed a Markov model given that TBIs are considered to have a disease and treatment pathway consistent with chronic health conditions (e.g. with evolving progression of the condition over time). The decision-analytic Markov model was developed using Microsoft Excel^® 2013 with coding in Visual Basic for Applications (Microsoft Corporation, Redmond, WA, USA). The Markov model simulated costs and QALYs over a minimum 5-year time horizon using four mutually exclusive health states (low, moderate, high and death). As the time horizon exceeded 12 months we discounted all future costs and QALYs at the UK Treasury discount rate of 3.5% per year, as recommended by NICE. 84

The cost and utility data reported at the 12-month follow-up within the trial were used alongside external data such as UK life tables and standard mortality ratios to estimate longer-term costs and QALYs. Time horizons of 5 and 10 years were chosen for the analysis although the model was constructed to undertake a lifetime horizon should suitable data be available in the future. Although this was an amendment from the original protocol, in which a lifetime horizon was proposed, we chose this approach (1) based on the availability of plausible estimates of longer-term effects from external literature sources and (2) because, when necessary, appropriate clinical assumptions could be made by the trial team.

We categorised psychological distress into three mutually exclusive states of no/mild distress, moderate distress and severe distress, pro-rating the categories defined by Rai et al. 93 for the GHQ-12 to the GHQ-30 as follows:

• GHQ-30 scores of < 5.5 were classified as no/mild distress

• GHQ-30 scores between 5.5 and 17.5 were classified as moderate distress

• GHQ-30 scores of ≥ 17.5 were classified as severe distress.

Participants could also transition to a fourth state of death, which is an absorbing state with participants unable to transition out of this state.

Model structure

The basic outline of the Markov model used to evaluate the longer-term cost-effectiveness of the intervention is illustrated in Appendix 23. For the memory rehabilitation and usual-care arms, separate Markov processes with different input parameters were obtained. The same structure, depicted in Appendix 23, would, however, apply.

We assumed that the sample adhered to the trial protocol. For each 6-month cycle, individuals were categorised into one of three mood states based on their GHQ-30 score or into the absorbing death state. We assumed that psychological distress in individuals with TBI can either worsen or improve, that is, the GHQ-30 score could either increase or decrease from the value observed at the previous time point. Moreover, transitions from the high mood state to the low mood state (or vice versa) were permitted in addition to sequential transitions, that is, high to moderate to low. Aside from death, we assumed that there were no intervention-related adverse events that impacted on an individual’s state of psychological distress.

Model inputs

The base-case analysis was estimated using a cohort of 10,000 patients. The population was consistent with the trial, that is, men represented 72% of the model cohort and the mean age at entry was 45 years. Base-case transition probabilities were defined by those observed in the trial between baseline and 6 months’ follow-up and between 6 months’ and 12 months’ follow-up. For intervals beyond the 12-month within-trial horizon, we assumed that the 6-month to 12-month transition probabilities would persist at intervals beyond 12 months. This assumption was made because of a lack of published data beyond the 12-month follow-up.

To account for missing items observed in the trial, mean imputed data were used, despite the limitations highlighted earlier, to provide a single transition for each individual and prevent scenarios in which an individual occupied multiple states at a given time point. This provided a single set of transition probabilities at each time point. Sensitivity analysis was conducted to determine how changes in transition probabilities influenced the ICER.

Details of the model parameters used are presented in Appendix 24. A summary of the base-case model inputs and one-way sensitivity analyses is presented in Table 13.

Clinical/epidemiological inputs

No deaths were reported in the trial. We therefore assumed that patients would not be at an increased risk of death from the intervention. Additionally, the model did not include any provision for the occurrence of serious adverse events, as these were not assessed within the trial. In the model, all-cause age-related mortality rates were obtained from the Office for National Statistics (ONS),94 based on mid-year population estimates for 2013–15. Considering that individuals with a TBI are recognised to have a higher all-cause mortality rate and shorter life expectancy than the general population,93,95 we adjusted the general population mortality using the TBI standardised mortality ratio (SMR) presented by Brooks et al. 96

Costs

All costs were based on the within-trial costs reported (see Appendix 25). Costs associated with each health state defined by the model included the costs relating to delivery of the intervention and any health-care service usage recorded by participants over the preceding 6-month interval. For cycles beyond the in-trial 12-month horizon, costs were assumed to be the same as for the 6- to 12-month cycle. No provision was made in the model for any top-up sessions relating to the intervention.

Utilities

The model applied different utility values to each of the non-dead health states, differentiated by trial arm. In accordance with the manner in which costs were handled, all utilities were based on those observed in the within-trial analysis reported. For cycles beyond the within-trial 12-month horizon, utilities were assumed to be the same as for the 6- to 12-month cycle.

Incremental cost-effectiveness ratio

Incremental cost-effectiveness ratios were calculated as in the within-trial analysis, based on a 5- and 10-year time horizon. As this was a cost–utility analysis, we applied the same approach as in the assessment of the base-case results against the WTP threshold set out by NICE. 84

Sensitivity analysis

Similar sensitivity analyses were conducted as outlined for the within-trial evaluation.

We conducted a series of one-way sensitivity analyses by manipulating the values of the main parameters in the model (i.e. costs, QALYs and transition probabilities) and assessing the subsequent impact on the ICER. Table 13 presents a list of the one-way sensitivity analyses conducted.

In general, the upper and lower values of the input parameters were arbitrarily chosen, but were considered appropriate given the uncertainty inherent in the parameter values. The lower discount rate of 1.5% is consistent with NICE guidelines. 84 Costs and QALYs were discounted at the same rate under all scenarios. Sensitivity analyses on transition probabilities also affect the probability that an individual remains within their current state; however, they do not affect the probability of transitioning to the death state.

To account for the simultaneous uncertainty regarding the input parameters, a probabilistic sensitivity analysis was conducted. Cost-effectiveness planes and CEACs illustrating the probability that the intervention is cost-effective across a range of threshold values were produced.

Impact of missing data on cost estimations

Service use questionnaire data were obtained for 98.8% of participants at baseline (see Appendix 27). However, at the 6- and 12-month follow-ups, questionnaires were missing for approximately 20% and 29% of participants, in each arm, respectively, with more missing data in the usual-care arm (36%) than in the memory rehabilitation arm (29%) at the 12-month follow-up. The planned approach to missing data was subsequently adopted.

Although numerical differences between the trial arms were seen depending on the imputation method used, there was no statistically significant impact on the total costs, with the memory rehabilitation arm showing a higher total mean cost per participant at the 12-month follow-up. With the inherent issues associated with skewed costs, imputed costs were subsequently bootstrapped to derive means and 95% CIs to be used in the base case (Table 16).

EuroQol-5 Dimensions five-level version utilities

The EQ-5D-5L utility scores and QALY increments, based on AUC analysis, across the trial assessment points, based on the available cases for the memory rehabilitation and usual-care arms, are presented in Table 17.

At 6 months, small QALY losses were observed for both arms; the incremental QALY gain of 0.003 in the memory rehabilitation arm compared with the usual-care arm was not significant at the 5% level (p = 0.154). At 12 months, small QALY loses were observed, with a small incremental QALY gain of 0.004 in the usual-care arm compared with the memory rehabilitation arm, which was not significant at the 5% level (p = 0.743). The incremental QALY gains calculated from the mean imputed and multiply imputed data are analogous to those calculated from the available cases presented above, with a small gain for the memory rehabilitation arm at 6 months and a small gain for the usual-care arm at 12 months.

Impact of missing data

There was 100% completion of the EQ-5D-5L questionnaire at baseline, with the number of missing data increasing at 6 months and 12 months across both arms. No clear pattern of missing data was evident. Most participants who missed one follow-up assessment had another follow-up assessment available. A descriptive profile of EQ-5D-5L questionnaire completion is presented in Appendix 28.

When the EQ-5D-5L utility and subsequent QALY gains were examined using the imputation methods, there were no statistically significant differences in within-group utility scores or between-group QALY gains at either the 6-month follow-up or the 12-month follow-up. Table 18 presents the results based on multiple imputation; the results of the mean imputation are presented in Appendix 29.

Similar to the results presented in Table 17, there was a small QALY loss in both arms at 6 months’ follow-up (memory rehabilitation: –0.003, 95% CI –0.013 to 0.007; usual care: –0.007, 95% CI –0.0018 to 0.004). At the 12-month follow-up, this translated into a small QALY gain in the usual care arm (0.004, 95% CI –0.017 to 0.025) compared with a small QALY loss in the memory rehabilitation arm (–0.007, 95% CI –0.025 to 0.012). These differences did not reach statistical significance, with p-values of 0.536 and 0.442 at 6 months and 12 months, respectively.

Impact of missing data

There were missing data within the questionnaires at each of the follow-up assessments. When the imputation methods were examined, numerical differences were seen but these did not demonstrate any statistically significant differences between the trial arms. The results using the multiply imputed data are presented in Table 20 and mean imputations for the EMQ-p and GHQ-30 are reported in Appendices 30 and 31, respectively.

Reductions in the multiply imputed EMQ-p score were observed for both the memory rehabilitation arm and the usual-care arm at 6 and 12 months’ follow-up. These results are commensurate with those presented in the analysis of clinical outcomes. The difference was not statistically significant at either 6 months’ (p = 0.297) or 12 months’ (p = 0.560) follow-up.

For the GHQ-30 score, although a reduction was observed in the memory rehabilitation arm at both 6 and 12 months’ follow-up relative to baseline, an increase was observed relative to baseline in the usual-care arm at both time points. This indicates an improvement in mood for the memory rehabilitation arm compared with a worsening in mood for the usual-care arm. There was a worsening in mood for both the memory rehabilitation arm and the usual-care arm between the 6-month follow-up and the 12-month follow-up. Despite using the GHQ (0–0–1–1) scoring rather than the Likert (0–1–2–3) scoring, these results are broadly comparable to the clinical outcomes, with no statistically significant difference in GHQ score within or between arms at either the 6-month follow-up or the 12-month follow-up.

Incremental cost per point improvement in EMQ-p and GHQ-30 scores at 6 and 12 months

Table 22 presents the ICERs for the EMQ-p and GHQ-30, respectively. As higher scores in the EMQ-p represent more frequent forgetting in daily life, and higher scores in the GHQ-30 indicate more psychological distress, negative incremental effects will be observed where the intervention is more effective than usual care. To calculate appropriate ICERs consistent with those for the EQ-5D-5L presented above, the denominator of the equation presented earlier is multiplied by –1.

For both the EMQ-p and the GHQ-30, in the primary analysis based on multiply imputed data at 12 and 6 months, the intervention dominated usual care because of non-statistically significant lower costs and improved EMQ-p and GHQ-30 scores. Again, uncertainty arises, with the results varying based on the imputation method used.

Sensitivity analysis

Sensitivity analysis using the upper and lower 95% CI bounds for the primary cost per QALY gained analysis is presented in Appendix 32. For two of the four scenarios, the intervention was dominated by usual care (higher costs and smaller effects for the intervention), namely when the upper 95% CI for both costs and outcomes was used and when the upper bound for costs was compared with the lower bound for QALYs.

In summary, the results suggest that the findings are not robust to changes in these parameters.

A further sensitivity analysis (based on available cases) was conducted on the intervention cost by including the costs of AP supervision by a clinical psychologist. Based on the recommendations for good practice presented by the British Psychological Society,97 we assumed that a minimum of three one-to-one supervision sessions of 1 hour were required at each site for the 10 weekly sessions. For a band 8a clinical psychologist at £66 per hour and a mid-band 5 AP at £35 per hour,85 a total of £2727 is incurred in addition to the total cost of rehabilitation presented in Table 14. The effect on the total cost and the ICER is presented in Table 23.

Taking into account these changes to the intervention cost, the intervention was found to be dominated by usual care at 12 months; at 6 months the ICER was £18,771 per QALY gained (Table 24).

The results of the bootstrapped replications are presented as a cost-effectiveness plane and corresponding CEAC for the primary cost–utility analysis (cost per QALY). As the multiply imputed base case for the EMQ-p and GHQ-30 at both 6 months and 12 months, presented in Table 22, indicates dominance of the intervention (lower cost and higher effects than usual care), cost-effectiveness planes and CEACs are not presented for the secondary cost-effectiveness analyses. The cost-effectiveness plane for cost per QALY gained is presented as a scatterplot of the point estimates obtained from the 5000 runs, depicted as quadrants (north-east, south-east, south-west and north-west), as illustrated in Appendix 22. The CEAC graph shows the probability of the intervention being considered cost-effective at different monetary thresholds.

Figures 2 and 3 present the cost-effectiveness plane and CEAC for the incremental cost per QALY gained at 12 months, respectively.

FIGURE 2.

Cost-effectiveness plane for the bootstrapped incremental cost per QALY gained at 12 months. Reproduced from das Nair et al. 82 This is an Open Access article distributed in accordance with the terms of the Creative Commons Attribution (CC BY 4.0) license, which permits others to distribute, remix, adapt and build upon this work, for commercial use, provided the original work is properly cited. See: http://creativecommons.org/licenses/by/4.0/.

Reproduced from das Nair et al. 82 This is an Open Access article distributed in accordance with the terms of the Creative Commons Attribution (CC BY 4.0) license, which permits others to distribute, remix, adapt and build upon this work, for commercial use, provided the original work is properly cited. See: http://creativecommons.org/licenses/by/4.0/.

FIGURE 3.

Cost-effectiveness acceptability curve for the bootstrapped incremental cost per QALY gained at 12 months.

Figure 2 characterises the uncertainty in the cost-effectiveness analysis, with point estimates distributed across all four quadrants. The largest proportion of estimates is located in the south-west quadrant, consistent with the intervention being less costly and less effective than usual care. The associated CEAC in Figure 3 shows that, at a threshold value of ≤ £30,000 per QALY gained, the probability that the intervention is cost-effective is 24.5%. At a threshold of £20,000 per QALY gained, the probability of cost-effectiveness is 29.0%. The cost-effectiveness plane and corresponding CEAC for the additional analysis at 6 months are presented in Figures 4 and 5, respectively.

FIGURE 4.

Cost-effectiveness plane for the bootstrapped incremental cost per QALY gained at 6 months.

FIGURE 5.

Cost-effectiveness acceptability curve for the bootstrapped incremental cost per QALY gained at 6 months.

In accordance with the 12-month results presented in Figure 2, at 6 months the cost-effectiveness plane presented in Figure 4 further demonstrates the uncertainty inherent in the cost-effectiveness results, with all four quadrants populated. In contrast to the 12-month analysis, the largest proportion of estimates is located in the south-east quadrant, consistent with the intervention being less costly and more effective than usual care; the intervention dominates usual care. The incremental effect is, however, small. The associated CEAC presented in Figure 5 illustrates that, at a WTP threshold of £20,000 per QALY gained, the intervention has a 68.1% probability of being cost-effective. At a higher WTP threshold of £30,000 per QALY gained, the intervention has a 70.6% probability of being cost-effective.

It should, however, be noted that bootstrapped replications of the cost per point improvement ICERs for the EMQ-p and GHQ-30 based on mean imputed data produced cost-effectiveness planes that were somewhat analogous to those presented in Figures 2 and 3 for the cost–utility analysis. Estimates are spread across all four quadrants, further demonstrating the uncertainty observed within the results. For both secondary outcomes at 12 months and 6 months, the largest proportion of point estimates is located in the north-east and south-east quadrants, associated with the intervention being more effective than usual care.

In Table 22 the base-case cost-effectiveness analyses of the EMQ-p and GHQ based on multiply imputed data found that the intervention dominated usual care at both 6 months and 12 months. The resulting cost-effectiveness planes for these outcomes show the largest proportion of bootstrapped estimates in the south-east quadrant, consistent with the intervention being less costly and more effective than usual care. The probability of intervention dominance based on the proportion of bootstrapped estimates in the south-east quadrant of the cost-effectiveness plane was 43.9% and 50.1% for the EMQ-p and 43.5% and 50.8% for the GHQ-30 at 6 and 12 months’ follow-up, respectively.

For both secondary health economic outcomes, the probability of dominance at 6 months is larger than that at 12 months, consistent with the larger effect observed for the shorter time horizon. Similar levels of dominance are, however, observed for the EMQ-p and GHQ.

Motivation for taking part

Most participants appeared to be driven to take part in the study by altruism. Many spoke of wanting to help others:

I’m just helping you guys out so that, so that what you can get can help somebody else out, you know, in the future.

01003, male, 58 years, usual care

So to go onto this [study] was good because I thought if this gets other people out of a situation that I was in then that’s why I wanted to do it.

06049, male, 68 years, usual care

Participants also thought that by taking part in the study they would receive some information about their memory problems and some help to deal with these problems:

It was a matter of floundering around thereafter [after discharge from hospital], er that’s why when this [study] came up we jumped at the opportunity to take part.

04005, male, 56 years, intervention

I wanted to get as much information as I could really about how it [brain injury] affects me and how I can deal with it. So that was my idea of going along with it [the study] in the first place.

05042, male, 51 years, intervention

Trial procedures

Participants had positive feedback regarding the organisation of the trial. In addition, the qualitative study was praised for providing an opportunity to raise more attention about TBI and memory rehabilitation, including the need for increased funding for such services:

From the practical viewpoint I thought the study was done well. You’re kept informed people, errm, kept appointments, etc. it was all organised, kept to there’s no issues there.

04010, male, 55 years, usual care

I’m very pleased that I’ve been part of this feedback . . . I think it [trial] is a very good thing to do I think more emphasis, more pressure on the powers that be to allocate more funding to this [TBI memory rehabilitation] because it’s very important and it does not receive anywhere near the amount of attention that it deserves.

07012, male, 37 years, usual care

The trial also helped usual-care arm participants understand that they were not alone with their TBI, despite not attending the memory rehabilitation groups as part of the intervention:

It’s [taking part in the trial] opened my eyes an awful lot, of how things are, and how I’ve got to accept my life is now and it’s not just me, there’s god knows how many out there are in the same position.

01005, male, 43 years, usual care

It [taking part in the trial] was good, it, it was informative, it helped me understand I’m not the only one with the problems.

01017, female, 30 years, usual care

Experience of assessments

Overall, participants were positive about the assessments that they undertook as part of the trial. The fact that they were conducted at home or at other convenient locations (e.g. local hospital) was highlighted as ideal in terms of travel arrangements and as a way of allowing participants to remain in their comfort zone. Additionally, participants found the assessments helpful with regard to highlighting their specific memory impairments and strengths:

The assessments have been done; it was either at [names location] when we were first looking at enrolling in the course, not exactly far to travel and then all the assessments and discussions afterwards have been here at the home – so that’s ideal for us.

03004, female, 39 years, intervention

Well my psychologist comes here [home] . . . I prefer it, it’s awful, it’s terrible . . . but this is my comfort zone . . . I feel better in my own home . . . I feel safe. I don’t know why, it’s weird isn’t it.

09018, female, 51 years, usual care

It was helpful that they [researchers] got back to me and showed me where the deficits were, with where I was lacking sort of thing.

03022, male, 25 years, usual care

However, one participant reported that she did not like the fact that the assessments highlighted her specific memory weaknesses:

I’m not sure if it [assessment] wasn’t useful but I didn’t really like the faces when she [researcher] showed me the faces [from an assessment] . . . which is probably because I needed more help with that, do you know what I mean? . . . But I knew that was a weakness and I don’t like weakness.

08007, female, 41 years, intervention

Although most participants were positive about the assessments, some felt that they were challenging and not necessarily reflective of real-life memory concerns. Additionally, one participant did not understand the need for repeated assessments throughout the trial:

I found it [the assessments] taxing in a way . . . some of the tests were OK, others because of problems with my memory and that was a bit taxing, do you know what I mean, but overall it was good to do, if that makes sense, yeah.

09018, female, 51 years, usual care

It’s [assessments] either focused on stuff I’m not very good at anyway, so like remembering names and faces, you’ve got so many faces and they all look similar and they all have like are relatively the same . . . they’re people I don’t really know or care about, I’m not going to remember them.

08002, male, 31 years usual care

You start thinking, why are you doing this [the assessment] . . . and then I had a reassessment and we had to do it all again which I thought was quite, well we’ve been here before haven’t we, do we need to do it again kind of thing.

03005, female, 56 years, intervention

Preference for rehabilitation format

The majority of participants stated that they would rather experience memory rehabilitation as part of a group than on a one-to-one basis, with the reason often being the benefit of sharing ideas with other participants who have first-hand knowledge of having a TBI.

In a group it’s much better cause then you can get the impact of someone else and they can give you an idea or vice versa so, erm but individual, no disrespect, but it’s like, yeah well I’m telling you all these things and you’ll try tell me, but they [group members] know what it’s like, but the actual person [AP] doesn’t.

01010, female, 24 years, intervention

It would probably be helpful to have a group-based thing . . . because one-on-one you don’t necessarily know what you, what you currently want help with . . . if you’re in a group you kind of hear other people’s struggles and you kind of come out and go ‘yeah, I have some problems with that’.

08002, male, 31 years, usual care

However, a few participants would have preferred one-to-one memory rehabilitation. They felt that one-to-one sessions would allow their relevant concerns to be addressed and enable them to discuss personal issues, as well as allowing them to concentrate more easily than in group situations:

One-to-one probably because I have had, I’ve been to other group sessions where I’ve found it’s not necessarily been very relevant which might sound a bit stupid . . . but I’ve definitely found, from my experiences, one-to-one sort of treatment and rehabs have been more useful. Because you can talk about your personal issues.

04008, female, 25 years, usual care

I would probably prefer one-to-one . . . I tell you why because in [rehabilitation centre] sometimes I cannot concentrate because there’s so much rambling, because there’s people with different levels of head injury, right, and some of them really ramble on and on and on and on and arrgghh! So sometimes I have to sit right at the back.

09018, female, 51 years, usual care

A few participants were unsure of their preference because they could see the benefits of both one-to-one and group rehabilitation formats.

I don’t know. I think you could cover the same things more tailored to individuals faster [in] one-to-one, but then obviously, you know, other patients . . . have got contributions to make that the person that’s running it [groups] don’t have, as well, and . . . it is quite nice to see other people with the same issues.

07002, female, 29 years, intervention

I think given my character I’m a very vivacious person I probably would have been good in a group but as you might have seen today I can go off on a tangent and I’m probably better with someone focusing on me . . . I don’t think a group would have been the wrong thing but better might have been I should try both.

07012, male, 37 years, usual care

Reaction to ‘usual-care’ allocation

Half of the participants randomised to the usual-care group stated that they had no problem with their allocation. This was often because of an understanding of the need for a control arm, although one participant expressed relief at not having to fit the weekly memory rehabilitation group sessions into his busy working schedule:

Which I don’t have a problem with [being in a control group] because I do understand the concept of how you need to have a baseline and I’d said that I was quite happy to participate in the study and, yes you’ve got to have willing baseline otherwise a study’s meaningless.

04010, male, 55 years, usual care

Kind of a bit relieved . . . a bit of me was worrying, thinking ‘how am I going to squeeze that [rehabilitation sessions] in with everything else?’

08002, male, 31 years, usual care

However, a few participants were disappointed with being allocated to the usual-care arm because they had hoped to receive the intervention, which they believed would improve their memory:

It would have been nice to have been in the other [i.e. treatment] group . . . Just to see what you were doing and if it worked and made a difference.

04008, female, 25 years, usual care

I was a little disappointed actually I was hoping that I might erm, experience something new that would help my memory.

04009, male, 46 years, usual care

A few participants misunderstood the randomisation process and believed that it was their performance on the baseline assessments that decided their allocation:

I didn’t really mind which, which group I’d, I‘d end up in er cause obviously we went through the various er questions and, that determine over time which group you went into.

03014, male, 27 years, usual care

It [the study test] was to see whether I’d be allocated into the, a group to go on to other tests or another different group, which obviously, which wouldn’t go on to the tests.

03022, male, 25 years, usual care

Overall impressions of the trial

When asked for their overall impressions of the trial, a few participants mentioned the personal characteristics of the trial staff:

All the assistants that have been involved in the study with me have been you know very easy going and explained everything to me.

03014, male, 37 years, usual care

I would like to say that erm all the people I’ve met and talked to have been very happy and very polite and very pleasant.

04009, male, 46 years, usual care

Overall, participants expressed satisfaction with taking part in the trial, but when asked specifically for suggestions for improvement they recommended that usual-care arm participants be sent the intervention manual at the end of the trial, a crossover study design (so that everyone received the intervention), a wider variety of assessments, more frequent assessments, more detailed feedback on assessments and a written timescale of key study dates (e.g. assessments):

Maybe the number maybe there could be more assessments, that would have been more helpful and give me a better idea between one and the next.

07012, male, 37 years, usual care

Timing of the intervention

Participants randomised to the memory rehabilitation group stated that they would have preferred to receive the memory rehabilitation sooner after their TBI, but ‘not too soon’ because of difficulty processing information immediately after their injury:

Yes, earlier would have been good . . . But not right at the beginning, because right at the beginning, it would have just gone in one ear and out the other, effectively.

07002, female, 29 years, intervention

Personally, from my point of view, it [memory rehabilitation] would have helped me if it was like 6–12 months after the accident rather than 4 years later.

03004, female, 39 years, intervention

Although participants in the usual-care arm were not asked specifically about the timing of memory rehabilitation, one usual-care arm participant’s feedback is valuable here. This participant felt that there was a need for memory rehabilitation at the optimal time after TBI. She described a lack of engagement with a neurorehabilitation centre in the year after her TBI:

They [clinical staff] were quite keen to do different courses and different things with me but at the time I was very reluctant, I just wasn’t in the right frame of mind I think, but had it been further down the line, because I was still quite unwell and not myself after the accident and I just wasn’t interested.

04008, female, 25 years, usual care

The extended length of time between participants’ TBI and the intervention meant that some participants found it challenging to adopt the new strategies being taught in the memory rehabilitation group:

So trying to learn, it’s like with a head injury and that you, you’re learning stuff like, it’s like you’re learning from new kind of thing, but trying to learn new strategies like, oh what was the one she [AP] said, like a dictaphone for instance, see that wouldn’t work for me, so I wouldn’t have tried it.

01010, female, 24 years, intervention

I’d muddled through and found strategies that worked for me and then to be thrown into a group, that’s the wrong term to use but to attend that group, and I’d be thrown 101 other strategies it’s like, hang on a minute I’m doing the, I’m using these strategies and it works for me and I can forget all those strategies and look at applying new ones and that takes effort and it takes energy and it takes thinking whereas had I not been going into a routine and using some of my own strategies I might have been a bit more susceptible to taking some of those on board.

03004, female, 39 years, intervention

This was linked to participants having already developed their own strategies. Almost half of the participants in the memory rehabilitation arm already knew some of the strategies taught in the memory rehabilitation group either because they had worked them out themselves or because they had attended other rehabilitation sessions:

Er yeah the, these strategies er, the strategies er I used most, I found at least half of them I use anyway.

01012, male, 59 years, intervention

I was doing quite a lot of it anyway from my own work but there were some extra tips that I picked up.

08007, female, 41 years, intervention

Format

The majority of participants described benefits gained from the group format of the memory rehabilitation. This included a feeling of not being alone with their TBI, sharing experiences with people in a similar situation, conversing with people who understand (as opposed to a lack of understanding outside the group), social interaction and sharing ideas or strategies:

We both [participant and other group member] found that talking to other people who’d had brain injury made you feel more normal, made you feel like it wasn’t just you.

05053, male, 32 years, intervention

the good thing about it [group] was the problems that the other people at the group were having which were the same as mine with the memory and everything, very, very similar.

06045, male, 56 years, intervention

I liked meeting others who’ve had brain injury and how they go about their day-to-day life and conversing really erm on how . . . other people you know in the, in the work, in their day-to-day life do not always understand you, maybe you’re a bit slower or a bit, you know.

03001, female, 54 years, intervention

The benefit of the group was to erm [pause] to realise that er, [pause] that, that I could get out and about and, and interact with these people socially.

01012, male, 59 years, intervention

It was really good to see us like, not only me giving ‘em ideas but them, them throwing ideas back at me, maybe that they haven’t tried yet.

01010, female, 24 years, intervention

Participants also commented on the composition of the group in relation to group attendance, the benefits of seeing other people with TBI looking well, feeling like a ‘fraud’ because of self-comparison of ability with the ability of those with more severe disabilities in the group, and conflicts within the group:

The other thing as I say, sadly er a, a couple of the guys erm didn’t turn up, I mean one was working . . . I just thought it was a shame that erm people didn’t turn up.

04005, male, 56 years, intervention

The hopes and dreams of these people [participants] have been er have been shattered you know, where, and er because of their circumstances but still they were, still they were happy within themselves and that to me was, that was important.

01012, male, 59 years, intervention

When you listen to the other people [participants] and especially two of the other people and you think oh my god it happened so long ago and they’re still really struggling. And it was really, it used to upset me, I felt like a fraud.

03005, female, 56 years, intervention

I’d had enough of it and I just said ‘will you shut up, you’re putting me off’ [to another group member] and it was like, even though everyone else was thinking it, I was the only one that had to say it but I thought no, it’s no use for me, you’re spoiling it [attending the group] for me, because I even thought of not going because the thought of seeing her [participant] again I thought oh, here we go.

05042, male, 51 years, intervention

Most participants were satisfied with the format of the memory rehabilitation group. However, the following suggestions were made when participants were specifically asked for ways that we could improve the intervention: more group sessions, longer sessions so that the information could be taught at a slower pace, the use of social events before and after the intervention, and a follow-up group to check the maintenance of memory strategy use:

Apart from being able to erm [pause] do the course for a longer period of time to be able to actually utilise things, [pause] but what I, what I want and what is really achievable, I don’t know if it’s feasible.

01015, male, 33 years, intervention

Instead of having I don’t know how many hours in a session I, I thought that if you could get an afternoon session, now maybe you classify it as too long, to go through things, I’d say a little bit slower.

04005, male, 56 years, intervention

I think the group was such a nice group I think we should be a good thing to organise like at the end of it was sit down and have a night out or go to the pub or something.

04002, male, 24 years, intervention

Well whether it was between the sessions or, erm if the sessions continues say, if they continued like, you know say you meet once every 3 months or once every, whatever and you, you met up with those people and you, and you know perhaps the lady [AP] or, or somebody from the memory place said you know have you, how’ve you been getting on with your er, your diaries, have you got all your diaries, have you been filling them out regularly.

03003, male, 55 years, intervention

Content of the manual

Almost half of the participants provided positive feedback on the content of the manual used in the memory rehabilitation groups. This included an appreciation of the group tasks, the belief that the structure of the sessions was good and stating that the language used in the manual was clear:

You have activities toward the end of each week, that’s good, because sometimes it is the practical experience of doing something that actually kind of consolidates the learning of it.

09008, male, 33 years, intervention

But I think the way it was set out was good, the way the leaflets – well, like a booklet explaining everything, which you followed where they explained what they were trying to do.

05042, male, 51 years, intervention

So the material was clear and concise and targeted so I don’t think er, I don’t think anything could be [improved].

01012, male, 59 years, intervention

However, one participant felt that the manual was written in a way that was difficult to understand:

I think there are elements of it which are written in PhD language.

09008, male, 33 years, intervention

In terms of negative feedback, a few participants stated that each session contained too much information. Additionally, one participant reported that the content was repetitive and another expressed a strong dislike for a particular relaxation exercise:

If I had to be really picky it was just that some of the sessions were very intense and there was a lot of information in that.

03004, female, 39 years, intervention

I think some of the stuff was repetitive. Because I’d never come across these sort of strategies they were using for improving memory, I found it a bit confusing, Some sort of overlapped with each other. I’m trying to think, what am I trying to do with it? It’s just like the last bit or something else.

05042, male, 51 years, intervention

There were certain points where it was – there was one page, I remember exactly what page it was, it really, it just pressed my button of ‘I don’t like this!’ It was page, I think it was 74, and it talked about relaxing . . . and I remember thinking I’m not going to relax. I’m not being told to relax. What made me totally not relax was being told to relax.

09008, male, 33 years, intervention

Group facilitator

Half of the participants spoke positively about the facilitators (APs) who led the memory rehabilitation groups. In particular, participants praised the facilitators’ knowledge, skill and positive personality traits:

[Facilitator] was very good and she listened too, we’d get into our own little debates and you know sort of, you sit there for a minute and she was very good at explaining things and she’d go over things at the beginning of the next session.

03005, female, 56 years, intervention

I thought [facilitator] was she was a nice person. I mean she was very, she was like, she obviously, you could tell she obviously cared by what she was doing it wasn’t just pay check. So that was nice.

04002, male, 24 years, intervention

However, one participant felt that the group facilitator treated him differently from the other group members. This was particularly in relation to how the facilitator was perceived to spend more time with, and give more attention to, some individuals than others:

He [other group member] could see there was a – I don’t want to say ‘favouritism’, but it was like – it was like he would get . . . 60% of attention, if you like. And the other one would get 30% and I’d get 10% [laughing]. It wasn’t equal.

09006, male, 53 years, intervention

Effects of the group

All participants reported positive effects of attending the memory rehabilitation group sessions. Besides the general positive comments [‘I found it all helpful’ (05053, male, 32 years, intervention)], participants commented on learning new strategies, the reinforcement of existing strategies, increased external strategy use, improvement in memory, increased understanding of how memory works, improvement in mood, increased confidence, reduced frustration/increased acceptance and contact with group members outside the group:

But now you guys have given me more techniques like how to use them, my phone, my laptop, my iPad, so erm and erm I’m erm my card in my wallet, just check and they’re all there and I texted me my card in my wallet.

04002, male, 24 years, intervention

I’m going to say reiterated, er what, what we’d found that we were doing the right things.

04005, male, 56 years, intervention

Memory wise, well I write a hell of a lot more down now so, I don’t forget half of much on that sense of things.

01015, male, 33 years, intervention

My wife says it [memory] has [improved], yes it has [pause and sighs] . . . I think it’s improved.

04005, male, 56 years, intervention

I suppose I’m more understanding, I’ve got more understanding of how brain injuries affect you, especially your memory, day-to-day things.

05042, male, 51 years, intervention

It’s given me confidence for a start to be able to travel outside of me little bubble, before it came to that point I never could quite get on a bus.

01015, male, 33 years, intervention

I mean it’s got better since I’ve been going to the group especially, has got better I’m not getting, I’m not getting as frustrated when people move things.

01010, female, 24 years, intervention

One of the girls there [name], I mean, we met a couple of times, yeah for coffee and it was nice, really nice.

03001, female, 54 years, intervention

However, two participants reported that the groups had a negative impact on their mood. One participant found it very upsetting to hear the other group members talk about their struggles with their TBI (see quote from participant 03005 under the format of the group subtheme), the other occasionally worried about her use of strategies:

It’s just err a reminder to be me to try and be, as you know, as more on the ball or more, more, but that gives me, that aches, how, how can I put it, that gives me a headaches when I worry or con-concern or not so concern, when I am thinking about that too much.

03001, female, 54 years, intervention

Learnt pre traumatic brain injury

A minority of participants reported developing memory rehabilitation strategies before their TBI as part of their employment:

Several years before the accident I’d done some, I’d learnt some memory techniques for use in work when, when I was a consultant, erm and for use around presentations so I’ve learnt like pegging and erm you know sort of weaving in a story.

03015, male, 36 years, usual care

Well a lot of the strategies I had . . . er a lot of the strategies [at the group] was stuff that er we used in the police . . . for er evidence gathering, erm investigations, etc., erm so a lot of the strategies I already knew but not with this context, if that makes sense.

04005, male, 56 years intervention

Self-generated strategies

Linked to the preceding subtheme, almost half of the participants had generated their own memory rehabilitation strategies. For some participants these were internal strategies, including name association and attempting to remember specific aspects of an event:

I mean I try to do association, so name association, erm, I’m, I’m terrible, I mean [name] I’ve got, but only because you’re, you’re here on your own, erm if there was two or three of you I probably wouldn’t get who was who.

04009, male, 46 years, usual care

I try and make something memorable happen . . . even if it’s talking to a new person and talking to them and erm, in that situation I think oh yeah I remember him, he had the bright yellow jacket on, I spoke to him, that was a day, it was a Thursday.

01017, female, 30 years, usual care

The majority of self-generated strategies were external memory aids. Writing things down was the most frequently used self-generated strategy, followed by inputting notes into a mobile phone. The use of a calendar, wall planner or a diary was the least frequently used strategy:

You find your own way of doing things and getting around and doing stuff, which for me is writing a lot of things down.

03004, female, 39 years, intervention

So I kind of always have my phone with me, so I’ve got lots of notes and things in there, written down.

07002, female, 29 years, intervention

Well, the main thing really is mainly with this, a calendar . . . Everything’s on there.

05042, male, 51 years, intervention

Yeah over the years I’ve found having a, a diary to hand, always, I can always keep track of my main events during the day.

03014, male, 37 years, usual care

Almost one-quarter of participants reported the use of other self-generated strategies. This was predominantly relying on routines, although one participant used word substitution and another used relaxation techniques:

I try and think, ok I’ll do things at certain times and put things, I try and put things in places which I usually forget to do but I try and look in certain places first and see if I’ve put it there.

04008, female, 28 years, usual care

If it happens in a sentence or something like that I can kind of er slide my way around it, the word that I can’t remember, so that people know what I’m talking about.

01003, male, 58 years, usual care

Almost one-quarter of participants specifically stated that they had had to generate their own strategies because of a lack of memory rehabilitation or support from other sources. For one participant this was cause for considerable distress:

I just give up and work it out myself. ’Cause I guess, in a way, I’m lucky in that I do – I’m, you know, clever enough or whatever to have that own resources to try and do that. So, yeah – so I know that I looked up things online and I got things from memory charities and stuff like booklets myself, to try to help myself . . . it would be better for them [doctors] to be giving me information, rather than not even telling me to go away, look it up and for me to have done something like this [intervention] group or – you know, just anything rather than just the feeling of, like – you know, as if it’s then your fault because it’s not been acknowledged that it’s actually an issue. [Crying]

07002, female, 29 years, intervention

I’ve done a lot of things just myself . . . I had to do a lot of recovery on my own.

01017, female, 30 years, usual care

This lack of memory rehabilitation or support is described further under the fourth theme, ‘usual care’.

Offered by other sources

Just under half of the participants had received advice or support on keeping a routine from other sources:

I have a routine, that’s another thing that I learnt in either the TBI team there and that or maybe is it [name of occupational therapist].

01010, female, 24 years, intervention

We [ABI team] did do some strategy stuff, sort of around making, er you know sort of substituting routine for memory if you like . . . making sure you always put things in the, in the same place and, and that sort of thing.

03015, male, 36 years, usual care

In terms of external memory strategies offered by other sources, writing things down was the most frequently used strategy, followed by the use of a calendar or diary:

That [inpatient rehabilitation] was one of the places that we, you know started to . . . say that it would be a good idea if you are not sure . . . where you want to go, what you want to wear or what you want to do, you know, write it down.

03001, female, 54 years, intervention

I put them all up there, like phone numbers and stuff like that on the calendar. I’ve got one next to me when I sit down if I’m in there. I write down on me calendar, like, ‘got to see me home Friday at 1 o’clock’, or whatever [suggested by the Brain Injury Trust].

05067, male, 53 years, usual care

She [from the TBI team] told me that it was the right thing to do, get a diary and that it would help.

01005, male, 43 years, usual care

Significance of strategies

A few participants felt an initial resistance to adopting memory strategies after their TBI. However, these participants did persevere with the strategies and were then able to experience the benefits:

I do remember my opinion at the time was I’ve never had a diary, don’t need a diary . . . I gave in and got one and now it’s got to the point, that, yeah again she was right, I was wrong cause I live by it.

01005, male, 43 years, usual care

I find them quite tedious and patronising and really you know, saying ‘Ohhh’, you know like sort of getting a pad out or whatever and writing things down and you know . . . But it does help.

03022, male, 25 years, usual care

Almost one-third of participants relied heavily on their strategies (particularly external memory strategies) in their daily activities:

I had to have an alarm to pick my children up from school, because otherwise I would forget.

07002, female, 29 years, intervention

I use, erm like my memory as my diary and my phone, this is like my lifeline, without them I’m you know, I’m just not, I, I’m useless.

01010, female, 24 years, intervention

Lack of memory rehabilitation

The level of memory rehabilitation received by the participants following their TBI varied greatly, with the majority reporting that they had received no memory rehabilitation at all external to the trial:

I do think that there is a massive gap in between there’s a massive gap I think for me I mean this is my personal experience after the accident hospital you’re discharged goodbye, good luck.

07012, male, 37 years, usual care

He [group member] got the care package, if you like, from day 1 . . . mine has been a DIY job . . . learning how to cope and – with not understanding other people – you know, people think you’re taking the mickey by forgetting to do that task or doing – you know, etcetera.

09006, male, 53 years, intervention

One participant felt that she did not receive memory rehabilitation because of performing adequately on memory tests shortly after her TBI, whereas, for her, her score represented a deterioration compared with before her injury:

So what I then found really difficult was they’re like, ‘Oh, well, you’re middle of the range on these tests. You’re fine’. And I’m like, ‘Yes, but I wouldn’t have been middle of the range so, actually, I’m not fine’ . . . And I think that I wasn’t able to articulate that at the time, because I wasn’t able to explain my thoughts properly then. So I think I just kind of got dismissed . . . I felt a huge amount of frustration and powerlessness, because I didn’t get any help, because I wasn’t able to explain that I needed it.

07002, female, 29 years, intervention

Perhaps not surprisingly, many participants stated that they wanted more support and rehabilitation to help with their memory:

It would be nice if there was access to errm memory techniques or a programme.

04010, male, 55 years, usual care

I would like more support, or – and certainly ideas and what I could do, not necessarily, well and probably also techniques of helping myself, but also stuff I could do to improve it [memory] as opposed to just working around, because I don’t want to just take notes all the time.

08002, male, 31 years, usual care

Memory rehabilitation received outside the trial

Almost half of the participants discussed the types of memory rehabilitation that they had accessed through sources other than the trial. The most common sources accessed were brain injury teams and neuropsychologists, with other sources including inpatient rehabilitation teams, charities, work, private companies and social workers:

The way I see it is what I’ve had with rehab and the TBI team and everything else they’ve, they’ve just been amazing.

01010, female, 24 years, intervention

Obviously I’ve gone through a few things with [neuropsychologist], and you know . . . sort of how, you know how I can help with writing things down and certain strategies.

03022, male, 25 years, usual care

Well when I was in hospital, when I was like an inpatient I think I did have erm I did have some memory but wasn’t very common.

04002, male, 24 years, intervention

That’s the Brain Injury Trust did that to me [suggested strategies], yeah.

05067, male, 53 years, usual care

I’ve had like coaching, like kind of business kind of coaching and various different things to try and put strategies in place so I, I’ll try anything.

03015, male, 36 years, usual care

I saw the rehab assistant from . . . July 2015 to December then got discharged officially in January this year, so the length of time that [private rehabilitation company] had been around for is a kind of, sort of, story of what . . . like cognitive rehab and all daily independent living.

09008, male, 33 years, intervention

Yeah, yeah, yeah, the social worker from the brain injury unit, I think she’s from [place], she was brilliant, she was good, she was very, very good . . . and she, you know, obviously because she works with the brain injury department, they knew a lot of the pitfalls of having this accident and a lot of the problems that you will have in the future, so she sort of pre-empted and tried to prevent a lot of them as well, which did work.

06045, male, 56 years, intervention

Other (non-memory) rehabilitation received

As could be expected, participants experienced a range of other health issues comorbid to their TBI for which they also attended rehabilitation. The most common ‘other’ rehabilitation was for mood issues and a few spoke about fatigue management groups and courses, physiotherapy and balance rehabilitation:

Well now they [Brain Injury Trust] come round and just check me mood swings because I used to get in bad moods and that like, but I’m not scared of nothing . . . they come round and check me pills and they put me on these anti-depressant pills even though I don’t feel depressed. But then they put me dose up and it has calmed me down a bit.

05067, male, 53 years, usual care

I’ve been to [place name, fatigue management group] and they showed me what happens because that’s why I sleep all the time.

05067, male, 53 years, usual care

But I got seen by the physios a bit longer than, than I should have done. I got seen by the intermediate community team longer than I should have been and they tried to have more of a smooth transition, that’s why they looked after me a bit longer, they wanted to just hand over as they see it, me being ready for life.

08002, male, 31 years, usual care

After my head injury yes, because I couldn’t balance, I lost my sense of balance . . . So through [neurological rehabilitation unit] . . . erm I was under the care of a couple of people there erm there was actually one who I can speak really highly of, [staff member], she put in place coping mechanisms.

04010, male, 55 years, usual care

Heterogeneity

As a pragmatic trial, our inclusion criteria were necessarily broad, which replicates how memory rehabilitation is delivered in clinical practice and contributes to the generalisability of the findings. However, this also meant that the sample was heterogeneous, but our trial was not designed to detect differences in the effect of the group memory rehabilitation (i.e. subgroup effects) according to baseline factors. Therefore, we intend to further analyse the data in this respect; the findings will provide us with some indications of which groups of people may benefit most from memory rehabilitation, and this would need to be tested out in future trials.

Generalisability

It was necessary to screen a large number of potential participants to recruit the required sample size, and a large proportion of those screened were not enrolled. This is largely because of the methods of recruitment used, which relied on postal invitations, which are known to suffer from poor response rates;137 indeed, non-response to the postal invitations accounted for 43% of people screened but not consented in the current trial. By comparison, only 28% of people were excluded on the grounds of eligibility, lending support to the representativeness of the current sample.

As a pragmatic trial, to reduce selection bias, we used multiple recruitment sources and strategies, including self-referrals. Unfortunately, this meant that we did not have demographic data on all those who were approached and invited or those who chose to self-refer as a result of the study publicity material. Furthermore, we were unable to collect this information at the recruitment stage because those interested had not given consent for us to collect these data for research purposes. Therefore, we cannot be certain whether or not there were differences between the characteristics of those who wanted to take part in the study and the characteristics of those who did not.

Research suggests that white, middle-class, highly educated men tend to be over-represented in health-care research in most Western countries. 138 Indeed, in our trial 96% of our sample identified as white. Surprisingly, the literature is sparse regarding racial and ethnic variations in the epidemiology of TBI in the UK. One older study,139 however, found substantial differences based on ethnic groups in relation to seasonal variations and differences in length of hospital stay following TBI. In relation to gender, typically men are over-represented by 3 : 1 in all subgroups of TBI. 140 Men formed more than two-thirds of our sample.

Comparability with other trials

Rather than reviewing individual studies, we have opted to compare our findings with those of published reviews. More men than women sustain brain injuries, with ratios estimated to be between 2 : 1 and 3 : 1. 141 This is consistent with our findings, with 73% of participants being male. In the Rohling et al. 13 systematic review of cognitive rehabilitation following ABI, the authors identified eight studies that considered rehabilitation of memory difficulties in TBI. In this review, the mean age of TBI participants was 29.1 years (SD 15.9 years), whereas our participants were older, with a mean age of 45.4 years (SD 12 years). The mean treatment duration was 13.3 weeks (SD 14.2 weeks), which is similar to our treatment duration of 10 weekly sessions.

The Cicerone et al. 25 review discusses the various treatment strategies covered in memory rehabilitation in ABI. Studies that they included in the review used internal memory aids (e.g. visual imagery techniques), memory retraining and external memory aids (e.g. diaries, pagers and other compensatory strategies). This suggests that the content of our intervention programme was comprehensive, elements of which have been investigated in other trials. Most of these trials suggested that participants benefited from using these strategies.

Fidelity of the intervention

It was a strength of the study that we were able to assess the fidelity of the intervention. The video analysis suggested that the therapists were delivering the intervention as planned and in accordance with the manual. However, the main limitation of the video analysis is that recordings were incomplete and did not include all sites. Some sessions were only partially recorded; recordings stopped partway through a session, probably because of the camera battery running low, or did not continue after the break, possibly because of the AP forgetting to turn the camera on again. Some recordings were lost and not transferred to the main site. This limited the recordings that could be included in the analysis and meant that not all sessions were observed at each site. Therefore, we cannot be certain that all sessions at all sites were delivered consistently in accordance with the manual. However, based on feedback obtained during our monthly peer and supervisor meetings with the APs, we do not expect that the unrecorded sessions were markedly different from the recorded ones.

Lack of an ‘active’ control arm

One of the challenges of conducting complex intervention trials, particularly in rehabilitation contexts, is having an ‘active’ control arm. In our pilot trial,23 we included an attention placebo self-help group as the control arm. In this group, participants met to discuss their health and memory problems and were taught relaxation exercises. The group facilitator did not initiate any memory talk. Our fidelity analysis of these sessions compared with the treatment sessions142 demonstrated that the self-help group underwent very little discussion around ‘memory’ and significantly less than in our treatment groups. However, our qualitative research24 suggested that even people in this self-help group were reporting some benefits of attending the sessions. Therefore, in the ReMemBrIn trial, we opted to have a treatment-as-usual control arm. However, based on the qualitative data (see Chapter 5, Usual care), it would appear that most people did not get much by way of usual care. This is a challenge that has been recognised in evaluating complex intervention and rehabilitation trials. 143

Methodological quality

The ReMemBrIn trial was a RCT. We took care to ensure allocation concealment and blinding of outcome assessors. Our SAP was agreed in advance of the data-lock stage. We have reported the trial in line with the Consolidated Standards of Reporting Trials (CONSORT) guidelines144 and the content, format and delivery of the intervention in line with the TIDieR131 and other relevant guidelines. 130 This should enable other researchers who wish to replicate this study to deliver the intervention as we have.

Sample size

Most previous studies of memory rehabilitation have been small and underpowered. This is an issue within the wider field of cognitive rehabilitation studies. The systematic review of Rohling et al. 13 identified RCTs of TBI with sample sizes ranging from 4 to 22. The ReMemBrIn trial was powered to detect a minimum clinically significant difference in mean EMQ-p score of 12 between the memory rehabilitation arm and the usual-care arm, taking into account between-site variations and clustering as a result of the intervention being delivered in a group. The target sample size of 312 was exceeded, with a total of 328 randomised participants, making this, to our knowledge, the largest trial of its kind to date.

Standardised manualised treatment

We were able standardise the treatment by having a manual and facilitator notes for facilitators at each site and a workbook for all participants in the memory rehabilitation arm. Facilitator training happened centrally, and monthly peer supervision and one-to-one supervision with one supervisor for all APs who delivered the intervention enabled sharing of experiences, which we hoped would encourage APs to adhere to the manual and facilitator notes. In the training programme and through supervision, we also taught the APs how they could adhere to the manual but also adapt the contents of each session to the needs of individuals within the group and the group as a whole.

Assessment of treatment fidelity

Our videos of the rehabilitation sessions from the various sites were coded and rated by two independent raters, which enabled us to determine the consistency of delivery of the intervention. There was some variation between sites, but part of this may have been because of variations in the sessions available for analysis between sites. Site 5 recordings were mainly from early sessions whereas recordings from sites 3, 8 and 9 were mainly from later sessions. This may account for the high proportion of time spent discussing the venue and organisational issues in the recordings from site 5 rather than discussing strategies. This site also included more facilitation of discussion, probably because this was needed more in the early sessions than in the later sessions.

Time sampling, in which behaviours are observed and recorded for a specific period of time,145 has been used mainly for ward-based observations of behavioural problems but we have found it useful to adapt this method to assess the ‘content fidelity’ of group-based rehabilitation interventions delivered in a research context with participants with neurological conditions. 142,146

Content fidelity has been defined as ‘the extent to which each intervention component was effectively delivered to the participants in terms of required content’. 147 The recording of activities indicated that appropriate content was covered. ‘Process fidelity’ was evident from the therapist skills observed, such as facilitating discussion, summarising and paraphrasing. However, process fidelity also involves the interpersonal skills of the therapist147 and there was no attempt to rate the quality of the interactions.

The fidelity to the intervention manual and consistency between therapists could have been improved if we had analysed the first group conducted by all APs and provided them with detailed feedback. This could then have been carried out routinely to ensure that there was no ‘drift’ in terms of intervention delivery for the rest of the trial. This of course has resource implications; therefore, in this trial, we analysed the video data only at the end of the trial.

In the delivery of complex interventions, we cannot be certain what the key ingredients are that would contribute to a positive outcome. In this study, we decided on the coding frame based on the activities and skills described in the manual. However, there may be other important aspects of the group sessions, such as group cohesiveness and therapist experience, which were not monitored.

Follow-up completion rates

Although 84% of the sample completed the assessment visit at the 6-month follow-up, only 75% and 78% of the participant questionnaires from the memory rehabilitation and usual-care arms, respectively, could be included in the primary analysis. This is slightly below our 80% response rate target; however, sensitivity analyses using multiple imputation to impute missing outcome data gave very similar results to the analysis using the available data.

Activity- and participation-level outcomes

Outcomes related to activity and participation levels of the ICF framework. 31 Frontera et al. ,143 in their summary of the Rehabilitation Research at the National Institutes of Health: Moving the Field Forward conference, stated that ‘In rehabilitation research, outcomes are often complex, occur across the domains of the International Classification of Function, and include patient-reported as well as performance-based and instrumented outcomes’. Many of the previous studies used impairment-level measures to assess the outcome of memory rehabilitation. Although impairment-level measures are useful in understanding the potential mechanisms that underlie changes effected by rehabilitation, as outcomes, they may not generalise to meaningful functional outcomes for patients. 148 Many of these impairment-level measures are ‘objective’ measures (i.e. based on cognitive tests). However, studies have also shown discrepancies between perceived and objective cognitive functioning,149,150 with subjective ratings being influenced by mood and self-efficacy. We acknowledge that the EMQ-p would have been influenced by these factors, but felt that it was the appropriate primary outcome because we expected participants who received the intervention to report a reduction in forgetting and improvements in coping with memory problems, which is in keeping with the spirit of cognitive rehabilitation. 70 Furthermore, we also included an objective measure of memory and relatives’ assessment of participants’ memory failures as secondary outcomes. Goal attainment was also a secondary outcome.

Another strength related to outcomes is that we assessed participants at both 6 and 12 months’ follow-up; therefore, in this study we were able to evaluate the longevity of the treatment effect, if any. Most previous studies have assessed outcomes only proximal to the end of the intervention.

Economic analysis

Past studies have considered only the clinical effectiveness of memory rehabilitation. To our knowledge, this is the first trial to have determined the cost of delivering memory rehabilitation and the cost-effectiveness of memory rehabilitation.