68 research outputs found
Physiotherapy for Patients with Sciatica Awaiting Lumbar Micro-discectomy Surgery: A Nested, Qualitative Study of Patients' Views and Experiences
Background and Purpose
Sciatica is a common clinical condition that can be extremely painful, disabling and lifeâchanging. Whether conservative or surgical treatment for sciatica secondary to an intervertebral disc prolapse is most effective is still much debated. An important component of conservative treatment is physiotherapy, which aims to promote physical and psychological health for the patient, whilst resorption of the disc takes place. This paper reports a qualitative study of patients' views and experiences of a bespoke physiotherapy intervention for the treatment of sciatica.
Methods
A qualitative study nested within a pilot randomized controlled trial of bespoke physiotherapy for the treatment of patients with sciatica awaiting lumbar microdiscectomy surgery. Patients randomized to receive bespoke physiotherapy in the intervention arm of the trial were invited to take part in semiâstructured interviews. Twentyâone inâdepth, semiâstructured interviews took place. All interviews were recorded, fully transcribed and thematically analysed.
Results
Most patients in the sample found the physiotherapy valuable, appreciating the individual nature of the approach, the exercises to reduce pain and discomfort, techniques for improving functional spinal movement, walking and dynamic posture, and manual therapy and cardiovascular exercise. A small number did not find the physiotherapy of benefit. Sixteen patients in the sample went on to proceed with surgery, but most of these found value in having had the physiotherapy first.
Discussion
Many patients with sciatica appreciate the value of physiotherapy prior to surgery. Future research should examine patients' experiences of bespoke physiotherapy delivered within primary care
Reporting issues in group sequential randomised controlled trials: a systematic review protocol of published journal reports
Background: Adaptive designs are somewhat underused, despite prominence given to methodology in the statistical literature. Some concerns relates to robustness of adaptive designs in decision making, acceptability of trial findings to change practice, anxiety about early stopping of trials and worry about wrong decision making. These issues could be linked to inadequate reporting of the conduct of such clinical trials. We assess the reporting of group sequential randomised controlled trials (RCTs), which are one of the most well-understood adaptive designs in the confirmatory setting.
Methods: We undertake a systematic review searching Ovid MEDLINE from 1st January 2001 to 23rd September 2014 and including parallel group confirmatory group sequential RCTs that were prospectively designed using the Frequentist approach. Eligible trials are screened for completeness in reporting against the CONSORT 2010 checklist with some proposed modifications to capture issues such as statistical bias correction following early stopping. Descriptive statistics aided with forest plots on CONSORT compliance are presented.
Discussion: Reporting of the conduct of adaptive designs is an area which has not been fully explored. Hence, the findings from this study can enlighten us on the adequacy in reporting of well-understood group sequential RCTs as a class of adaptive designs and on ways to address some of the cited concerns. Most importantly, the study can inform policy makers on the adequacy of the current CONSORT statements in enhancing reporting of such adaptive designs
Meandering journey towards routine trial adaptation: survey results on barriers to use of adaptive designs in confirmatory trials
Delphi consensus reached to produce a decision tool for SelecTing Approaches forRapid Reviews (STARR)
OBJECTIVES:
There are many rapid review methods; however, there is little pragmatic guidance on which methods to select. This study aimed to reach consensus among international rapid review experts outlining areas to consider when selecting approaches for rapid reviews.
STUDY DESIGN AND SETTING:
A two-round modified online Delphi survey was conducted between May and July 2018. Participants were asked to rank the importance of a predefined list of 19 items. A consensus definition of at least 70% agreement for each item was decided a priori.
RESULTS:
Thirty experts from ten countries participated in Round 1 and 24 in Round 2. During Round 1, consensus was reached on all items. One additional item on quality assessment was suggested by respondents and comments suggested wording changes to improve clarity and understanding of the tool. Respondents in the second round indicated a high level of importance and all 20 items achieved consensus. These items addressed interaction with commissioners, scoping and searching the evidence-base, data extraction and synthesis methods, and reporting of rapid review methods.
CONCLUSIONS:
International consensus was reached to produce the STARR decision tool for planning rapid reviews and will lead to improved shared understanding between review teams and review commissioners
Point estimation for adaptive trial designs II: practical considerations and guidance
In adaptive clinical trials, the conventional end-of-trial point estimate of a treatment effect is prone to bias, that is, a systematic tendency to deviate from its true value. As stated in recent FDA guidance on adaptive designs, it is desirable to report estimates of treatment effects that reduce or remove this bias. However, it may be unclear which of the available estimators are preferable, and their use remains rare in practice. This article is the second in a two-part series that studies the issue of bias in point estimation for adaptive trials. Part I provided a methodological review of approaches to remove or reduce the potential bias in point estimation for adaptive designs. In part II, we discuss how bias can affect standard estimators and assess the negative impact this can have. We review current practice for reporting point estimates and illustrate the computation of different estimators using a real adaptive trial example (including code), which we use as a basis for a simulation study. We show that while on average the values of these estimators can be similar, for a particular trial realization they can give noticeably different values for the estimated treatment effect. Finally, we propose guidelines for researchers around the choice of estimators and the reporting of estimates following an adaptive design. The issue of bias should be considered throughout the whole lifecycle of an adaptive design, with the estimation strategy prespecified in the statistical analysis plan. When available, unbiased or bias-reduced estimates are to be preferred
Non-randomised studies should be considered for assessing surgical techniques in rectal prolapse : prospective cohort study
Objectives
Randomised trials comparing surgical techniques for rectal prolapse are not always feasible. We assessed whether nonârandomised comparisons of those who have had surgery with those still waiting would be confounded baseline health status.
Study Design and Setting
Prospective cohort study in seven UK hospitals. Participants â„18 years listed for surgical interventions of equivalent intensity for rectal prolapse. Participants were defined as short or long waiters (†or >18 weeks, respectively). Time on the waiting list was compared with baseline comorbidity (Charlson Comorbidity Index, CCI) and change from baseline in health status (EQâ5Dâ5L) at the time of surgery.
Results
203 patients were analysed. Median (IQR) waiting time was 13.7 weeks (8.1, 20.4) varying across sites. Baseline comorbidity was not an important predictor of waiting time. Median CCI was 2 (0, 3) for short and 1 (0, 3) for long waiters. A change in waiting time by a week was associated with negligible improvement in EQâ5Dâ5L index of 0.001 (95%CI: â0.000 to 0.003, p =0.106).
Conclusion
Negligible change in patient reported health status while on waiting list and lack of effect of comorbidities in influencing waiting time supports the use of nonârandomised preâ/postâstudy to compare the effects of surgical interventions for rectal prolapse
Computerised speech and language therapy or attention control added to usual care for people with long-term post-stroke aphasia : the Big CACTUS three-arm RCT
Background: People with aphasia may improve their communication with speech and language therapy
many months/years after stroke. However, NHS speech and language therapy reduces in availability over time post stroke.
Objective: This trial evaluated the clinical effectiveness and cost-effectiveness of self-managed computerised speech and language therapy to provide additional therapy.
Design: A pragmatic, superiority, single-blind, parallel-group, individually randomised (stratified block randomisation, stratified by word-finding severity and site) adjunct trial.
Setting: Twenty-one UK NHS speech and language therapy departments.
Participants: People with post-stroke aphasia (diagnosed by a speech and language therapist) with long-standing (> 4 months) word-finding difficulties.
Interventions: The groups were (1) usual care; (2) daily self-managed computerised word-finding therapy tailored by speech and language therapists and supported by volunteers/speech and language therapy assistants for 6 months plus usual care (computerised speech and language therapy); and (3) activity/attention control (completion of puzzles and receipt of telephone calls from a researcher for 6 months) plus usual care.
Main outcome measures: Co-primary outcomes â change in ability to find treated words of personal relevance in a bespoke naming test (impairment) and change in functional communication in conversation rated on the activity scale of the Therapy Outcome Measures (activity) 6 months after randomisation. A key secondary outcome was participant-rated perception of communication and quality of life using the
Communication Outcomes After Stroke questionnaire at 6 months. Outcomes were assessed by speech and language therapists using standardised procedures. Cost-effectiveness was estimated using treatment costs and an accessible EuroQol-5 Dimensions, five-level version, measuring quality-adjusted life-years.
Results: A total of 818 patients were assessed for eligibility and 278 participants were randomised between October 2014 and August 2016. A total of 240 participants (86 usual care, 83 computerised speech and language therapy, 71 attention control) contributed to modified intention-to-treat analysis at
6 months. The mean improvements in word-finding were 1.1% (standard deviation 11.2%) for usual care, 16.4% (standard deviation 15.3%) for computerised speech and language therapy and 2.4% (standard deviation 8.8%) for attention control. Computerised speech and language therapy improved word-finding 16.2% more than usual care did (95% confidence interval 12.7% to 19.6%; p < 0.0001) and 14.4% more than attention control did (95% confidence interval 10.8% to 18.1%). Most of this effect was maintained at 12 months (n = 219); the mean differences in change in word-finding score were 12.7%
(95% confidence interval 8.7% to 16.7%) higher in the computerised speech and language therapy group (n = 74) than in the usual-care group (n = 84) and 9.3% (95% confidence interval 4.8% to 13.7%) higher in the computerised speech and language therapy group than in the attention control group (n = 61). Computerised speech and language therapy did not show significant improvements on the Therapy Outcome Measures or Communication Outcomes After Stroke scale compared with usual care or attention control. Primary cost-effectiveness analysis estimated an incremental cost per participant of
ÂŁ732.73 (95% credible interval ÂŁ674.23 to ÂŁ798.05). The incremental quality-adjusted life-year gain was 0.017 for computerised speech and language therapy compared with usual care, but its direction was uncertain (95% credible interval â0.05 to 0.10), resulting in an incremental cost-effectiveness ratio of ÂŁ42,686 per quality-adjusted life-year gained. For mild and moderate word-finding difficulty subgroups, incremental cost-effectiveness ratios were ÂŁ22,371 and ÂŁ28,898 per quality-adjusted life-year gained, respectively, for computerised speech and language therapy compared with usual care.
Limitations: This trial excluded non-English-language speakers, the accessible EuroQol-5 Dimensions,
five-level version, was not validated and the measurement of attention control fidelity was limited.
Conclusions: Computerised speech and language therapy enabled additional self-managed speech
and language therapy, contributing to significant improvement in finding personally relevant words
(as specifically targeted by computerised speech and language therapy) long term post stroke. Gains
did not lead to improvements in conversation or quality of life. Cost-effectiveness is uncertain owing
to uncertainty around the quality-adjusted life-year gain, but computerised speech and language
therapy may be more cost-effective for participants with mild and moderate word-finding difficulties.
Exploring ways of helping people with aphasia to use new words in functional communication contexts
is a priority.
Trial registration: Current Controlled Trials ISRCTN68798818
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An Investigation of the Shortcomings of the CONSORT 2010 Statement for the Reporting of Group Sequential Randomised Controlled Trials: A Methodological Systematic Review.
BACKGROUND: It can be argued that adaptive designs are underused in clinical research. We have explored concerns related to inadequate reporting of such trials, which may influence their uptake. Through a careful examination of the literature, we evaluated the standards of reporting of group sequential (GS) randomised controlled trials, one form of a confirmatory adaptive design.
METHODS: We undertook a systematic review, by searching Ovid MEDLINE from the 1st January 2001 to 23rd September 2014, supplemented with trials from an audit study. We included parallel group, confirmatory, GS trials that were prospectively designed using a Frequentist approach. Eligible trials were examined for compliance in their reporting against the CONSORT 2010 checklist. In addition, as part of our evaluation, we developed a supplementary checklist to explicitly capture group sequential specific reporting aspects, and investigated how these are currently being reported.
RESULTS: Of the 284 screened trials, 68(24%) were eligible. Most trials were published in "high impact" peer-reviewed journals. Examination of trials established that 46(68%) were stopped early, predominantly either for futility or efficacy. Suboptimal reporting compliance was found in general items relating to: access to full trials protocols; methods to generate randomisation list(s); details of randomisation concealment, and its implementation. Benchmarking against the supplementary checklist, GS aspects were largely inadequately reported. Only 3(7%) trials which stopped early reported use of statistical bias correction. Moreover, 52(76%) trials failed to disclose methods used to minimise the risk of operational bias, due to the knowledge or leakage of interim results. Occurrence of changes to trial methods and outcomes could not be determined in most trials, due to inaccessible protocols and amendments.
DISCUSSION AND CONCLUSIONS: There are issues with the reporting of GS trials, particularly those specific to the conduct of interim analyses. Suboptimal reporting of bias correction methods could potentially imply most GS trials stopping early are giving biased results of treatment effects. As a result, research consumers may question credibility of findings to change practice when trials are stopped early. These issues could be alleviated through a CONSORT extension. Assurance of scientific rigour through transparent adequate reporting is paramount to the credibility of findings from adaptive trials. Our systematic literature search was restricted to one database due to resource constraints
SPIRIT and CONSORT extensions for early phase dose-finding clinical trials:the DEFINE (DosE FIndiNg Extensions) study protocol
Introduction Early phase dose-finding (EPDF) studies are critical for the development of new treatments, directly influencing whether compounds or interventions can be investigated in further trials to confirm their safety and efficacy. There exists guidance for clinical trial protocols and reporting of completed trials in the Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) 2013 and CONsolidated Standards Of Reporting Randomised Trials (CONSORT) 2010 statements. However, neither the original statements nor their extensions adequately cover the specific features of EPDF trials. The DEFINE (DosE-FIndiNg Extensions) study aims to enhance transparency, completeness, reproducibility and interpretation of EPDF trial protocols (SPIRIT-DEFINE) and their reports once completed (CONSORT-DEFINE), across all disease areas, building on the original SPIRIT 2013 and CONSORT 2010 statements.
Methods and analysis A methodological review of published EPDF trials will be conducted to identify features and deficiencies in reporting and inform the initial generation of the candidate items. The early draft checklists will be enriched through a review of published and grey literature, real-world examples analysis, citation and reference searches and consultation with international experts, including regulators and journal editors. Development of CONSORT-DEFINE commenced in March 2021, followed by SPIRIT-DEFINE from January 2022. A modified Delphi process, involving worldwide, multidisciplinary and cross-sector key stakeholders, will be run to refine the checklists. An international consensus meeting in autumn 2022 will finalise the list of items to be included in both guidance extensions.
Ethics and dissemination This project was approved by ICRâs Committee for Clinical Research. The Health Research Authority confirmed Research Ethics Approval is not required. The dissemination strategy aims to maximise guideline awareness and uptake, including but not limited to dissemination in stakeholder meetings, conferences, peer-reviewed publications and on the EQUATOR Network and DEFINE study websites
Exploring the barriers to, and importance of, participant diversity in early-phase clinical trials: an interview-based qualitative study of professionals and patient and public representatives
Objectives
To explore the importance of, and barriers to achieving, diversity in early-phase clinical trials.
Design
Qualitative interviews analysed using thematic analysis.
Setting and participants
Five professionals (clinical researchers and methodologists) and three patient and public representatives (those with experience of early-phase clinical trials and/or those from ethnic minority backgrounds) were interviewed between June and August 2022. Participants were identified via their institutional web page, existing contacts or social media (eg, X, formerly known as Twitter).
Results
Professionals viewed that diversity is not currently considered in all early-phase clinical trials but felt that it should always be taken into account. Such trials are primarily undertaken at a small number of centres, thus limiting the populations they can access. Referrals from clinicians based in the community may increase diversity; however, those referred are often not from underserved groups. Referrals may be hindered by the extra resources required to approach and recruit underserved groups and participants often having to undertake âself-drivenâ referrals. Patient and public representatives stated that diversity is important in research staff and that potential participants should be informed of the need for diversity. Those from underserved groups may require clarification regarding the potential harms of a treatment, even if these are unknown. Education may improve awareness and perception of early-phase clinical trials. We provide 14 recommendations to improve diversity in early-phase clinical trials.
Conclusions
Diversity should be considered in all early-phase trials. Consideration is required regarding the extent of diversity and how it is addressed. The increased resources needed to recruit those from underserved groups may warrant funders to increase the funds to support the recruitment of such participants. The potential harms and societal benefits of the research should be presented to potential participants in a balanced but accurate way to increase transparency
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