211 research outputs found
Null effects in trials – a worked example of a maltreatment prevention trial
No full textNull effects in trials occur when there is insufficient difference between the intervention and control arms for tested primary outcomes to reject the null hypothesis. In this chapter, the authors explore the prevalence of null effects in different domains where clinical trials have been undertaken. Using a case study trial of specialist home visiting intended to prevent maltreatment, they explore what may contribute to null effects in trials. Such null effects include occasions where differences in effect are found between early stages of research, where the potential efficacy of a new approach shows promise, and later phases where interventions may be delivered at scale. The authors look at what may be learnt from trials where a null effect is concluded for both future design and delivery of a new intervention or service and for future evaluation
Meta-research to improve the planning and reporting of randomized clinical trials
No full textThe ongoing challenge of poor research persists in the scientific community, highlighting concerns about unreliable findings, misguiding decision-making processes, and losing public trust. A key solution lies in addressing the burden of inadequate methods by making adjustments. Better planning and reporting are essential to tackle this issue effectively. Meta-research, involving interdisciplinary research on research methods, offers insights into existing challenges. In this PhD, we proposed two main meta-research projects to identify problems and suggest solutions, ultimately improving the planning, and reporting of randomized controlled trials (RCTs): i) The pattern of RECRUITment In randomized clinical trials (RECRUIT-IT) study, and ii) Subprojects of the ASPIRE (Adherence to SPIRIT Recommendations) Study on different methodological topics.
i) RECRUIT-IT study:
We conducted an empirical study using individual participant recruitment data from RCTs, gathered from convenient national, and international networks, to empirically identify common trial recruitment patterns. Our findings indicate that approximately two-thirds of RCTs had an overall linear recruitment trajectory, facilitating straightforward predictions of future recruitment. Principal investigator (PI) sites generally contributed more, longer, and faster in participant recruitment, underscoring their crucial role in ensuring successful trial conduct.
ii) Subprojects of the ASPIRE study:
Our team has built a database of 760 RCT protocols already approved by research ethics committees in Switzerland (Basel, Bellinzona, Bern, Geneva, Lausanne, St. Gallen, Thurgau, Zurich), Germany (Freiburg), Canada (Hamilton), and UK; 360 RCT protocols from 2012 and 400 from 2016. We used this database and complemented it with additional information from RCT protocols and corresponding publications to provide empirical evidence on A) non-registration, discontinuation, and non-publication of RCTs, B) the prevalence and reporting of patient reported outcomes (PROs) in RCT protocols and publications, and C) reporting of prespecified subgroup analyses in RCT protocols. The results of subproject A showed that non-registration (6%), and non-availability of results (20%) remain significant issues, with non-industry trials being more affected than industry trials. Additionally, approximately one third of all RCTs were prematurely discontinued, mainly due to poor participant recruitment. The results of subproject B showed that 70% of RCTs specified PROs as either primary or secondary outcomes, with significant variability among medical disciplines and interventions. The reporting standard for PROs in both protocols and publications was suboptimal, with a considerable proportion failing to adhere to protocol specifications when reporting PRO results. Similarly, the results of subproject C showed that planned subgroup analyses in the majority of RCT protocols were remained persistently inadequately in addressing fundamental scientific principles such as prior research considerations, limiting the number of subgroup analyses, and applying appropriate statistical methods.
The insights from the RECRUIT-IT study provide investigators with an overview of common trial recruitment patterns on the trial-level and the site-level, facilitating prediction and monitoring of participant recruitment in RCTs. Consequently, they can intervene to improve recruitment if it is needed, reducing the risk of unsuccessful recruitment and trial discontinuation. Assuring recruitment preserves research integrity by allowing the study to progress as intended, thereby minimizing the chance of discontinuation and research waste.
Insights from ASPIRE subprojects have raised awareness and highlighted the importance of various methodological challenges in trial registration, results publication, and planning and reporting of PROs and subgroup analyses. Enhancing registration and publication practices can reduce duplication, publication bias, and enhance transparency, thus reducing research waste. Simultaneously, effective planning and adherence to PRO protocols and improving methodological quality in subgroup analysis have a crucial role in ensuring the credibility of RCT results, aiding in waste reduction, and promoting more robust and transparent clinical research.
Delivering early care in diabetes evaluation (DECIDE): a protocol for a randomised controlled trial to assess hospital versus home management at diagnosis in childhood diabetes
No full textBackground: There is increased incidence of new cases of type 1 diabetes in children younger than 15 years. The debate concerning where best to manage newly diagnosed children continues. Some units routinely admit children to hospital whilst others routinely manage children at home. A Cochrane review identified the need for a large well-designed randomised controlled trial to investigate any significant differences in comprehensive short and long-term outcomes between the two approaches. The DECIDE study will address these knowledge gaps, providing high quality evidence to inform national and international policy and practice.Methods/Design: This is a multi-centre randomised controlled trial across eight UK paediatric diabetes centres. The study aims to recruit 240 children newly diagnosed with type 1 diabetes and their parents/carers. Eligible patients (aged 0-17 years) will be remotely randomised to either 'hospital' or 'home' management. Parents/carers of patients will also be recruited. Nursing management of participants and data collection will be co-ordinated by a project nurse at each centre. Data will be collected for 24 months after diagnosis; at follow up appointments at 3, 12 and 24 months and every 3-4 months at routine clinic visits.The primary outcome measure is patients' glycosylated haemoglobin (HbA1c) at 24 months after diagnosis. Additional measurements of HbA1c will be made at diagnosis and 3 and 12 months later. HbA1c concentrations will be analysed at a central laboratory.Secondary outcome measures include length of stay at diagnosis, growth, adverse events, quality of life, anxiety, coping with diabetes, diabetes knowledge, home/clinic visits, self-care activity, satisfaction and time off school/work. Questionnaires will be sent to participants at 1, 12 and 24 months and will include a questionnaire, developed and validated to measure impact of the diagnosis on social activity and independence. Additional qualitative outcome measures include the experience of both approaches by a subgroup of participants (n = 30) and health professionals. Total health service costs will be evaluated. A cost effectiveness analysis will assess direct and indirect health service costs against the primary outcome (HbA1c).Discussion: This will be the first randomised controlled trial to evaluate hospital and home management of children newly diagnosed with type 1 diabetes and the findings should provide important evidence to inform practice and national guidelines.Trial registration numberISRCTN: ISRCTN78114042<br/
Correspondence: Questioning the outcome of the Building Blocks trial
No full textMichael Robling and colleagues (Oct 13, p 146) are to be congratulated on conducting Building Blocks, a highly rigorous randomised controlled trial of the Family Nurse Partnership (FNP) programme in England, UK, and rightly highlighted the difficulty in showing changes similar to the US studies in a setting with comprehensive universal health services. The trial in the Netherlands, where FNP showed a positive effect on various primary outcomes, involved substantial adaptation of the programme to the local context, and was also more targeted in terms of risk
2003/04 Indiana University School of Law Faculty
No full textRow 1: Susan Williams, Robert Fischman, John Applegate, Michael Grossberg, Kevin Brown, Daniel Conkle, Sarah Jane Hughes, Marshall Leaffer, Lauren Robel, John Scanlan Row 2: Gene Shreve, James Barnes, Sophia Goodman, Nona Watt, Jennifer Bryan Morgan, Aviva Orenstein, Linda Fariss, Amy Applegate, Ajay Mehrotra, William Henderson Row 3: Kenneth Dau-Schmidt, Kevin Robling, Elizabeth Goldberg, Dawn Johnsen, Christina Ochoa, Jost Delbrück, Mike Maben, Jeannine Bell, Lesley Davis, Lisa Farnsworth, Elizabeth Hodges, David Williams Row 4: Ralph Gaebler, Michael Jenuwine, Luis Fuentes-Rohwer, Joseph Hoffmann, Hannah Buxbaum, Charles Geyh, Fred Aman, Bill Hicks, Donald Gjerdigen, Cynthia Reichard, Lara Daghe, Peter Hook Row 5: Roger Dworkin, Jeff Stake, Paul Craig, Fred Cate, David Snyder, Craig Bradley, Alex Tanford, Seth Lahn, Mark Hilycordhttps://www.repository.law.indiana.edu/facgrp/1024/thumbnail.jp
Measuring change in patient quality of life over time : an evaluation of scale responsiveness and patient response shift.
No full textMeasuring change in quality of life is increasingly central to health services and clinical research evaluation. This requires instruments that are responsive to change, and that the construct being assessed is stable. I have, therefore, addressed two methodological themes: scale responsiveness and instability of the underlying quality of life construct - response shift. Responsiveness theme: I evaluated performance characteristics of a commonly reported effect size statistic, the standardised response mean (SRM). Computer simulations modelled the impact of varying computational method and distributional characteristics upon bias of estimated effect size compared to underlying true value. The studies provide evidence and reassurance that the SRM exhibits little bias when sample size, mean underlying effect size and shape of underlying distribution are varied. However, alternate approaches to handling negative values can produce markedly different effect sizes, making comparison across studies that use different methods problematic. Furthermore, parametric SRMs calculated from lognormal data may provide a greatly inflated estimate of effect size. Response shift theme: I interviewed patients at different stages of clinical management for knee injury twice over six months. A multi-method approach incorporating the individualised SEIQoL-DW measure and a retrospective pretest-posttest using EQ-5D identified evidence of re-calibration, re-prioritisation and re-conceptualisation response shift. An empirically based typology of changes was developed drawn from existing response shift theory, but which further distinguishes subtler forms of change. The studies provide evidence that re-prioritisation and re-conceptualisation may be different levels of the same process. Furthermore, mechanisms producing response shift were identified, in particular, the interaction between level of satisfaction with quality of life domain and its perceived importance. Additional approaches to studying response shift using group level comparison of SEIQoL data were critically evaluated. The thesis extends the methods for identifying, assessing and conceptualising response shift changes whilst also exploring mechanisms which may explain these changes
2003/04 Indiana University School of Law Faculty
No full textRow 1: Susan Williams, Robert Fischman, John Applegate, Michael Grossberg, Kevin Brown, Daniel Conkle, Sarah Jane Hughes, Marshall Leaffer, Lauren Robel, John Scanlan Row 2: Gene Shreve, James Barnes, Sophia Goodman, Nona Watt, Jennifer Bryan Morgan, Aviva Orenstein, Linda Fariss, Amy Applegate, Ajay Mehrotra, William Henderson Row 3: Kenneth Dau-Schmidt, Kevin Robling, Elizabeth Goldberg, Dawn Johnsen, Christina Ochoa, Jost Delbrück, Mike Maben, Jeannine Bell, Lesley Davis, Lisa Farnsworth, Elizabeth Hodges, David Williams Row 4: Ralph Gaebler, Michael Jenuwine, Luis Fuentes-Rohwer, Joseph Hoffmann, Hannah Buxbaum, Charles Geyh, Fred Aman, Bill Hicks, Donald Gjerdigen, Cynthia Reichard, Lara Daghe, Peter Hook Row 5: Roger Dworkin, Jeff Stake, Paul Craig, Fred Cate, David Snyder, Craig Bradley, Alex Tanford, Seth Lahn, Mark Hilycordhttps://www.repository.law.indiana.edu/facgrp/1024/thumbnail.jp
Spinal function classification framework for non-specific low back pain: a delphi survey of academic experts and clinicians
No full textIntroduction: Low back pain (LBP) and sciatica guidelines encourage people to remain physically active to better self-manage their condition1. This may prove challenging for LBP patients who operate with demonstrable physical aberrations, including reduced range of motion, poor muscle function, reduced sense of balance, are generally physically deconditioned with low exercise tolerance levels. Clinical assessment of spinal function is a routine part of (LBP) assessment, yet there is no clear consensus on what constitutes of a ‘spinal dysfunction’ and how this informs treatment.
Purpose: To develop LBP physical function assessment and exercise performance framework by gaining expert academic and clinical consensus for:(i) spinal physical function assessment tests, (ii) spinal physical function LBP subsets and their characteristics, (iii) exercises recommended for each LBP subset.
Methods: Wed-based 2-round Delphi survey method was used to build an academic expert and clinical consensus. 92 individuals were surveyed. In round 1 world-leading academic experts participating in round 1 (n=5) rated their agreement and elaborated on items generated from literature on spinal assessment tests, LBP subsets, their characteristics and exercises recommended for each LBP subset. In round 2, 87 clinical physiotherapy specialists (extended scope practitioners) were asked to rate their agreement with round 1 generated items on the assessment tests, LBP subsets & their characteristics and exercise items and its performance in each LBP subset. A five-point Likert scale was used to obtain level of agreement (LOA). A priori consensus was set at 80% LOA.
Results: Forty participants responded (44%) (U.K., Norway, Belgium, Ireland, Italy, Brazil, Japan) with 4 academic experts (round 1) and 36 clinical physiotherapy experts (round 2). From 174 in round 1, 85 items gained >80% agreement. Five (out of 14) spinal physical function assessment tests were considered ‘very important, important’ reaching =/>80% agreement. Out of ten proposed LBP physical function subsets, 7 were recognised by clinicians reaching required level of agreement (=/>80%LOA). Out of 128 described characteristics within the 7 physical function LBP subsets, 12 reached consensus (=/>80%LOA). Seven out of 12 exercises were considered ‘very important / important’ with highest agreement on exercises re-training sitting, standing, forward bend and sit-to-stand. LBP subset specific exercise performance was mapped with 26 items (out of 34) on compensations and 28 items (out of 52) on exercise feedback gaining consensus (=/>80%LOA).
Conclusion: First to date study gaining academic and clinical expert consensus on spinal function assessment and exercise performance for LBP. The consensus within the studied domains was comparable across academic and clinical experts. Mapping spinal physical function and exercise performance across clinically recognised subsets of LBP could be used to develop technologies to better equip and guide LBP patients through the exercise component of their self-managemen
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