PhD / Abstract Low back pain is a significant public health problem in many countries of the world being one of the major causes of work absence and disability. Although the outlook for evidence-based management of low back pain has greatly improved over the past decades, many questions remain. Questions related to treatment options, underlying mechanisms of treatment effects and optimal assessment of low back pain have yet to be fully addressed by researchers. The broad aim of this thesis therefore was to contribute to a better understanding of the contemporary management of low back pain by performing studies in these key research areas. Most clinical practice guidelines recommend exercise as an effective treatment option for chronic low back pain. However the evidence for this recommendation comes from trials that are not placebo-controlled and so this may potentially provide biased estimates of the effects of exercise. Therefore a randomised controlled trial testing the effect of motor control exercise versus placebo in patients with chronic low back pain was conducted. Chapters 2 and 3 describe the trial protocol and the report of the trial respectively. A total of 154 patients with chronic low back pain were randomised to receive a motor control exercise program, or placebo (i.e. detuned short-wave therapy and detuned ultrasound therapy). Primary outcomes were pain, function, and the patient’s global impression of recovery measured at 2 months. The exercise intervention improved function and patient’s global impression of recovery, but not pain, at 2 months. The mean effect of exercise on function was 1.1 points (95%CI, 0.3 to 1.8), the mean effect on global impression of recovery was 1.5 points (95%CI, 0.4 to 2.5) and the mean effect on pain was 0.9 points (95%CI, - 0.01 to 1.8), all measured on 11 point scales. Secondary outcomes also favoured motor control exercise. This is the first study ever to demonstrate that motor control exercise is better than placebo for patients with chronic low back pain. Most of the treatment effects were maintained at 6 and 12 months follow-up. These results suggest that this intervention should be considered for patients with chronic low back pain in order to improve disability, function, and global impression of recovery, and to improve pain intensity in the long term, but not in the short term. Rehabilitative ultrasound imaging (RUSI) has been increasingly used by physiotherapists in order to identify impairments in motor control as well as to monitor progress of patients with low back pain. As with any other clinical measure it is important to know how reproducible the RUSI measures are, and although there are some reproducibility studies in the literature, no systematic review on this topic has been conducted. Therefore a systematic review was performed with the objective of assessing the reproducibility studies of RUSI for abdominal wall muscles (Chapter 4). Eligible studies were indentified via searches in CINAHL, EMBASE and MEDLINE with citation tracking via the Web of Science Index. A total of 21 studies were included. Due to heterogeneity of the studies’ designs, pooling the data for a meta-analysis was not possible. RUSI measures of thickness of abdominal wall muscles were found to be reliable. Few studies analysed the reliability for the measurement of thickness changes (reflecting the muscle activity) finding good to poor results. Evidence for the reproducibility of the difference in thickness changes over time (necessary to evaluate improvements in muscle activity with treatment) was not available. A limitation of the existing literature is that studies typically had suboptimal designs and analysis. The current evidence for the reproducibility of RUSI for measuring abdominal muscle activity is mainly based upon studies with suboptimal designs that included mostly healthy subjects, making generalisability to clinical settings uncertain. Some questions about the reproducibility of RUSI measures of abdominal wall muscles are still unanswered; this is mainly due to design issues, such as inadequate statistics, inadequate sampling and lack of control of sources of bias (e.g. blinding and absence of controlling for ordering effects). In addition the clinically important questions about the reproducibility of thickness changes (reflecting the muscle activity) and differences in thickness changes over time (reflecting the improvement or deterioration of muscle activity) have not been adequately investigated. Therefore a reproducibility study that aimed to answer these questions was performed (Chapter 5). Thirty-five patients seeking care for chronic low back pain participated in this study. RUSI measures were taken at baseline and eight weeks post-baseline. Replicate measures of thickness, thickness changes and differences in thickness changes over time were analysed. The reproducibility of static images (thickness) was excellent (ICC2,1 = 0.97, 95%CI = 0.96-0.97, Standard Error of the Measurement (SEM) = 0.04cm, Smallest Detectable Change (SDC) = 0.11cm), the reproducibility of thickness changes was moderate (ICC2,1 = 0.72, 95%CI 0.65-0.76 SEM = 15%, SDC 41%), while the reproducibility of differences in thickness changes over time was poor. Improvements in the test protocol should be undertaken in order to enhance the reproducibility of RUSI measures, especially for differences in thickness chang over time. Self-report outcome measures (questionnaires) are widely used by health care providers for measuring patient’s health status or treatment outcomes. Most of the questionnaires related to low back pain were developed in English and therefore their usefulness in non-English speaking countries is considerably limited. Cross-cultural adaptation and clinimetric testing are possibly the most efficient methods for solving this problem. Although there are many publications on the topic, a simple guide on how to perform a cross-cultural adaptation and clinimetric testing was not available. Therefore a “clinician-friendly” narrative review for Brazilian physical therapists (Chapter 6) was written. This review aimed firstly to explain the concepts and the relevance of cross-cultural adaptation and clinimetrics testing, secondly to summarise the current guidelines on the topic, thirdly to provide advice on how to choose a relevant questionnaire and finally how to evaluate the quality of an adapted questionnaire. Some examples of cross-cultural adaptations and clinimetrics testing of relevant low back pain questionnaires in the Brazilian-Portuguese language were also provided. Although the number of international versions of low back questionnaires is growing, to date it is unclear which questionnaires have been cross-culturally adapted and into which specific language. To answer these questions a systematic review was conducted in order to describe the available cross-cultural adaptations of low back pain self-report outcome measures and the clinimetric testing that has occurred for each adaptation (Chapter 7). Searches were performed in MEDLINE, EMBASE, CINALH and LILACS; these searches were supplemented with information from experts in the field of low back pain from 27 different countries to ensure that the results were comprehensive. Sixty-one adaptations were identified. While there are a large number of low back pain questionnaires available, very few have been adapted into other languages, particularly commonly spoken languages such as Mandarin, Hindi and Portuguese. The quality and comprehensiveness of clinimetric testing varied considerably, with the evaluation of reliability and construct validity most common. Further cross-cultural adaptation and clinimetric studies are clearly needed and special consideration must be given to study designs for clinimetric testing. The final aim of this thesis was to cross-culturally adapt self-report instruments relevant to the management of low back pain in Brazil. This was achieved by two independent studies. The first study (Chapter 8) aimed to cross-culturally adapt the Functional Rating Index (FRI) into Brazilian-Portuguese and to test the clinimetric properties of the FRI and also of an existing Brazilian-Portuguese version of the Roland Morris Disability Questionnaire (RMDQ) which was not fully evaluated in the original study. Both instruments were tested for internal consistency, reliability, construct validity, ceiling and floor effects and internal responsiveness in 140 chronic low back patients presenting for physiotherapy treatment in Brazil. Both instruments were considered reliable and valid for the measurement of disability in Brazilian-Portuguese speakers with low back pain, no ceiling or floor effects were detected, but the internal responsiveness of both instruments was considered small. The second study (Chapter 9) aimed to cross-culturally adapt the Patient-Specific Functional Scale (PSFS) and to perform a head-to-head comparison of the clinimetric properties of the PSFS, RMDQ and FRI. All instruments were tested for internal consistency, reliability, construct validity, ceiling and floor effects, internal and external responsiveness in 99 acute low back patients presenting for physiotherapy treatment in Brazil. In order to fully test the construct validity and external responsiveness, it was necessary to cross-culturally adapt the Pain Numerical Rating Scale and the Global Perceived Effect Scale. The results of this study demonstrate that the Brazilian-Portuguese versions of the RMDQ, FRI and PSFS have similar clinimetric properties to each other and to the original English versions; however the PSFS was the most responsive instrument. The results from the studies in Chapters 8 and 9 will benefit the understanding of low back pain by enabling international comparisons between studies conducted in Brazil and English speaking countries. In addition it will encourage researchers to include Brazilian- Portuguese speakers in their future clinical trials. Overall, the studies included in this thesis have provided an important contribution to the contemporary management of low back pain. Firstly the use of motor control exercise could be considered for patients with chronic low back pain as it produces improvements in global impression of recovery, function, disability and pain. Secondly RUSI measures of abdominal wall muscles in patients with low back pain were considered reproducible for the measurement of muscle activity, but not as an outcome measure to detect improvement/deterioration of muscle activity over the course of treatment. Thirdly just a few high-quality cross-cultural adaptations and clinimetrics testing for self-report outcome measures relevant to the management of low back pain are available, and clearly more studies in this area are needed. Finally the Brazilian-Portuguese versions of the Functional Rating Index, the Roland Morris Disability Questionnaire and the Patient-Specific Functional Scale have acceptable clinimetric properties and could be used in clinical practice as well as in research studies in Brazil.

PhD / Abstract Low back pain is a significant public health problem in many countries of the world being one of the major causes of work absence and disability. Although the outlook for evidence-based management of low back pain has greatly improved over the past decades, many questions remain. Questions related to treatment options, underlying mechanisms of treatment effects and optimal assessment of low back pain have yet to be fully addressed by researchers. The broad aim of this thesis therefore was to contribute to a better understanding of the contemporary management of low back pain by performing studies in these key research areas. Most clinical practice guidelines recommend exercise as an effective treatment option for chronic low back pain. However the evidence for this recommendation comes from trials that are not placebo-controlled and so this may potentially provide biased estimates of the effects of exercise. Therefore a randomised controlled trial testing the effect of motor control exercise versus placebo in patients with chronic low back pain was conducted. Chapters 2 and 3 describe the trial protocol and the report of the trial respectively. A total of 154 patients with chronic low back pain were randomised to receive a motor control exercise program, or placebo (i.e. detuned short-wave therapy and detuned ultrasound therapy). Primary outcomes were pain, function, and the patient’s global impression of recovery measured at 2 months. The exercise intervention improved function and patient’s global impression of recovery, but not pain, at 2 months. The mean effect of exercise on function was 1.1 points (95%CI, 0.3 to 1.8), the mean effect on global impression of recovery was 1.5 points (95%CI, 0.4 to 2.5) and the mean effect on pain was 0.9 points (95%CI, - 0.01 to 1.8), all measured on 11 point scales. Secondary outcomes also favoured motor control exercise. This is the first study ever to demonstrate that motor control exercise is better than placebo for patients with chronic low back pain. Most of the treatment effects were maintained at 6 and 12 months follow-up. These results suggest that this intervention should be considered for patients with chronic low back pain in order to improve disability, function, and global impression of recovery, and to improve pain intensity in the long term, but not in the short term. Rehabilitative ultrasound imaging (RUSI) has been increasingly used by physiotherapists in order to identify impairments in motor control as well as to monitor progress of patients with low back pain. As with any other clinical measure it is important to know how reproducible the RUSI measures are, and although there are some reproducibility studies in the literature, no systematic review on this topic has been conducted. Therefore a systematic review was performed with the objective of assessing the reproducibility studies of RUSI for abdominal wall muscles (Chapter 4). Eligible studies were indentified via searches in CINAHL, EMBASE and MEDLINE with citation tracking via the Web of Science Index. A total of 21 studies were included. Due to heterogeneity of the studies’ designs, pooling the data for a meta-analysis was not possible. RUSI measures of thickness of abdominal wall muscles were found to be reliable. Few studies analysed the reliability for the measurement of thickness changes (reflecting the muscle activity) finding good to poor results. Evidence for the reproducibility of the difference in thickness changes over time (necessary to evaluate improvements in muscle activity with treatment) was not available. A limitation of the existing literature is that studies typically had suboptimal designs and analysis. The current evidence for the reproducibility of RUSI for measuring abdominal muscle activity is mainly based upon studies with suboptimal designs that included mostly healthy subjects, making generalisability to clinical settings uncertain. Some questions about the reproducibility of RUSI measures of abdominal wall muscles are still unanswered; this is mainly due to design issues, such as inadequate statistics, inadequate sampling and lack of control of sources of bias (e.g. blinding and absence of controlling for ordering effects). In addition the clinically important questions about the reproducibility of thickness changes (reflecting the muscle activity) and differences in thickness changes over time (reflecting the improvement or deterioration of muscle activity) have not been adequately investigated. Therefore a reproducibility study that aimed to answer these questions was performed (Chapter 5). Thirty-five patients seeking care for chronic low back pain participated in this study. RUSI measures were taken at baseline and eight weeks post-baseline. Replicate measures of thickness, thickness changes and differences in thickness changes over time were analysed. The reproducibility of static images (thickness) was excellent (ICC2,1 = 0.97, 95%CI = 0.96-0.97, Standard Error of the Measurement (SEM) = 0.04cm, Smallest Detectable Change (SDC) = 0.11cm), the reproducibility of thickness changes was moderate (ICC2,1 = 0.72, 95%CI 0.65-0.76 SEM = 15%, SDC 41%), while the reproducibility of differences in thickness changes over time was poor. Improvements in the test protocol should be undertaken in order to enhance the reproducibility of RUSI measures, especially for differences in thickness chang over time. Self-report outcome measures (questionnaires) are widely used by health care providers for measuring patient’s health status or treatment outcomes. Most of the questionnaires related to low back pain were developed in English and therefore their usefulness in non-English speaking countries is considerably limited. Cross-cultural adaptation and clinimetric testing are possibly the most efficient methods for solving this problem. Although there are many publications on the topic, a simple guide on how to perform a cross-cultural adaptation and clinimetric testing was not available. Therefore a “clinician-friendly” narrative review for Brazilian physical therapists (Chapter 6) was written. This review aimed firstly to explain the concepts and the relevance of cross-cultural adaptation and clinimetrics testing, secondly to summarise the current guidelines on the topic, thirdly to provide advice on how to choose a relevant questionnaire and finally how to evaluate the quality of an adapted questionnaire. Some examples of cross-cultural adaptations and clinimetrics testing of relevant low back pain questionnaires in the Brazilian-Portuguese language were also provided. Although the number of international versions of low back questionnaires is growing, to date it is unclear which questionnaires have been cross-culturally adapted and into which specific language. To answer these questions a systematic review was conducted in order to describe the available cross-cultural adaptations of low back pain self-report outcome measures and the clinimetric testing that has occurred for each adaptation (Chapter 7). Searches were performed in MEDLINE, EMBASE, CINALH and LILACS; these searches were supplemented with information from experts in the field of low back pain from 27 different countries to ensure that the results were comprehensive. Sixty-one adaptations were identified. While there are a large number of low back pain questionnaires available, very few have been adapted into other languages, particularly commonly spoken languages such as Mandarin, Hindi and Portuguese. The quality and comprehensiveness of clinimetric testing varied considerably, with the evaluation of reliability and construct validity most common. Further cross-cultural adaptation and clinimetric studies are clearly needed and special consideration must be given to study designs for clinimetric testing. The final aim of this thesis was to cross-culturally adapt self-report instruments relevant to the management of low back pain in Brazil. This was achieved by two independent studies. The first study (Chapter 8) aimed to cross-culturally adapt the Functional Rating Index (FRI) into Brazilian-Portuguese and to test the clinimetric properties of the FRI and also of an existing Brazilian-Portuguese version of the Roland Morris Disability Questionnaire (RMDQ) which was not fully evaluated in the original study. Both instruments were tested for internal consistency, reliability, construct validity, ceiling and floor effects and internal responsiveness in 140 chronic low back patients presenting for physiotherapy treatment in Brazil. Both instruments were considered reliable and valid for the measurement of disability in Brazilian-Portuguese speakers with low back pain, no ceiling or floor effects were detected, but the internal responsiveness of both instruments was considered small. The second study (Chapter 9) aimed to cross-culturally adapt the Patient-Specific Functional Scale (PSFS) and to perform a head-to-head comparison of the clinimetric properties of the PSFS, RMDQ and FRI. All instruments were tested for internal consistency, reliability, construct validity, ceiling and floor effects, internal and external responsiveness in 99 acute low back patients presenting for physiotherapy treatment in Brazil. In order to fully test the construct validity and external responsiveness, it was necessary to cross-culturally adapt the Pain Numerical Rating Scale and the Global Perceived Effect Scale. The results of this study demonstrate that the Brazilian-Portuguese versions of the RMDQ, FRI and PSFS have similar clinimetric properties to each other and to the original English versions; however the PSFS was the most responsive instrument. The results from the studies in Chapters 8 and 9 will benefit the understanding of low back pain by enabling international comparisons between studies conducted in Brazil and English speaking countries. In addition it will encourage researchers to include Brazilian- Portuguese speakers in their future clinical trials. Overall, the studies included in this thesis have provided an important contribution to the contemporary management of low back pain. Firstly the use of motor control exercise could be considered for patients with chronic low back pain as it produces improvements in global impression of recovery, function, disability and pain. Secondly RUSI measures of abdominal wall muscles in patients with low back pain were considered reproducible for the measurement of muscle activity, but not as an outcome measure to detect improvement/deterioration of muscle activity over the course of treatment. Thirdly just a few high-quality cross-cultural adaptations and clinimetrics testing for self-report outcome measures relevant to the management of low back pain are available, and clearly more studies in this area are needed. Finally the Brazilian-Portuguese versions of the Functional Rating Index, the Roland Morris Disability Questionnaire and the Patient-Specific Functional Scale have acceptable clinimetric properties and could be used in clinical practice as well as in research studies in Brazil.

PhD / Abstract Low back pain is a significant public health problem in many countries of the world being one of the major causes of work absence and disability. Although the outlook for evidence-based management of low back pain has greatly improved over the past decades, many questions remain. Questions related to treatment options, underlying mechanisms of treatment effects and optimal assessment of low back pain have yet to be fully addressed by researchers. The broad aim of this thesis therefore was to contribute to a better understanding of the contemporary management of low back pain by performing studies in these key research areas. Most clinical practice guidelines recommend exercise as an effective treatment option for chronic low back pain. However the evidence for this recommendation comes from trials that are not placebo-controlled and so this may potentially provide biased estimates of the effects of exercise. Therefore a randomised controlled trial testing the effect of motor control exercise versus placebo in patients with chronic low back pain was conducted. Chapters 2 and 3 describe the trial protocol and the report of the trial respectively. A total of 154 patients with chronic low back pain were randomised to receive a motor control exercise program, or placebo (i.e. detuned short-wave therapy and detuned ultrasound therapy). Primary outcomes were pain, function, and the patient’s global impression of recovery measured at 2 months. The exercise intervention improved function and patient’s global impression of recovery, but not pain, at 2 months. The mean effect of exercise on function was 1.1 points (95%CI, 0.3 to 1.8), the mean effect on global impression of recovery was 1.5 points (95%CI, 0.4 to 2.5) and the mean effect on pain was 0.9 points (95%CI, - 0.01 to 1.8), all measured on 11 point scales. Secondary outcomes also favoured motor control exercise. This is the first study ever to demonstrate that motor control exercise is better than placebo for patients with chronic low back pain. Most of the treatment effects were maintained at 6 and 12 months follow-up. These results suggest that this intervention should be considered for patients with chronic low back pain in order to improve disability, function, and global impression of recovery, and to improve pain intensity in the long term, but not in the short term. Rehabilitative ultrasound imaging (RUSI) has been increasingly used by physiotherapists in order to identify impairments in motor control as well as to monitor progress of patients with low back pain. As with any other clinical measure it is important to know how reproducible the RUSI measures are, and although there are some reproducibility studies in the literature, no systematic review on this topic has been conducted. Therefore a systematic review was performed with the objective of assessing the reproducibility studies of RUSI for abdominal wall muscles (Chapter 4). Eligible studies were indentified via searches in CINAHL, EMBASE and MEDLINE with citation tracking via the Web of Science Index. A total of 21 studies were included. Due to heterogeneity of the studies’ designs, pooling the data for a meta-analysis was not possible. RUSI measures of thickness of abdominal wall muscles were found to be reliable. Few studies analysed the reliability for the measurement of thickness changes (reflecting the muscle activity) finding good to poor results. Evidence for the reproducibility of the difference in thickness changes over time (necessary to evaluate improvements in muscle activity with treatment) was not available. A limitation of the existing literature is that studies typically had suboptimal designs and analysis. The current evidence for the reproducibility of RUSI for measuring abdominal muscle activity is mainly based upon studies with suboptimal designs that included mostly healthy subjects, making generalisability to clinical settings uncertain. Some questions about the reproducibility of RUSI measures of abdominal wall muscles are still unanswered; this is mainly due to design issues, such as inadequate statistics, inadequate sampling and lack of control of sources of bias (e.g. blinding and absence of controlling for ordering effects). In addition the clinically important questions about the reproducibility of thickness changes (reflecting the muscle activity) and differences in thickness changes over time (reflecting the improvement or deterioration of muscle activity) have not been adequately investigated. Therefore a reproducibility study that aimed to answer these questions was performed (Chapter 5). Thirty-five patients seeking care for chronic low back pain participated in this study. RUSI measures were taken at baseline and eight weeks post-baseline. Replicate measures of thickness, thickness changes and differences in thickness changes over time were analysed. The reproducibility of static images (thickness) was excellent (ICC2,1 = 0.97, 95%CI = 0.96-0.97, Standard Error of the Measurement (SEM) = 0.04cm, Smallest Detectable Change (SDC) = 0.11cm), the reproducibility of thickness changes was moderate (ICC2,1 = 0.72, 95%CI 0.65-0.76 SEM = 15%, SDC 41%), while the reproducibility of differences in thickness changes over time was poor. Improvements in the test protocol should be undertaken in order to enhance the reproducibility of RUSI measures, especially for differences in thickness chang over time. Self-report outcome measures (questionnaires) are widely used by health care providers for measuring patient’s health status or treatment outcomes. Most of the questionnaires related to low back pain were developed in English and therefore their usefulness in non-English speaking countries is considerably limited. Cross-cultural adaptation and clinimetric testing are possibly the most efficient methods for solving this problem. Although there are many publications on the topic, a simple guide on how to perform a cross-cultural adaptation and clinimetric testing was not available. Therefore a “clinician-friendly” narrative review for Brazilian physical therapists (Chapter 6) was written. This review aimed firstly to explain the concepts and the relevance of cross-cultural adaptation and clinimetrics testing, secondly to summarise the current guidelines on the topic, thirdly to provide advice on how to choose a relevant questionnaire and finally how to evaluate the quality of an adapted questionnaire. Some examples of cross-cultural adaptations and clinimetrics testing of relevant low back pain questionnaires in the Brazilian-Portuguese language were also provided. Although the number of international versions of low back questionnaires is growing, to date it is unclear which questionnaires have been cross-culturally adapted and into which specific language. To answer these questions a systematic review was conducted in order to describe the available cross-cultural adaptations of low back pain self-report outcome measures and the clinimetric testing that has occurred for each adaptation (Chapter 7). Searches were performed in MEDLINE, EMBASE, CINALH and LILACS; these searches were supplemented with information from experts in the field of low back pain from 27 different countries to ensure that the results were comprehensive. Sixty-one adaptations were identified. While there are a large number of low back pain questionnaires available, very few have been adapted into other languages, particularly commonly spoken languages such as Mandarin, Hindi and Portuguese. The quality and comprehensiveness of clinimetric testing varied considerably, with the evaluation of reliability and construct validity most common. Further cross-cultural adaptation and clinimetric studies are clearly needed and special consideration must be given to study designs for clinimetric testing. The final aim of this thesis was to cross-culturally adapt self-report instruments relevant to the management of low back pain in Brazil. This was achieved by two independent studies. The first study (Chapter 8) aimed to cross-culturally adapt the Functional Rating Index (FRI) into Brazilian-Portuguese and to test the clinimetric properties of the FRI and also of an existing Brazilian-Portuguese version of the Roland Morris Disability Questionnaire (RMDQ) which was not fully evaluated in the original study. Both instruments were tested for internal consistency, reliability, construct validity, ceiling and floor effects and internal responsiveness in 140 chronic low back patients presenting for physiotherapy treatment in Brazil. Both instruments were considered reliable and valid for the measurement of disability in Brazilian-Portuguese speakers with low back pain, no ceiling or floor effects were detected, but the internal responsiveness of both instruments was considered small. The second study (Chapter 9) aimed to cross-culturally adapt the Patient-Specific Functional Scale (PSFS) and to perform a head-to-head comparison of the clinimetric properties of the PSFS, RMDQ and FRI. All instruments were tested for internal consistency, reliability, construct validity, ceiling and floor effects, internal and external responsiveness in 99 acute low back patients presenting for physiotherapy treatment in Brazil. In order to fully test the construct validity and external responsiveness, it was necessary to cross-culturally adapt the Pain Numerical Rating Scale and the Global Perceived Effect Scale. The results of this study demonstrate that the Brazilian-Portuguese versions of the RMDQ, FRI and PSFS have similar clinimetric properties to each other and to the original English versions; however the PSFS was the most responsive instrument. The results from the studies in Chapters 8 and 9 will benefit the understanding of low back pain by enabling international comparisons between studies conducted in Brazil and English speaking countries. In addition it will encourage researchers to include Brazilian- Portuguese speakers in their future clinical trials. Overall, the studies included in this thesis have provided an important contribution to the contemporary management of low back pain. Firstly the use of motor control exercise could be considered for patients with chronic low back pain as it produces improvements in global impression of recovery, function, disability and pain. Secondly RUSI measures of abdominal wall muscles in patients with low back pain were considered reproducible for the measurement of muscle activity, but not as an outcome measure to detect improvement/deterioration of muscle activity over the course of treatment. Thirdly just a few high-quality cross-cultural adaptations and clinimetrics testing for self-report outcome measures relevant to the management of low back pain are available, and clearly more studies in this area are needed. Finally the Brazilian-Portuguese versions of the Functional Rating Index, the Roland Morris Disability Questionnaire and the Patient-Specific Functional Scale have acceptable clinimetric properties and could be used in clinical practice as well as in research studies in Brazil.

Missing data is a potential source of bias in the results of randomised controlled trials (RCTs), which can have a negative impact on guidance derived from them, and ultimately patient care. This thesis aims to improve the understanding, handling, analysis and reporting of missing data in patient reported outcome measures (PROMs) for RCTs. A review of the literature provided evidence of discrepancies between recommended methodology and current practice in the handling and reporting of missing data. Particularly, missed opportunities to minimise missing data, the use of inappropriate analytical methods and lack of sensitivity analyses were noted. Missing data patterns were examined and found to vary between PROMs as well as across RCTs. Separate analyses illustrated difficulties in predicting missing data, resulting in uncertainty about assumed underlying missing data mechanisms. Simulation work was used to assess the comparative performance of statistical approaches for handling missing available in standard statistical software. Multiple imputation (MI) at either the item, subscale or composite score level was considered for missing PROMs data at a single follow-up time point. The choice of an MI approach depended on a multitude of factors, with MI at the item level being more beneficial than its alternatives for high proportions of item missingness. The approaches performed similarly for high proportions of unit-nonresponse; however, convergence issues were observed for MI at the item level. Maximum likelihood (ML), MI and inverse probability weighting (IPW) were evaluated for handling missing longitudinal PROMs data. MI was less biased than ML when additional post-randomisation data were available, while IPW introduced more bias compared to both ML and MI. A case study was used to explore approaches to sensitivity analyses to assess the impact of missing data. It was found that trial results could be susceptible to varying assumptions about missing data, and the importance of interpreting the results in this context was reiterated. This thesis provides researchers with guidance for the handling and reporting of missing PROMs data in order to decrease bias arising from missing data in RCTs.

Evidence-based policing (EBP) has emerged as a key strand of police innovation since Sherman’s (1998) Police Foundation lecture. However, for others EBP raises as many questions as answers. One of the most contentious areas is the role advocated for randomised controlled trials in testing practice and developing knowledge to support EBP. RCTs are controversial with some scholars who argue that policing is not comparable to medicine and that RCTs are unable to reflect the complexity of the police role and context. Even those who advocate the use of RCTs recognise that there are significant challenges in achieving the high dosage and high fidelity that a successful experiment requires. This dissertation responds to these challenges by analysing the completed randomised controlled trials in policing and using a case study, Operation Turning Point, to identify the factors that may contribute to the conduct and management of police field trials with high levels of treatment integrity. In the introduction, Chapter 1, the approach is set out, framed around grounded theory, to be developed in four, linked, chapters. Chapter 2 is focused on understanding treatment integrity in RCTs involving the police: A search for police RCTs is produced 122 Police RCTs completed and reported by 2016. The levels of treatment integrity are analysed. 78 of the 122 RCTs exceeded a 60% threshold, with 49 being above 90%. In Chapter 3, a “novice theory” is developed and tested as an explanation for levels of treatment integrity in police randomised controlled trials: Analysis of the 122 RCTs suggests that “novice theory” can provide an explanation for the general patterns of treatment integrity. Further detailed analysis suggested that there are, however, other factors which may be important in determining the treatment integrity. These are developed in Chapter 4, which centres on a case study of Operation Turning Point. Using published case studies and an analysis of juvenile justice RCTs, a potential framework of operational factors is developed that appear to be important in effective conduct and management. The Turning Point case study is used to develop and expand on those operational factors. Finally, taking the two together, the analysis concluded that, beyond the operational factors, there were some more strategic, “protective factors” that were also critical. These are developed in Chapter 5, by using the coding and analysis of interviews with a sample of key staff involved in Turning Point Our analysis suggests that novice theory needs to be understood in the context of both the operational and protective factors that we have identified. Taken together these findings indicate the potential advantages of building institutional frameworks in which the development of practitioners and researchers and the conduct and management of experimental research could be brought closer together. We conclude with ten recommendations designed to improve the treatment integrity of police RCTs.

Randomised, controlled trials are widely regarded as the gold standard by which the clinical effectiveness of healthcare products should be evaluated. Debate continues as to the value of this method of product assessment in a complex area such as wound care. Any method that is employed to define a product’s clinical value is, however, useless unless its ongoing effectiveness in a clinical area or with an individual patient is effectively monitored.

Clinical decision-making about psychological interventions is best supported by robust evidence and informed patient choice. Randomised controlled trials (RCTs) are the current gold standard in evaluating intervention effectiveness and identifying harm. At present, RCTs of psychological intervention are unlikely to include measurement of adverse effects and this is in part due to lack of consensus about this topic. A Delphi study was conducted with a panel of both professionals and people with personal experience of face-to-face psychotherapy across the spectrum of mental health difficulties to seek consensus on what to include on a measure of adverse effects. Fifty-four items derived from an initial list of 147 items generated by the panel, are included on the APTMOS outcome measure, which now in it's preliminary form now requires validation before use in RCTs. To date, the evidence for psychological interventions for psychosis and schizophrenia has not been synthesised, which is important to inform patient choice and decision-making. Network meta-analysis compares multiple interventions using direct evidence from randomised controlled trials (RCTs) and indirect evidence from the network. A systematic review of the literature identified 91 RCTs across 23 different intervention/control group categories. Psychological interventions were more effective at reducing total symptoms of psychosis than control groups. One intervention with a low risk of bias, mindfulness-based psychoeducation, was consistently identified as most effective, with large effect sizes. Subgroup analyses identified differential effectiveness in different settings and for different subgroups. Further high quality RCT evidence of the highest ranked interventions is required to inform updates to clinical guidelines of psychological interventions for psychosis.

Abstract Background The randomised-controlled trial (RCT) provides the best evidence for evaluating treatment effects and is accepted as a gold standard for clinical and regulatory decision making (1;2). One of the major challenges to the conduct of RCTs is the recruitment of adequate numbers of participants. Inadequate numbers reduce the power of a study to detect statistically significant treatment effects, and may cause delays, increased costs and failure to complete trials. The need for clinical trials in children has been increasingly recognised by the scientific community, resulting in increased demands for the inclusion of children in trials. For several reasons, recruiting children to trials is more challenging than recruiting adults, as consent issues are more difficult because parents make decisions about trial participation on behalf of their child. Despite general professional and community support for paediatric clinical trials, parents and paediatricians express reluctance when their own child or patient is asked to participate. Although researchers working with children commonly experience difficulty with recruiting children to RCTs, little is known about this very important subject. The method by which potential participants are approached for trial participation, the influence of their health care provider and the attitude of potential participants (or their parents, in the case of children), are critical to the understanding of the decision making process for trial participation. This thesis is one of the first major attempts to explore the issues surrounding the recruitment of children to RCTs, and is divided into four studies which address these issues. Methods Recruitment strategies used to encourage participation in randomised controlled trials (systematic review) Eligible experimental and observational studies comparing methods of recruiting participants for RCTs were identified after a comprehensive search of Medline, Embase, the Cochrane Library and reference lists. Independent data extractions were completed by two reviewers who assessed the studies for eligibility and methodological quality. Outcome measures were consent rates, proportion enrolled by each method and cost of recruitment per participant. Summary estimators of effects were calculated using a random effects model and expressed as relative risk with 95% confidence intervals. Heterogeneity was analysed using the Q statistic. Paediatricians� attitudes to children�s participation in randomised controlled trials (focus group research) Qualitative analysis of focus group discussions involving 16 paediatricians and 5 trainees from a paediatric teaching hospital in Sydney was undertaken. Doctors varied in occupation, experience, research activity, age, gender, ethnicity and parenthood experience. A professional facilitator conducted the semi-structured group discussions. Recruitment ceased when informational redundancy was reached, after 4 focus groups involving 21 participants. The transcribed audiotapes were analysed by theme linkage using the constant comparative method. Australian paediatricians� and adult physicians� attitudes to randomised controlled trials (survey) A 44-item questionnaire was sent to 250 paediatricians and 250 adult physicians randomly selected from the membership list of the Royal Australasian College of Physicians. Questions assessing doctors� treatment philosophies and attitudes to trials were compared with demographic and practice variables. Parents� attitudes to children�s participation in randomised controlled trials (focus group research) Qualitative analysis of focus group discussions involving 33 parents from 5 different settings (representing parents of children with a life threatening, chronic or acute illness, with experience in trials and of healthy children) was undertaken. Parents varied in age, gender, ethnicity, level of education, research experience and their child�s health status. The transcribed discussions were analysed by theme linkage using the constant comparative method. Results Recruitment strategies used to encourage participation in randomised controlled trials (systematic review) Fifty papers were included (out of 8602 titles and abstracts searched) which described 8 RCTs, 2 quasi RCTs, 13 prospective cohort studies, 30 retrospective cohort studies and 2 before-after studies. These studies assessed how over 4 million people were approached for RCT participation using 87 different recruitment strategies, with 103,406 people enrolling in RCTs. Health care provider (HCP) referrals had the highest participant consent rates at the time of exposure to trial information (HCP referral versus target mailing: relative risk (RR) 1.84 (95% confidence interval (95%CI) 1.08, 3.13)). They also had the highest consent rates when potential participants respond to the recruitment material by further enquiry about the trial (HCP referral versus community presentation: RR 1.37 (1.06; 1.78); HCP referral versus worksite approach: RR 25.20 (20.19, 31.45); HCP referral versus general community approach: RR 2.53 (0.46, 14.05); HCP referral versus mailing: RR 3.29 (1.26, 8.60); HCP referral versus media: RR 2.66 (1.31, 5.41)). However, by the time potential participants attend eligibility assessment for trial participation, no difference in consent rates could be distinguished by method of recruitment. Higher proportions of study participants were recruited by methods that exposed larger numbers of potential candidates to trial information (despite their lower consent rates). The stated recruitment cost ranged from US$0 to $1108 per participant, with mailing being the most cost-effective method and community methods (such as community presentations, pamphlets and posters displayed at community sites) the least effective. Paediatricians� attitudes to children�s participation in randomised controlled trials (focus group research) From the focus group discussions, paediatricians thought parents balanced perceived gains and risks when deciding about trial participation. They also believed the child�s condition and parents� health beliefs and personal attributes influenced parents� decisions. Other factors thought to be important by paediatricians were the doctors� beliefs and their relationship with the investigators. Paediatricians perceived gains for trial participation including professional benefits for themselves, improved patient care, convenience for the families and themselves and scientific advancement. Perceived risks included inconvenience, inadequate resources and potential harms to the patient and the doctor-patient relationship. Paediatricians with previous research experience were most knowledgeable about RCTs and perceived greatest gains from trial participation. Paediatricians� personal treatment preferences hindered trial support. Australian paediatricians� and adult physicians� attitudes to randomised controlled trials (survey) Response rate from the paediatricians� and adult physicians� survey was 60% (300/500). Australian paediatricians and adult physicians are very similar in their treatment philosophies, and are clinician-oriented rather than research-oriented in their attitudes, with primary allegiance to their patients and preference for selecting treatment rather than referring for trial participation in the face of treatment uncertainty. Professional activities are clinically focused, with limited time assigned for research. Australian doctors perceive little reward for trial participation and claim that the opinions of referring doctors regarding RCTs does not influence them. Predictors of favourable attitudes to trial participation from the survey were time allocation for research, a history of referring patients to trials in the past and younger age (all p values less than 0.0001). Parents� attitudes to children�s participation in randomised controlled trials (focus group research) When parents were interviewed, they acknowledged balancing risks and benefits when deciding about trial participation for their child. Perceived benefits include the offer of hope, better care of their child, the opportunity to access new treatments, healthcare professionals and health information, meeting others in similar circumstances and helping others. Perceived risks include potential side effects, being randomised to ineffective treatments and the inconvenience of participation. The decision for trial participation is also influenced by parental factors (parents� knowledge, beliefs and emotional response), child factors (the child�s health status and preference about participation), trial factors (the use of placebos and the uncertainties of research) and doctor factors (doctor�s recommendations and communication of trial information). Conclusions There are many challenges to the successful conduct of RCTs. Ways of addressing these include: using effective methods of recruiting potential study participants (such as mailing of recruitment material to potential participants) and abandoning ineffective strategies (such as community methods): fostering greater willingness for trial participation by addressing parents� and paediatricians� concerns including enhancing communication between researchers, paediatricians and parents, and improving the gains-hazard balance (by increasing incentives while decreasing inconveniences); and reforming in the health care system to raise the priority placed on clinical research by restructuring clinical research in a clinically predominant workplace and with a clinically predominant workforce. The findings from this study have implications for researchers planning RCTs for children in the future. Careful consideration of the above will enhance RCTs participation for children improving efficiency, lowering costs and ultimately improving the future health care of children.

Abstract Background The randomised-controlled trial (RCT) provides the best evidence for evaluating treatment effects and is accepted as a gold standard for clinical and regulatory decision making (1;2). One of the major challenges to the conduct of RCTs is the recruitment of adequate numbers of participants. Inadequate numbers reduce the power of a study to detect statistically significant treatment effects, and may cause delays, increased costs and failure to complete trials. The need for clinical trials in children has been increasingly recognised by the scientific community, resulting in increased demands for the inclusion of children in trials. For several reasons, recruiting children to trials is more challenging than recruiting adults, as consent issues are more difficult because parents make decisions about trial participation on behalf of their child. Despite general professional and community support for paediatric clinical trials, parents and paediatricians express reluctance when their own child or patient is asked to participate. Although researchers working with children commonly experience difficulty with recruiting children to RCTs, little is known about this very important subject. The method by which potential participants are approached for trial participation, the influence of their health care provider and the attitude of potential participants (or their parents, in the case of children), are critical to the understanding of the decision making process for trial participation. This thesis is one of the first major attempts to explore the issues surrounding the recruitment of children to RCTs, and is divided into four studies which address these issues. Methods Recruitment strategies used to encourage participation in randomised controlled trials (systematic review) Eligible experimental and observational studies comparing methods of recruiting participants for RCTs were identified after a comprehensive search of Medline, Embase, the Cochrane Library and reference lists. Independent data extractions were completed by two reviewers who assessed the studies for eligibility and methodological quality. Outcome measures were consent rates, proportion enrolled by each method and cost of recruitment per participant. Summary estimators of effects were calculated using a random effects model and expressed as relative risk with 95% confidence intervals. Heterogeneity was analysed using the Q statistic. Paediatricians� attitudes to children�s participation in randomised controlled trials (focus group research) Qualitative analysis of focus group discussions involving 16 paediatricians and 5 trainees from a paediatric teaching hospital in Sydney was undertaken. Doctors varied in occupation, experience, research activity, age, gender, ethnicity and parenthood experience. A professional facilitator conducted the semi-structured group discussions. Recruitment ceased when informational redundancy was reached, after 4 focus groups involving 21 participants. The transcribed audiotapes were analysed by theme linkage using the constant comparative method. Australian paediatricians� and adult physicians� attitudes to randomised controlled trials (survey) A 44-item questionnaire was sent to 250 paediatricians and 250 adult physicians randomly selected from the membership list of the Royal Australasian College of Physicians. Questions assessing doctors� treatment philosophies and attitudes to trials were compared with demographic and practice variables. Parents� attitudes to children�s participation in randomised controlled trials (focus group research) Qualitative analysis of focus group discussions involving 33 parents from 5 different settings (representing parents of children with a life threatening, chronic or acute illness, with experience in trials and of healthy children) was undertaken. Parents varied in age, gender, ethnicity, level of education, research experience and their child�s health status. The transcribed discussions were analysed by theme linkage using the constant comparative method. Results Recruitment strategies used to encourage participation in randomised controlled trials (systematic review) Fifty papers were included (out of 8602 titles and abstracts searched) which described 8 RCTs, 2 quasi RCTs, 13 prospective cohort studies, 30 retrospective cohort studies and 2 before-after studies. These studies assessed how over 4 million people were approached for RCT participation using 87 different recruitment strategies, with 103,406 people enrolling in RCTs. Health care provider (HCP) referrals had the highest participant consent rates at the time of exposure to trial information (HCP referral versus target mailing: relative risk (RR) 1.84 (95% confidence interval (95%CI) 1.08, 3.13)). They also had the highest consent rates when potential participants respond to the recruitment material by further enquiry about the trial (HCP referral versus community presentation: RR 1.37 (1.06; 1.78); HCP referral versus worksite approach: RR 25.20 (20.19, 31.45); HCP referral versus general community approach: RR 2.53 (0.46, 14.05); HCP referral versus mailing: RR 3.29 (1.26, 8.60); HCP referral versus media: RR 2.66 (1.31, 5.41)). However, by the time potential participants attend eligibility assessment for trial participation, no difference in consent rates could be distinguished by method of recruitment. Higher proportions of study participants were recruited by methods that exposed larger numbers of potential candidates to trial information (despite their lower consent rates). The stated recruitment cost ranged from US$0 to $1108 per participant, with mailing being the most cost-effective method and community methods (such as community presentations, pamphlets and posters displayed at community sites) the least effective. Paediatricians� attitudes to children�s participation in randomised controlled trials (focus group research) From the focus group discussions, paediatricians thought parents balanced perceived gains and risks when deciding about trial participation. They also believed the child�s condition and parents� health beliefs and personal attributes influenced parents� decisions. Other factors thought to be important by paediatricians were the doctors� beliefs and their relationship with the investigators. Paediatricians perceived gains for trial participation including professional benefits for themselves, improved patient care, convenience for the families and themselves and scientific advancement. Perceived risks included inconvenience, inadequate resources and potential harms to the patient and the doctor-patient relationship. Paediatricians with previous research experience were most knowledgeable about RCTs and perceived greatest gains from trial participation. Paediatricians� personal treatment preferences hindered trial support. Australian paediatricians� and adult physicians� attitudes to randomised controlled trials (survey) Response rate from the paediatricians� and adult physicians� survey was 60% (300/500). Australian paediatricians and adult physicians are very similar in their treatment philosophies, and are clinician-oriented rather than research-oriented in their attitudes, with primary allegiance to their patients and preference for selecting treatment rather than referring for trial participation in the face of treatment uncertainty. Professional activities are clinically focused, with limited time assigned for research. Australian doctors perceive little reward for trial participation and claim that the opinions of referring doctors regarding RCTs does not influence them. Predictors of favourable attitudes to trial participation from the survey were time allocation for research, a history of referring patients to trials in the past and younger age (all p values less than 0.0001). Parents� attitudes to children�s participation in randomised controlled trials (focus group research) When parents were interviewed, they acknowledged balancing risks and benefits when deciding about trial participation for their child. Perceived benefits include the offer of hope, better care of their child, the opportunity to access new treatments, healthcare professionals and health information, meeting others in similar circumstances and helping others. Perceived risks include potential side effects, being randomised to ineffective treatments and the inconvenience of participation. The decision for trial participation is also influenced by parental factors (parents� knowledge, beliefs and emotional response), child factors (the child�s health status and preference about participation), trial factors (the use of placebos and the uncertainties of research) and doctor factors (doctor�s recommendations and communication of trial information). Conclusions There are many challenges to the successful conduct of RCTs. Ways of addressing these include: using effective methods of recruiting potential study participants (such as mailing of recruitment material to potential participants) and abandoning ineffective strategies (such as community methods): fostering greater willingness for trial participation by addressing parents� and paediatricians� concerns including enhancing communication between researchers, paediatricians and parents, and improving the gains-hazard balance (by increasing incentives while decreasing inconveniences); and reforming in the health care system to raise the priority placed on clinical research by restructuring clinical research in a clinically predominant workplace and with a clinically predominant workforce. The findings from this study have implications for researchers planning RCTs for children in the future. Careful consideration of the above will enhance RCTs participation for children improving efficiency, lowering costs and ultimately improving the future health care of children.

Yes / An influential review in 2010 concluded that non-pharmacological multi-component interventions have positive effects on cognitive functioning, activities of daily living, behaviour and mood of people with dementia. Our aim here is to provide an up-to-date overview of research into psychosocial interventions and their impact on psychosocial outcomes. We focused on randomised controlled trials, controlled studies and reviews published between October 2008 and August 2015, since the earlier review. The search of PsychInfo, Medline and the Cochrane database of systematic reviews yielded 61 relevant articles, organised into four themes echoing key phases of the care pathway: Living at home with dementia (five reviews, eight studies), carer interventions (three reviews, four studies), interventions in residential care (16 reviews, 12 studies) and end-of-life care (three reviews, two studies), along with an additional group spanning community and institutional settings (six reviews, two studies). Community findings suggested that appointment of dementia specialists and attention to case management can produce positive outcomes; physical therapies, cognitive training and modified cognitive behaviour therapy also had a range of benefits. There was more limited evidence of positive benefits for people with dementia through interventions with family carers. Thirty-two articles focused on the management of ‘behavioural symptoms’ through a range of interventions all of which had some evidence of benefit. Also a range of multi-component and specific interventions had benefits for cognitive, emotional and behavioural well-being of people with dementia in residential settings, as well as for quality of life. Overall, interventions tended to be short term with impact only measured in the short term. We recommend further research on interventions to promote living well in the community post-diagnosis and to address end-of-life care. Development of psychosocial interventions would benefit from moving beyond the focus on control of behaviours to focus on wider aspects of life for people with dementia.