Incorporating quality of life measures in HIV clinical trials

Abstract

PURPOSE: To increase awareness regarding issues specific to health-related quality of life (HRQL) assessments for investigators designing clinical trials and for clinicians reading published reports on clinical trials. HQRL measures are becoming more prevalent, alongside conventional therapeutic and laboratory endpoints. However, they differ from these physiologic or biologic measurements because HRQL data are subjective. We discuss the criteria for selecting and implementing HRQL instruments to optimize the usefulness of HRQL assessments in clinical studies. METHOD: We conducted a review of selected design and measurement issues that should be considered when planning for the use of HRQL instruments in HIV/AIDS clinical trials. CONCLUSION: When used appropriately, HRQL measures can indicate the impact of HIV treatment on patient functioning and well-being and can help to inform clinicians about treatment effects.     

Brief report: assessing the impact of rating scale type, types of items, and age on the measurement of school-age children's self-reported quality of life

OBJECTIVE: To examine the effect of age, scale, and item type on the reliability and reproducibility of children's quality-of-life (QOL) responses. METHODS: The TedQL (ability, social, and mood items) was administered to 266 healthy children (age range of 5-6 and 7-9 years) at two time points, comparing three rating scales (circles, faces, and thermometer). Children were given the same (n = 144) or different (n = 122) scales over time. RESULTS: Reliability for total QOL and ability items was highest for circles and for social items using the faces. Faces and thermometer scales showed highest reproducibility over time. Greater agreement over time across different scales was found between circles and faces (5-6 years) and thermometer and circles (7-9 years). CONCLUSIONS: For maximum internal reliability, circles are recommended for ability items and faces for social items. For maximum reproducibility over time, the thermometer is recommended for 5-6 years and faces for 7-9 years.     

Efficacy and tolerability of renzapride in irritable bowel syndrome: a meta-analysis of randomized,controlled clinical trials including 2528 patients

Introduction

By targeting different subtypes of 5-hydroxytryptamine (5HT) receptors in the gastrointestinal (GI) tract, several drugs have been introduced for the management of irritable bowel syndrome (IBS). Renzapride is a full agonist for 5HT4 receptor and an antagonist to 5HT2b and 5HT3 receptors which is thought a promising therapeutic agent for constipation predominant IBS (C-IBS) patients due to its accelerating effect on the GI tract. In this meta-analysis, our aim was to evaluate the efficacy and tolerability of renzapride in the management of IBS.

Material and methods

A search was done from 1992 to February 2013 for placebo-controlled trials that investigated the efficacy of renzapride in IBS.

Results

Relative risk (RR) for clinical efficacy in IBS patients treated for 5 weeks or less comparing renzapride to placebo was 1.07 (95% CI = 0.89–1.29, p = 0.38). This value for IBS patients treated for more than 5 weeks was 1.04 (95% CI = 0.78–1.239, p = 0.77). The RR for clinical efficacy in IBS patients treated with renzapride (4 mg) for 5 weeks or less and more than 5 weeks in comparison to placebo was 1.2 (95% CI = 0.97–1.48, p = 0.1) and 1.16 (95% CI = 0.98–1.37, p = 0.08), respectively, which were statistically non-significant but clinically important. The analysis of tolerability demonstrated that amongst different reported adverse effects, renzapride caused diarrhea more than placebo (RR = 1.61 with a 95% CI = 1.16–2.24, p = 0.004). The RR for withdrawals from renzapride compared to placebo was 1.58 (95% CI = 1.26–2.07, p = 0.0007).

Conclusions

Renzapride is not superior to placebo in relieving IBS symptoms and causes significant incidences of diarrhea and drop-outs due to adverse effects in treated patients vs. placebo. Thus, this medicine might be a cost burden to patients without providing good effectiveness.     

Vasectomy techniques for male sterilization: systematic Cochrane review of randomized controlled trials and controlled clinical trials

BACKGROUND: The review aimed to compare the effectiveness, safety and acceptability of vasectomy techniques for male sterilization. METHODS: We searched five computerized databases and reference lists of relevant articles and book chapters for randomized controlled trials (RCTs) and controlled clinical trials (CCTs) comparing vasectomy techniques. Two reviewers independently extracted data from eligible articles. RESULTS: Two poor-quality trials compared vas occlusion with clips versus a conventional technique, and four poor-quality trials examined vas irrigation with water versus no irrigation or irrigation with euflavine. No significant differences regarding the primary outcome of time to azoospermia were found. However, one trial reported fewer median number of ejaculations to azoospermia with euflavine rather than water irrigation. An interim report of a high-quality trial comparing vasectomy with and without fascial interposition found more azoospermia with fascial interposition but also more surgical difficulties. CONCLUSIONS: No conclusions can be reached regarding the effectiveness, safety and acceptability of vas occlusion techniques or vas irrigation since only low-quality, underpowered studies were available. Fascial interposition had improved vasectomy success but also increased surgical difficulty. High-quality, adequately reported RCTs are required. More work is also needed in the standardization of follow-up protocols, evaluation of vasectomy success and failure, recanalization and analytical methods.     

Brief report: sleep in children with sickle cell disease: an analysis of daily diaries utilizing multilevel models

OBJECTIVE: To investigate the pain-sleep relationship in children with sickle cell disease (SCD) and the influence of stress and pain medication use on this relationship. METHOD: Children with SCD (n = 20; aged 8-12 years) completed daily diaries assessing sleep, pain, stress, and pain medication use for up to 2 months. Data analyzed using multilevel modeling. RESULTS: High daily pain was related to poor sleep quality that night and poor sleep quality was related to high pain the following day. High stress was related to less sleep. High same-day pain and pain medication attenuated the impact of pain on sleep quality. CONCLUSION: Results highlight the importance of sleep in addressing functioning in children with chronic pain, knowledge which may help patients and their families better manage the child's pain. Behavioral pain interventions may be improved by the inclusion of strategies to encourage proper sleep hygiene and address sleep issues.     

Development of tuberculosis vaccines in clinical trials: Current status

Tuberculosis (TB ) is an important infectious disease worldwide. Currently, Bacillus Calmette‐Guérin (BCG ) remains the only TB vaccine licensed for human use. This TB vaccine is effective in protecting children against severe military TB but offers variable protective efficacy in adults. Therefore, new vaccines against TB are needed to overcome this serious disease. At present, around 14 TB vaccine candidates are in different phases of clinical trials. These TB vaccines in clinical evaluation can be classified into two groups including preventive pre‐ and post‐exposure vaccines: subunit vaccines (attenuated viral vectors or adjuvanted fusion proteins), and whole‐cell vaccines (genetically attenuated Mycobacterium tuberculosis (M. tb ), recombinant BCG , killed M. tb or M. vaccae ). Although, over the last two decades a great progress in the search for a more effective TB vaccine has been demonstrated there is still no replacement for the licensed BCG vaccine. This article summarizes the current status of TB vaccine development and identifies crucial gaps of research for the development of an effective TB vaccine in all age groups.     

Clinical trials in the Journal of Pediatric Psychology: applying the CONSORT statement

OBJECTIVE: To determine how well therapeutic randomized controlled trials (RCTs) in the Journal of Pediatric Psychology (JPP) met the CONSORT criteria as compared to pediatric trials in the Journal of Clinical and Consulting Psychology (JCCP), which served as a control. METHODS: Nine trials were found in JPP and 19 clinical trials were retrieved from JCCP. The modified Consort Checklist and Flow Chart was applied to each trial by two unblinded independent raters. RESULTS: The number of CONSORT items not reported between the two journals was strikingly similar. One half (11/22) of the CONSORT items were reported less than 25% of the time. Information provided on the flow of participants in the trials was similar across the two journals; however, JCCP more often reported on those assessed to be eligible overall, chi(2) = 5.241, p <.05. JPP reported on recruitment 33.3% of the time, while it was not reported at all in JCCP, chi(2) = 7.093, p <.05. CONCLUSIONS: Although many of the items in the CONSORT statement were not adhered to by the two psychological journals, most of the CONSORT items can clearly be applied to psychosocial trials.     

Brief report: quality of life is impaired in pediatric burn survivors with posttraumatic stress disorder

Objective This study assessed health-related quality of life(HRQOL) and posttraumatic stress disorder (PTSD) in pediatricburn survivors and examined associations between PTSD and HRQOL.Methods Forty-three burn survivors, ages 7–16 years, wereinterviewed at an average of 4.4 years after their accidentusing the Clinician-Administered PTSD Scale for Children andAdolescents and the TNO-AZL Child Quality of Life Questionnaire.Results Eight children (18.6%) met DSM-IV criteria for currentPTSD. While most dimensions of HRQOL were within normal limits,social functioning was impaired. Severity of PTSD was significantlyassociated with physical, cognitive, and emotional dimensionsof HRQOL. Children with PTSD reported an impaired overall HRQOLand limited physical (e.g., more bodily complaints) and emotionalfunctioning (e.g., more feelings of sadness). Conclusions Thisstudy provides tentative evidence for a considerably high prevalenceof PTSD in pediatric burn survivors and for a negative associationbetween PTSD and HRQOL.     

Enhancing ventilation in homes of children with asthma: pragmatic randomised controlled trial

Background

Few robust studies have tested whether enhancing housing also improves health.

Aim

To evaluate the effectiveness of installing ventilation systems, and central heating where necessary, in the homes of children with moderate or severe asthma.

Design and setting

Pragmatic randomised controlled trial (RCT) in homes within Wrexham County Borough, Wales, UK.

Method

A pragmatic RCT was carried out, of a tailored package of housing improvements providing adequate ventilation and temperature, following inspection by a housing officer. One hundred and ninety-two children with asthma aged 5 to 14 years, identified from general practice registers, were randomised to receive this package, either immediately or a year after recruitment. At baseline, and after 4 and 12 months, parents reported their child''s asthma-specific and generic quality of life, and days off school.

Results

The package improved parent-reported asthma-specific quality of life significantly at both 4 and 12 months. At 12 months, this showed an adjusted mean difference between groups of 7.1 points (95% confidence interval [CI] = 2.8 to 11.4, P= 0.001): a moderate standardised effect size of 0.42. The generic quality-of-life scale showed reported physical problems were significantly reduced at 4 months, but not quite at 12 months, when the mean difference was 4.5 (95% CI = -0.2 to 9.1, P= 0.061). The improvement in psychosocial quality of life at 12 months was not significant, with a mean difference of 2.2 (95% CI = -1.9 to 6.4, P= 0.292). Parent-reported school attendance improved, but not significantly

Conclusion

This novel and pragmatic trial, with integrated economic evaluation, found that tailored improvement of the housing of children with moderate to severe asthma significantly increases parent-reported asthma-related quality of life and reduces physical problems. Collaborative housing initiatives have potential to improve health.     

Brief report: children's responses to trauma- and nontrauma-related hospital admission: a comparison study

OBJECTIVE: This study aims to investigate and compare psychological responses in children and parents 1 month after trauma- and nontrauma-related hospital admission. METHODS: Two hundred and five children aged 7-16 years (and their parents) were assessed for posttraumatic stress disorder (PTSD), other psychopathology, and distress 1 month after trauma-related (Trauma Group; n = 101) and nontrauma-related hospital admission (Non-Trauma Group; n = 104). RESULTS: Clinically elevated PTSD symptom levels were more prevalent in children admitted for trauma-related (18%) than nontrauma-related reasons (4%). Parents also experienced posttraumatic distress, although rates of clinically elevated symptom levels did not differ between the Trauma (11%) and Non-Trauma (8%) groups. Other pathology and distress in children and parents were comparable across groups. CONCLUSIONS: Children experienced greater posttraumatic distress following trauma-related hospital admission, while parents' experience of their child's hospitalization is equally distressing regardless of the reason for admission.     

Brief report: quality of life in overweight youth-the role of multiple informants and perceived social support

OBJECTIVE: To examine the impact of overweight status on pediatric quality of life (QOL). METHOD: This correlational study examined the relationship between weight, social support, race, informant, and QOL in a sample of 107 clinically overweight youth, ages 12 to 17 years. RESULTS: Regression analysis did not support the relation between QOL and weight. Social support was a significant predictor of youth reports of overall QOL. Males reported better physical QOL than females by both parent and youth report. Paired-samples t-tests supported a discrepancy between child and parent-proxy reports of QOL; parents reported significantly worse QOL than their children across many dimensions. Analysis of variance found no significant difference between Caucasian and African American youth's QOL. CONCLUSIONS: These results highlighted the importance of considering informant, gender, and the impact of social support when measuring QOL in clinically overweight pediatric populations.     

The important role of the histopathologist in clinical trials: challenges and approaches to tackle them

High-quality histopathology is essential for the success of clinical trials. Histopathologists have a detailed understanding of tumour biology and mechanisms of disease, as well as practical knowledge of optimal tissue handling and logistical service requirements for study delivery, such as biomarker evaluation, tissue acquisition and turnaround times. As such, histopathologist input is essential throughout every stage of research and clinical trials, from concept development and study design to trial delivery, analysis and dissemination of results. Patient recruitment to trials takes place among all healthcare settings, meaning that histopathologists make an invaluable contribution to clinical trials as part of their routine day-to-day work that often goes unrecognised. More complex evaluation of surgical specimens in the neoadjuvant setting and ever-expanding minimum data sets add to the workload of every histopathologist, not just academic pathologists in tertiary centres. This is occurring against a backdrop of increasing workload pressures and a worldwide shortage of histopathologists and biomedical scientists. Providing essential histopathology support for trials at grassroots level requires funding for adequate resources including histopathologist time, education and training, biomedical scientist and administrative support and greater recognition of the contribution made by histopathology. This paper will discuss the many ways in which histopathologists are involved in clinical trials and the challenges faced in meeting the additional demands posed by trial participation and potential ways to address this, with a special emphasis on the UK model and the Cellular–Molecular Pathology Initiative (CM-Path).     

Maximising recruitment and retention of general practices in clinical trials: a case study

Background

There is limited evidence regarding the factors that facilitate recruitment and retention of general practices in clinical trials. It is therefore pertinent to consider the factors that facilitate research in primary care.

Aim

To formulate hypotheses about effective ways of recruiting and retaining practices to clinical trials, based on a case study.

Design of study

Case study of practice recruitment and retention to a trial of delivering antenatal sickle cell and thalassaemia screening.

Setting

Two UK primary care trusts with 123 practices, with a high incidence of sickle cell and thalassaemia, and high levels of social deprivation.

Method

Practices were invited to take part in the trial using a research information sheet for practices. Invitations were sent to all practice managers, GPs, practice nurses, and nurse practitioners. Expenses of approximately £3000 per practice were available. Practices and the research team signed research activity agreements, detailing a payment schedule based on deliverables. Semi-structured interviews were completed with 20 GPs who participated in the trial. Outcome measures were the number of practices recruited to, and completing, the trial.

Results

Four practices did not agree to randomisation and were excluded. Of 119 eligible practices, 29 expressed an interest in participation. Two practices withdrew from the trial and 27 participated (two hosted pilot studies and 25 completed the trial), giving a retention rate of 93% (27/29). The 27 participating practices did not differ from non-participating practices in list size, number of GPs, social deprivation, or minority ethnic group composition of the practice population.

Conclusion

Three factors appeared important in recruiting practices: research topic, invitation method, and interest in research. Three factors appeared important in retaining practices: good communication, easy data-collection methods, and payment upon meeting pre-agreed targets. The effectiveness of these factors at facilitating recruitment and retention requires assessment in experimental studies.     

Re-adapting T cells for cancer therapy: from mouse models to clinical trials

Adoptive T-cell therapy involves the isolation, expansion, and reinfusion of T lymphocytes with a defined specificity and function as a means to eradicate cancer. Our research has focused on specifying the requirements for tumor eradication with antigen-specific T cells and T cells transduced to express a defined T-cell receptor (TCR) in mouse models and then translating these strategies to clinical trials. Our design of T-cell-based therapy for cancer has reflected efforts to identify the obstacles that limit sustained effector T-cell activity in mice and humans, design approaches to enhance T-cell persistence, develop methods to increase TCR affinity/T-cell functional avidity, and pursue strategies to overcome tolerance and immunosuppression. With the advent of genetic engineering, a highly functional population of T cells can now be rapidly generated and tailored for the targeted malignancy. Preclinical studies in faithful and informative mouse models, in concert with knowledge gained from analyses of successes and limitations in clinical trials, are shaping how we continue to develop, refine, and broaden the applicability of this approach for cancer therapy.     

Brief report: the impact of maternal posttraumatic stress disorder symptoms and child gender on risk for persistent posttraumatic stress disorder symptoms in child trauma victims

OBJECTIVE: To longitudinally examine the impact of maternal posttraumatic stress disorder symptoms (PTSS) on child adjustment following a child's traumatic injury, focusing on child gender differences. METHODS: Forty-one child traumatic injury victims aged 8-18 years and their biological mothers were interviewed over two follow-ups (6 weeks and 7 months). Children were administered the Clinician-Administered Posttraumatic Stress Disorder (PTSD) Scale for Children and Adolescents (CAPS-CA), whereas mothers completed the CAPS. RESULTS: Six weeks post trauma, maternal PTSS were significantly related to PTSS in boys but not in girls. However, at 7 months, maternal PTSS were strongly related to child PTSS in both boys and girls. Significant 6-week maternal distress-child gender interactions suggested that maternal PTSS, especially avoidance, predicted greater 7-month PTSS but that this was primarily because of a significant relationship in females. CONCLUSIONS: Maternal distress was found to negatively impact subsequent child adjustment, particularly in females. These results underscore the importance of considering family-centered interventions for child PTSD, especially in girls.     

Sublingual immunotherapy: efficacy – methodology and outcome of clinical trials

Using Medline we identified 39 placebo-controlled, double-blind sublingual immunotherapy (SLIT) studies providing symptom–medication score. These were retrospectively evaluated for evidence of clinical efficacy and quality of study presentation. Clinical efficacy was estimated according to statistical significance and graded as: unequivocal efficacy (statistically significant difference from placebo in both symptom and medication scores or the combined score), which was observed in 28% of studies, possible efficacy (significant improvement in either symptom or medication scores) seen in 33%, and no efficacy (no statistical difference between active treatment and the placebo group), as found in 38% of studies. Generally, studies were limited by the number of patients, showed a high frequency of withdrawals, a short duration of treatment, and insufficient data on randomization. The magnitude of efficacy additional to placebo treatment must be >20% in order to justify the treatment. This review concludes that future SLIT studies should be planned in accordance with international recommendations in order to be conclusive.     

Brief report: Optimizing children's memory and management of an invasive medical procedure: the influence of procedural narration and distraction

OBJECTIVE: To evaluate the influence of two interventions on children's memory of and distress during a voiding cysto-urethrogram (VCUG, X-ray of the kidneys). METHODS: Sixty-two children (aged 2.5-7.5 years) were allocated to one of three conditions. In one (CI + D), they received complete procedural information during the VCUG, with a cartoon video. In a second (PI + D), children received limited procedural information, with a cartoon video. In a third (standard care, PI), they received limited procedural information. VCUGs were videotaped and distress was coded using the CAMPIS-R. To assess memory, children were interviewed 1 week later. RESULTS: Relative to the PI condition, children in the CI + D condition recalled more information, appraised the VCUG as less painful, and were less distressed. There were no differences between the PI + D and PI conditions. CONCLUSIONS: An inexpensive, theoretically driven intervention can enhance children's memory and reduce distress during an invasive procedure.     

Update of sarilumb to treat rheumatoid arthritis based on randomized clinical trials: a systematic review

Introduction: Sarilumab is a human monoclonal antibody against Interleukin 6 α (IL-6α) receptor. Compared to tocilizumab, another IL-6 α receptor antibody, sarilumab has a different structure and higher affinity.

Areas covered: In a systematic literature review, we examined all sarilumab randomized clinical trials (RCTs) in rheumatoid arthritis. The 6 reviewed RCTs included patients who were inadequate MTX, DMARD and/or TNFi responders. Sarilumab 150–200 mg every 2 weeks improved RA signs, symptoms, function and decreased radiological progression up to 52 weeks. The most common adverse events were infections and neutropenia, the latter of which will require careful observation in future trials.

Examination of the effect of sero-positivity, disease duration, presence of erosions, use of previous biologic and comparisons to other biologics etc are still needed to complete understanding of this drug’s profile. Long term studies, too, will be needed to assess long term tolerability

Expert commentary: Results support the use of sarilumab to treat RA patients with inadequate response to MTX, other DMARDs and TNFis, although further studies are needed to fully assess its toxicity and understand the specific place of sarilumab in the RA armamentarium.