Health-related quality of life in patients accessing medicinal cannabis in Australia: The QUEST initiative results of a 3-month follow-up observational study.

AIMS: Patients with chronic health conditions not responding to conventional treatment can access medicinal cannabis (MC) prescriptions from clinicians in Australia. We aimed to assess overall health-related quality of life (HRQL), pain, fatigue, sleep, anxiety, and depression in a large real-world sample of patients accessing prescribed medicinal cannabis. We hypothesized that all patient-reported outcomes (PROs) would improve from baseline to 3-months. METHODS: The QUEST Initiative is a large prospective multicenter study of patients with any chronic health condition newly prescribed medicinal cannabis between November 2020 and December 2021. Eligible patients were identified by 120 clinicians at medical centers across six Australian states. Consenting participants completed the EuroQol Group EQ-5D-5L health status questionnaire; European Organization for Research & Treatment of Cancer Quality of Life questionnaire (QLQ-C30); Patient-Reported Outcomes Measurement Information System (PROMIS) Short Forms in Fatigue and Sleep Disturbance, and the Depression Anxiety Stress Scale (DASS-21) before starting therapy, at 2-weeks titration, then monthly for 3-months. RESULTS: Of the 2762 consenting participants, 2327 completed baseline and at least one follow-up questionnaire. Ages ranged between 18-97 years (mean 51y; SD = 15.4), 62.8% were female. The most commonly treated conditions were chronic pain (n = 1598/2327; 68.7%), insomnia (n = 534/2327; 22.9%), generalized anxiety (n = 508/2327; 21.5%), and mixed anxiety and depression (n = 259/2327; 11%). Across the whole cohort both EQ-5D-5L utility scores and QLQ-C30 summary scores showed clinically meaningful improvement in HRQL from baseline to mean follow-up with d = 0.54 (95%CI:0.47 to 0.59) and d = 0.64 (95%CI:0.58 to 0.70) respectively; and clinically meaningful improvement in fatigue (d = 0.54; 95%CI:0.48 to 0.59). There was clinically meaningful reduction of pain for those with chronic pain (d = 0.65; 95%CI:0.57 to 0.72); significant improvements for those with moderate to extremely severe anxiety (X2 = 383; df = 4; p<0.001) and depression (X2 = 395; df = 4; p<0.001); and no changes in sleep disturbance. CONCLUSIONS: We observed statistically significant, clinically meaningful improvements in overall HRQL and fatigue over the first 3-months in patients with chronic health conditions accessing prescribed medical cannabis. Anxiety, depression, and pain also improved over time, particularly for those with corresponding health conditions. The study continues to follow-up patients until 12-months to determine whether improvements in PROs are maintained long-term. TRAIL REGISTRATION: Study registration - Australian New Zealand Clinical Trials Registry: ACTRN12621000063819. https://www.australianclinicaltrials.gov.au/anzctr/trial/ACTRN12621000063819.

The Psychology of COVID-19 Booster Hesitancy, Acceptance and Resistance in Australia.

COVID-19 booster vaccinations have been recommended as a primary line of defence against serious illness and hospitalisation. This study identifies and characterises distinct profiles of attitudes towards vaccination, particularly the willingness to get a booster dose. A sample of 582 adults from Australia completed an online survey capturing COVID-related behaviours, beliefs and attitudes and a range of sociodemographic, psychological, political, social and cultural variables. Latent Profile Analysis (LPA) identified three subgroups: Acceptant (61%), Hesitant (30%) and Resistant (9%). Compared to the Acceptant group, the Hesitant and Resistant groups were less worried about catching COVID-19, used fewer official COVID-19 information sources, checked the news less, were lower on the agreeableness personality dimension and reported more conservatism, persecutory thinking, amoral attitudes and need for chaos. The Hesitant group also reported checking the legitimacy of information sources less, scored lower on the openness to new experiences personality dimension and were more likely than the Resistant and Acceptant groups to report regaining freedoms (e.g., travel) and work requirements or external pressures as reasons to get a booster. The Resistant group were higher on reactance, held more conspiratorial beliefs and rated their culture as being less tolerant of deviance than the Hesitant and Acceptant groups. This research can inform tailored approaches to increasing booster uptake and optimal strategies for public health messaging.

Health-related quality of life of Australians during the 2020 COVID-19 pandemic: a comparison with pre-pandemic data and factors associated with poor outcomes.

PURPOSE: Compare the health-related quality of life (HRQL) of the Australian general population during the COVID-19 pandemic (2020) with pre-pandemic data (2015-2016) and identify pandemic-related and demographic factors associated with poorer HRQL. METHODS: Participants were quota sampled from an online panel by four regions (defined by active COVID-19 case numbers); then by age and sex. Participants completed an online survey about their HRQL [EORTC QLQ-C30 questionnaire and General Health Question (GHQ)], demographic characteristics, and the impact of the pandemic on daily life. HRQL scores were compared to a 2015-2016 reference sample using independent t-tests, adjusted for multiple testing. Associations between 22 pre-specified factors (pandemic-related and demographic) and 15 QLQ-C30 domains and GHQ, were assessed with multiple regressions. RESULTS: Most domains were statistically significantly worse for the 2020 sample (n = 1898) compared to the reference sample (n = 1979), except fatigue and pain. Differences were largest for the youngest group (18-29 years) for cognitive functioning, nausea, diarrhoea, and financial difficulties. Emotional functioning was worse for 2020 participants aged 18-59, but not for those 60 +. All models were statistically significant at p < .001; the most variance was explained for emotional functioning, QLQ-C30 global health/QOL, nausea/vomiting, GHQ, and financial difficulties. Generally, increased workload, negative COVID-19 impacts, COVID-19-related worries, and negative attitudes towards public health order compliance were associated with poorer HRQL outcomes. CONCLUSION: During the COVID-19 pandemic, Australians reported poorer HRQL relative to a pre-pandemic sample. Risk factors for poor HRQL outcomes included greater negative pandemic-related impacts, poorer compliance attitudes, and younger age. TRIAL REGISTRATION: ANZCTR number is: ACTRN12621001240831. Web address of your trial: https://www.anzctr.org.au/ACTRN12621001240831.aspx . Date submitted: 26/08/2021 2:56:53 PM. Date registered: 14/09/2021 9:40:31 AM. Registered by: Margaret-Ann Tait. Principal Investigator: Madeleine King.

Improving the patient-reported outcome sections of clinical trial protocols: a mixed methods evaluation of educational workshops.

INTRODUCTION: Failure to incorporate key patient-reported outcome (PRO) content in trial protocols affects the quality and interpretability of the collected data, contributing to research waste. Our group developed evidence-based training specifically addressing PRO components of protocols. We aimed to assess whether 2-day educational workshops improved the PRO completeness of protocols against consensus-based minimum standards provided in the SPIRIT-PRO Extension in 2018. METHOD: Annual workshops were conducted 2011-2017. Participants were investigators/trialists from cancer clinical trials groups. Although developed before 2018, workshops covered 15/16 SPIRIT-PRO items. Participant feedback immediately post-workshop and, retrospectively, in November 2017 was summarised descriptively. Protocols were evaluated against SPIRIT-PRO by two independent raters for workshop protocols (developed post-workshop by participants) and control protocols (contemporaneous non-workshop protocols). SPIRIT-PRO items were assessed for completeness (0 = not addressed, 10 = fully addressed). Mann-Whitney U tests assessed whether workshop protocols scored higher than controls by item and overall. RESULTS: Participants (n = 107) evaluated the workshop positively. In 2017, 16/41 survey responders (39%) reported never applying in practice; barriers included role restrictions (14/41, 34%) and lack of time (5/41, 12%). SPIRIT-PRO overall scores did not differ between workshop (n = 13, median = 3.81/10, interquartile range = 3.24) and control protocols (n = 9, 3.51/10 (2.14)), (p = 0.35). Workshop protocols scored higher than controls on two items: 'specify PRO concepts/domains' (p = 0.05); 'methods for handling missing data' (p = 0.044). CONCLUSION: Although participants were highly satisfied with these workshops, the completeness of PRO protocol content generally did not improve. Additional knowledge translation efforts are needed to assist protocol writers address SPIRIT-PRO guidance and avoid research waste that may eventuate from sub-optimal PRO protocol content.

A Quality-of-Life Evaluation Study Assessing Health-Related Quality of Life in Patients Receiving Medicinal Cannabis (the QUEST Initiative): Protocol for a Longitudinal Observational Study.

BACKGROUND: Evidence supports several countries introducing legislation to allow cannabis-based medicine as an adjunctive treatment for the symptomatic relief of chronic pain, chemotherapy-induced nausea, spasticity in multiple sclerosis (MS), epileptic seizures, depression, and anxiety. However, clinical trial participants do not represent the entire spectrum of disease and health status seen in patients currently accessing medicinal cannabis in practice. OBJECTIVE: This study aims to collect real-world data to evaluate health-related quality of life in patients prescribed medicinal cannabis oil and describe any differences over time, from before starting therapy to after 3 and 12 months of therapy. METHODS: Adult patients newly prescribed medicinal cannabis oil by authorized prescribers and under the Special Access Schemes across Australia will be screened for eligibility and invited to participate. A sample size of 2142 is required, with a 3-month follow-up. All participants will complete the EuroQol 5-Dimension; European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-30; Depression, Anxiety, and Stress Scale-21; Patients' Global Impression of Change; Patient-Reported Outcomes Measurement Information System (PROMIS) Short Form (SF) version 1.0: Sleep Disturbance 8b; and PROMIS SF Fatigue 13a questionnaires. Patients with chronic pain conditions will also complete the PROMIS SF version 1.0: Pain Intensity 3a and PROMIS SF version 1.0: Pain Interference 8a. Patients with movement disorders will also complete Quality of Life in Neurological Disorders (Neuro-QoL) SF version 1.0: Upper Extremity Function (Fine Motor and Activities of Daily Living) and if chorea is indicated, the Neuro-QoL SF version 2.0: Huntington's Disease health-related Quality of LIFE-Chorea 6a. All questionnaires will be administered at baseline, 2 weeks (titration), monthly up to 3 months, and then every 2 months up to 1 year. RESULTS: Recruitment commenced in November 2020. By June 2021, 1095 patients were screened for the study by 69 physicians in centers across 6 Australian states: Australian Capital Territory, New South Wales, Queensland, South Australia, Victoria, and Western Australia. Of the patients screened, 833 (39% of the target sample size) provided consent and completed baseline questionnaires. Results are expected to be published in 2022. Results of this study will show whether patient-reported outcomes improve in patients accessing prescribed medicinal cannabis from baseline to 3 months and whether any changes are maintained over a 12-month period. This study will also identify differences in improvements in patient-reported outcomes among patients with different chronic conditions (eg, chronic pain, MS, epilepsy, Parkinson disease, or cancer). CONCLUSIONS: This protocol contains detailed methods that will be used across multiple sites in Australia. The findings from this study have the potential to be integral to treatment assessment and recommendations for patients with chronic pain and other health indicators for accessing medicinal cannabis. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry: ANZCTRN12621000063819; https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=380807&isReview=true. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/32327.

How is quality of life defined and assessed in published research?

PURPOSE: To ensure clarity in communication in the field of quality of life research, and meaningful use of 'quality of life' as a research outcome, requires two things: awareness that there is a range of conceptualisations and definitions of 'quality of life', and for any particular study, consistency between the way the term is defined and operationalised in that setting. We aimed to identify how frequently research articles described (HR)QOL as a construct of interest, how frequently they referred to "patient-reported outcome (measures)", which patient-reported outcome measures were used, and how (HR)QOL was defined. METHODS: We reviewed all Quality of Life Research articles published in 2017 and recorded whether they described health-related quality of life or quality of life as constructs of interest, and/or mentioned the term(s) patient-reported outcome (measures). We recorded definitions of (HR)QOL stated and questionnaires used. We classified articles according to constructs assessed and instruments used, and examined whether articles citing the same definition used the same questionnaires. RESULTS: We reviewed 300 articles; 65% stated that (HR)QOL was a construct of interest, 27% mentioned patient-reported outcome (measures), and 20% mentioned neither. Fifty-one articles provided definitions of (HR)QOL, citing 66 sources, with 11 definitions cited more than once. PROMIS, SF, EQ-5D, and EORTC instruments were the most commonly used. The only definition and questionnaire consistently used together were the WHO definitions/instruments. CONCLUSION: These results demonstrate considerable heterogeneity in the definition and operationalisation of (HR)QOL, between and within studies. This limits meaningful interpretation of (HR)QOL scores and complicates literature searches. Investigators should define constructs and select instruments aligned with their definitions.

Patient-reported outcomes in non-muscle invasive bladder cancer: a mixed-methods systematic review.

OBJECTIVE: Non-muscle invasive bladder cancer (NMIBC) is a chronic condition requiring repeated treatment and endoscopic examinations that can occur life-long. In this context, patient-reported outcomes (PROs) are important considerations to patients and managing clinicians. We undertook a systematic review to synthesise PRO results relevant to NMIBC treatment to explore trajectories overtime and differences between treatment options. METHODS: We searched databases AMED, MEDLINE, EMbase, PsycINFO, Web of Knowledge and Scopus (inception to 5th December 2019), reference lists and contacted key authors to identify studies that reported PROs after NMIBC treatment. Two reviewers independently applied inclusion and quality criteria and extracted findings. Results for PROs were synthesised for treatment groups across three time periods: acute/during induction therapy; during maintenance therapy; and long-term follow-up (> 1 year). RESULTS: Of 3193 papers screened, 29 were eligible. These provided evidence about induction treatment effects, but few reported maintenance or long-term evidence, and evidence about differences between NMIBC treatment options was lacking. A range of symptoms (pain in bladder area, urinary frequency and urgency, pain or burning during urination) were commonly experienced during and soon after treatment for NMIBC. Less common symptoms included fatigue, disrupted sleep and gastrointestinal problems. CONCLUSIONS: Treatments for NMIBC can cause symptoms and functional impairment during the acute treatment phase and reduce quality of life. Clinicians should be aware of these impairments to prepare patients for short-term sequelae and enable those with treatment options to exercise preferences in choosing among them. However, gaps in current evidence limit our understanding of PRO trajectories from diagnosis through to long-term survivorship and treatment effects.

Trials with proxy-reported outcomes registered on the Australian New Zealand Clinical Trials Registry (ANZCTR).

AIMS: A proxy is someone other than a patient who reports a patient's outcomes as if they are the patient. Due to known discordance with patient reports, proxies are often not recommended in clinical trials; however, proxies may be needed in certain research contexts. We aimed to identify and describe trials registered on the Australian New Zealand Clinical Trials Registry (ANZCTR) with proxy-reported endpoints. METHODS: ANZCTR was systematically searched from inception (2005) to 31 March 2017 for trials with proxy-reported endpoints. Primary and secondary endpoints for each trial retrieved by the search were individually coded (proxy-reported: yes/no), and trials with confirmed proxy-reported endpoints were included in the analysis. RESULTS: Of 13,666 registered trials, 469 (3.4%) included a proxy-reported endpoint (867 individual proxy-reported endpoints in total: 62% family member proxy, 22% health professional). Proxy endpoint inclusion did not significantly increase over time (r = 0.18, p = 0.59). Mental health (11.5%), stroke (10.3%) and neurological (8.3%) trials had the highest proportion of trials using proxies. Of the 469 trials, 123 (26.2%) studies involved paediatric patients. DISCUSSION: Proxy-reported endpoints are included in a small but notable number of studies, which may indicate other types of outcomes are used for patients unable to self-report, or that these patients are under-researched.

Correction to: Trials with patient-reported outcomes registered on the Australian New Zealand Clinical Trials Registry (ANZCTR).

In the original publication of the article, the sentence "The ANZCTR is the fifth largest trial registry internationally, with 21,330 registered trials as at January 2018 [5]" in the Introduction section was published incorrectly.

Trials with patient-reported outcomes registered on the Australian New Zealand Clinical Trials Registry (ANZCTR).

AIMS: It is important to understand the number, types and regions of trials that include patient-reported outcomes (PROs) to appreciate how patient experiences have been considered in studies of health and interventions. Twenty-seven percent of trials registered with ClinicalTrials.gov (2007-2013) included PROs; however, a regional breakdown was not provided and no reviews have been conducted of the Australia New Zealand Clinical Trials Registry (ANZCTR). We aimed to identify trials registered with ANZCTR with PRO endpoints and describe their characteristics. METHODS: ANZCTR was systematically searched from inception (2005) to 31 March 2017 for trials with PRO endpoints. Search terms included PRO measures listed in Patient-Reported Outcomes Quality of Life Instrument Database and Grid-Enabled Measures, as well as generic PRO terms (e.g. "quality of life" (QOL)). Trial endpoints were individually coded using an established framework to identify trials with PROs for the analysis. RESULTS: Of 13,666 registered trials, 6168 (45.1%) included a PRO. The proportion of studies including PROs increased between 2006 and 2016 (r = 0.74, p = 0.009). Among the 6168 trials, there were 17,961 individual PRO endpoints, including symptoms/functional outcomes/condition-specific QOL (65.6%), generic QOL (13.2%), patient-reported experiences (9.9%), patient-reported behaviours (7.9%). Mental health was the most common category (99.8% included PROs), followed by physical medicine/rehabilitation (65.6%), musculoskeletal (63.5%), public health (63.1%), and cancer (54.2%). DISCUSSION: Our findings suggest growing use of PROs in the assessment of health and interventions in ANZ. Our review identifies trial categories with limited patient-reported information and provides a basis for future work on the impact of PRO findings in clinical care.

Assessment of content validity for patient-reported outcome measures used in patients with non-muscle invasive bladder cancer: a systematic review.

OBJECTIVE: Non-muscle invasive bladder cancer (NMIBC) is a chronic condition requiring ongoing treatment and endoscopic examinations that are frequent and can be life-long. To ensure the comprehensive assessment of the benefits and harms of treatments for NMIBC, the impact on important and relevant patient-reported outcomes (PROs) should be determined. We systematically reviewed the NMIBC PRO literature to determine the suitability of available PRO measures (PROMs) for use in evaluating patient outcomes in NMIBC research. METHODS: We searched six electronic databases, reference lists, and key authors. Two reviewers independently applied inclusion and quality criteria and extracted findings. PROM domains, item content, and content coverage and relevance were determined for identified PROMs. Content validity was assessed against an empirically derived NMIBC-specific conceptual framework that includes 11 PRO domains and 19 sub-domains. RESULTS: Seventeen studies assessed PROs related to NMIBC and treatment impact. From these studies, 11 PROMs were identified, including three generic, three cancer-specific, and five symptom-specific. None of the PROMs cover all PRO domains important in NMIBC as assessed against our conceptual framework. The EORTC QLQ-C30 plus the NMIBC24 module was best aligned to the conceptual model, but failed to represent six outcomes important to NMIBC patients. CONCLUSIONS: Currently, some outcomes important in NMIBC are inadequately covered by generic and cancer-specific measures despite similar conceptual models. This review identified gaps in the literature regarding assessment of symptoms and other PROs considered important by NMIBC patients. Careful consideration of PROM item content is required when selecting outcome measures for use in future NMIBC clinical trials to ensure that appropriate measures are used to assess outcomes that matter to patients.

Psychometric Evaluation of a Patient-Reported Symptom Index for Nonmuscle Invasive Bladder Cancer: Field Testing Protocol.

BACKGROUND: Nonmuscle invasive bladder cancer (NMIBC) is a chronic condition requiring intensive follow-up, repeated endoscopic examinations, tumor resections, and intravesical treatments that can occur every 3 months for life. In this clinical context, patient-reported outcomes (PROs) are a critical concern for patients and their managing clinicians. PROs have enormous potential to be integral to treatment assessment and recommendations for NMIBC; however, current PRO measures are inadequate for NMIBC because they lack key NMIBC-specific symptoms and side effects associated with contemporary treatments. OBJECTIVE: The overarching aim of this study was to develop and evaluate a patient-reported symptom index (SI) for individuals with NMIBC (the NMIBC-SI) that is acceptable to patients; reliable, valid, and responsive to differences between contemporary treatments for NMIBC; and fit for purpose as an endpoint in clinical trials. METHODS: The NMIBC-SI will be evaluated in 2 field tests across a total of 3 years. Field test 1 is a cross-sectional study design involving 225 adult NMIBC patients recruited while undergoing active treatment or those who completed final treatment within the past week. Data collected include patient demographics, clinical features of the tumor, risk category, treatment type, comorbidity, and PROs. Field test 2 is a prospective longitudinal study involving 225 newly diagnosed NMIBC-SI patients. Clinical data and patient-completed questionnaires will be collected at 4 time points during treatment: before tumor resection, 1 week after resection, end-of-induction intravesical therapy, and 1-year follow-up. Standard psychometric tests will be performed to assess the reliability, validity, responsiveness, and clinical utility of the NMIBC-SI. RESULTS: Participant recruitment to field test 1 commenced in February 2017. Recruitment for field test 2 is planned to commence in January 2018. Final results are expected to be published in 2019. The NMIBC-SI will be freely available for use via registration. CONCLUSIONS: This study protocol contains detailed methods that will be used across multiple international sites. Phase 2 in the development of the NMIBC-SI will enable a comprehensive evaluation of its reliability, validity, and responsiveness to ensure that the NMIBC-SI is fit for purpose in clinical research and provides an evidence base for the ongoing improvement of future therapies for NMIBC. TRIAL REGISTRATION: ClinicalTrials.gov NCT03091764; http://clinicaltrials.gov/ct2/showNCT03091764 (Archived by WebCite at http://www.webcitation.org/6umBhQeNX).