Evidencing the impacts of health research: Insights from trials reported in the 2018 Australian Engagement and Impact Assessment

Issue Addressed: While definitions of impact may vary, they often refer to the wider benefits of research evidenced beyond academia. We evaluated case studies featuring randomised trials from the 2018 Engagement and Impact Assessment to better understand how the impacts of health research are evidenced and assessed within Australia. Methods: We collated and evaluated ‘high’ scoring case studies submitted by higher education institutions with a focus on randomised trials across all areas of health research. A qualitative coding system was used for manual content analysis to assess the key characteristics of trials reported, subsequent impacts and the methods used to evidence impacts. Results: A total of 14 case studies were identified citing 35 clinical trials. The majority of interventions were behavioural with a focus on mental, behavioural or neurodevelopmental disorders. Most trials were phase III, focused on the treatment of the indication and were funded by industry. Contribution to clinical guidelines was the highest cited research impact. While there was evidence of researchers seeking to maximise trial impact, case studies lacked details on the role of trial participants and other beneficiaries in generating impact. Conclusions: The impacts of health research can be improved through a better understanding of the priorities and agendas of funders, providing evidence of tangible impact rather than information that is contextual or predictive, and through the early development of impact strategies involving both researchers and beneficiaries. So What? Large-scale impact exercises intended for a broad range of disciplines may not be reflective of the depth and scope of health sciences research including trials

Evaluating cancer research impact: lessons and examples from existing reviews on approaches to research impact assessment

Background: Performing cancer research relies on substantial financial investment, and contributions in time and effort from patients. It is therefore important that this research has real life impacts which are properly evaluated. The optimal approach to cancer research impact evaluation is not clear. The aim of this study was to undertake a systematic review of review articles that describe approaches to impact assessment, and to identify examples of cancer research impact evaluation within these reviews. Methods: In total, 11 publication databases and the grey literature were searched to identify review articles addressing the topic of approaches to research impact assessment. Information was extracted on methods for data collection and analysis, impact categories and frameworks used for the purposes of evaluation. Empirical examples of impact assessments of cancer research were identified from these literature reviews. Approaches used in these examples were appraised, with a reflection on which methods would be suited to cancer research impact evaluation going forward. Results: In total, 40 literature reviews were identified. Important methods to collect and analyse data for impact assessments were surveys, interviews and documentary analysis. Key categories of impact spanning the reviews were summarised, and a list of frameworks commonly used for impact assessment was generated. The Payback Framework was most often described. Fourteen examples of impact evaluation for cancer research were identified. They ranged from those assessing the impact of a national, charity-funded portfolio of cancer research to the clinical practice impact of a single trial. A set of recommendations for approaching cancer research impact assessment was generated. Conclusions: Impact evaluation can demonstrate if and why conducting cancer research is worthwhile. Using a mixed methods, multi-category assessment organised within a framework, will provide a robust evaluation, but the ability to perform this type of assessment may be constrained by time and resources. Whichever approach is used, easily measured, but inappropriate metrics should be avoided. Going forward, dissemination of the results of cancer research impact assessments will allow the cancer research community to learn how to conduct these evaluations

Creation of the first national linked colorectal cancer dataset in Scotland:prospects for future research and a reflection on lessons learned

Introduction: Current understanding of cancer patients, their treatment pathways and outcomes relies mainly on information from clinical trials and prospective research studies representing a selected sub-set of the patient population. Whole-population analysis is necessary if we are to assess the true impact of new interventions or policy in a real-world setting. Accurate measurement of geographic variation in healthcare use and outcomes also relies on population-level data. Routine access to such data offers efficiency in research resource allocation and a basis for policy that addresses inequalities in care provision. Objective: Acknowledging these benefits, the objective of this project was to create a population level dataset in Scotland of patients with a diagnosis of colorectal cancer (CRC). Methods: This paper describes the process of creating a novel, national dataset in Scotland. Results: In total, thirty two separate healthcare administrative datasets have been linked to provide a comprehensive resource to investigate the management pathways and outcomes for patients with CRC in Scotland, as well as the costs of providing CRC treatment. This is the first time that chemotherapy prescribing and national audit datasets have been linked with the Scottish Cancer Registry on a national scale. Conclusions: We describe how the acquired dataset can be used as a research resource and reflect on the data access challenges relating to its creation. Lessons learned from this process and the policy implications for future studies using administrative cancer data are highlighted

Treatment of newly diagnosed glioblastoma in the elderly

This is a protocol for a Cochrane Review (Intervention). The objectives are as follows: To determine the most effective and best‐tolerated approaches for the treatment of elderly people with newly diagnosed glioblastoma. To summarise current evidence for the incremental resource use, utilities, costs and cost‐effectiveness associated with the different management strategies for newly diagnosed glioblastoma among adults aged over 70 years

Immune checkpoint inhibition as a strategy in the neoadjuvant treatment of locally advanced rectal cancer

The treatment of locally advanced rectal cancer (LARC) has seen major advances over the past 3 decades, with multimodality treatment now standard of care. Combining surgical resection with radiotherapy and/or chemotherapy can reduce local recurrence from around 20% to approximately 5%. Despite improvements in local control, distant recurrence and subsequent survival rates have not changed. Immune checkpoint inhibitors have improved patient outcomes in several solid tumor types in the neoadjuvant, adjuvant, and advanced disease setting; however, in colorectal cancer, most clinical trials have been performed in the metastatic setting and the benefits confined to microsatellite instability–high tumors. In this article, we review the current preclinical and clinical evidence for using immune checkpoint inhibition in the treatment of LARC and discuss the rationale for specifically exploring the use of this therapy in the neoadjuvant setting. We summarize and discuss relevant clinical trials that are currently in setup and recruiting to test this treatment strategy and reflect on unanswered questions that still need to be addressed within future research efforts

Young Children’s Mental Well-Being in Low-Income South African Settings: A Qualitative Study

This qualitative study aimed to capture community perspectives of the risks and protective factors for social emotional development and mental health of young children in low-income South Africa settings, and was conducted as one component of a larger study with the ultimate aim of co-designing the Mazi Umntanakho (‘know your child’) digital tool. Twenty focus group discussions (n = 154, 97% female) were held with staff of community-based organisations (CBOs) and community health worker (CHW) programmes in urban and rural sites from four geographical regions. Data were analysed thematically, and grouped according to components of nurturing care (responsive caregiving, safety and security, good health, adequate nutrition, opportunities for early learning) and risk and protective factors. Risks reported by participants far outweighed protective factors, and the most dominant theme identified was risks associated with responsive caregiving from CBO and CHW perspectives. These related to participants’ perceptions of caregivers’ attitudes, knowledge, beliefs, behaviours, and challenges not conducive to the provision of responsive caregiving. The most commonly perceived risks to safety and security were substance abuse, along with economic challenges, neglect, abuse and violence. Basic needs not being met was reported as the main risk to adequate nutrition and good health, followed by insufficient services. Limited resources and caregivers’ limited education and literacy were perceived to be risks to early learning. These findings highlight the urgent need to mitigate risks and amplify protective factors for the social emotional development and mental health of young children in South Africa. It is critical that these are considered within the contextual realities of low-income communities

Clinician attitudes to using low dose radiotherapy to treat COVID-19 lung disease

Introduction: Current treatments for COVID-19 lung disease have limited efficacy. Low dose radiotherapy (LDRT) has received both interest and criticism as a potential treatment for this condition. In this qualitative study we explored clinicians’ perspectives in order to identify barriers to testing LDRT in clinical trials and implementing it in clinical practice. Methods: Semi-structured interviews were undertaken with six clinicians from three medical disciplines. Interviews were recorded, transcribed verbatim and analysed thematically, using a framework approach. Common themes regarding barriers to using LDRT for COVID-19 lung disease were identified from the data. Results: Three categories of barriers emerged: i) the potential to do harm to the patient, including difficulty in predicting harm and lack of existing data to inform quantification of risks; ii) the feasibility of trialling this novel treatment strategy in the clinical setting, in particular patient selection and buy-in from relevant clinician groups; and iii) the logistics of delivering the treatment, in particular risks of transmission to other patients and resources required for patient transfer. Conclusions: This study identified several barriers that may impede the evaluation and subsequent implementation of LDRT as a treatment for COVID-19 lung disease, from the perspectives of clinicians in three relevant specialties. By documenting and articulating these concerns, we hope to enhance discussion of why these barriers exist, and enable them to be addressed in a proactive manner in order to facilitate research into the potential benefits of radiation treatment for patients with COVID-19 lung disease

A Phase 2b randomised, controlled, partially blinded trial of the HIV Nucleoside Reverse Transcriptase Inhibitor BMS-986001 (AI467003): Weeks 24 and 48 Efficacy, Safety, Bone and Metabolic Results

Background BMS-986001 is a thymidine analogue nucleoside reverse transcriptase inhibitor (NRTI) designed to maintain in-vitro antiviral activity while minimising off-target effects. We assessed the efficacy and safety of BMS-986001 versus tenofovir disoproxil fumarate in treatment-naive patients with HIV-1. Methods In this phase 2b, randomised, active-controlled trial (AI467003), we recruited treatment-naive (no current or previous exposure to an antiretroviral drug for >1 week) adults (aged at least 18 years) with HIV-1 from 47 sites across Asia, Australia, Europe, North America, South Africa, and South America. Patients with plasma HIV-1 RNA greater than 5000 copies per mL and CD4 counts greater than 200 cells per μL were randomly assigned (2:2:2:3) to receive BMS-986001 100 mg, 200 mg, or 400 mg once a day or to receive tenofovir disoproxil fumarate 300 mg once a day; each allocation was given with efavirenz 600 mg once a day and lamivudine 300 mg once a day. Both patients and investigators were masked to BMS-986001 dose (achieved with similar looking placebo tablets), but not allocation up to and including week 48. The primary endpoints were the proportion of patients with plasma HIV-1 RNA less than 50 copies per mL and safety events (serious adverse events and adverse events leading to discontinuation) through week 24; the main analysis was with a modified intention-to-treat population. Resistance analysis was a secondary endpoint, and additional safety parameters were exploratory endpoints. This trial is registered with ClinicalTrials.gov, number NCT01489046, and the European Clinical Trials Database, number EudraCT 2011-003329-89. Findings Patients were recruited between Jan 25, 2012, and Oct 3, 2012; 757 patients were assessed for eligibility and 301 were randomly assigned to receive either BMS-986001 once a day (67 patients to 100 mg, 67 to 200 mg, and 66 to 400 mg) or tenofovir disoproxil fumarate (n=101). 297 patients received at least one dose of study drug. At week 24, 57 (88%) of 65 patients for whom there were data in the 100 mg group, 54 (81%) of 67 in the 200 mg group, 62 (94%) of 66 in the 400 mg group achieved HIV-1 RNA less than 50 copies per mL, compared with 88 (89%) of 99 in the tenofovir disoproxil fumarate group (modified intention-to-treat population). BMS-986001 was generally well tolerated through week 48. Two patients had BMS-986001-related serious adverse events (atypical drug eruption and thrombocytopenia) and two in the tenofovir disoproxil fumarate group had study drug-related serious adverse events (potential drug-induced liver injury and depression or lipodystrophy) that led to discontinuation. NRTI resistance-associated mutations were reported in four (2%) of 198 patients, and non-NRTI mutations in 17 (9%) of 198 patients receiving BMS-986001 versus none of 99 and one (1%) of 99 patients receiving tenofovir disoproxil fumarate, respectively. Compared with tenofovir disoproxil fumarate, individuals in the BMS-986001 groups showed a smaller decrease in lumbar spine and hip bone mineral density but greater accumulation of limb and trunk fat, subcutaneous and visceral adipose tissue, and increased total cholesterol. Interpretation BMS-986001 had similar efficacy to that of tenofovir disoproxil fumarate and was associated with a smaller decrease in bone mineral density; however, greater resistance and gains in both peripheral and central fat accumulation were recorded for the investigational drug. Bristol-Myers Squibb has discontinued its involvement in the development of BMS-986001, and future decisions on development will be made by Oncolys BioPharma