What guidance exists to support patient partner compensation practices? A scoping review of available policies and guidelines.

BACKGROUND: An integral aspect of patient engagement in research, also known as patient and public involvement, is appropriately recognising patient partners for their contributions through compensation (e.g., coauthorship, honoraria). Despite known benefits to compensating patient partners, our previous work suggested compensation is rarely reported and researchers perceive a lack of guidance on this issue. To address this gap, we identified and summarised available guidance and policy documents for patient partner compensation. METHODS: We conducted this scoping review in accordance with methods suggested by the JBI. We searched the grey literature (Google, Google Scholar) in March 2022 and Overton (an international database of policy documents) in April 2022. We included articles, guidance or policy documents regarding the compensation of patient partners for their research contributions. Two reviewers independently extracted and synthesised document characteristics and recommendations. RESULTS: We identified 65 guidance or policy documents. Most documents were published in Canada (57%, n = 37) or the United Kingdom (26%, n = 17). The most common recommended methods of nonfinancial compensation were offering training opportunities to patient partners (40%, n = 26) and facilitating patient partner attendance at conferences (38%, n = 25). The majority of guidance documents (95%) suggested financially compensating (i.e., offering something of monetary value) patient partners for their research contributions. Across guidance documents, the recommended monetary value of financial compensation was relatively consistent and associated with the role played by patient partners and/or specific engagement activities. For instance, the median monetary value for obtaining patient partner feedback (i.e., consultation) was $19/h (USD) (range of $12-$50/h). We identified several documents that guide the compensation of specific populations, including youth and Indigenous peoples. CONCLUSION: Multiple publicly available resources exist to guide researchers, patient partners and institutions in developing tailored patient partner compensation strategies. Our findings challenge the perception that a lack of guidance hinders patient partner financial compensation. Future efforts should prioritise the effective implementation of these compensation strategies to ensure that patient partners are appropriately recognised. PATIENT OR PUBLIC CONTRIBUTIONS: The patient partner coauthor informed protocol development, identified data items, and interpreted findings.

Clinical and Economic Value of a Biosimilar Portfolio to Stakeholders: An Integrative Literature Review.

Purpose: While the value of individual biosimilars is evident, little is known about the value of a biosimilar portfolio beyond the cost savings between biosimilars and originators. Stakeholders may consider the value of a manufacturer's biosimilar portfolio, especially when negotiating portfolio-based contracts or other rebate programs. However, little is known about what other types of value, in addition to financial benefits, decision-makers perceive regarding a manufacturer with a biosimilar portfolio compared to those without one. The objective of this integrative literature review was to describe a conceptual framework consisting of themes that may help define the value of a biosimilar portfolio. Methods: An integrative literature review was conducted using Excerpta Medica Database (Embase) and Medical Literature Analysis and Retrieval System Online (MEDLINE). Grey literature searches of search engines, journals not indexed in Embase or MEDLINE, healthcare payers, health technology assessment bodies, value frameworks, and non-pharmaceutical industry analogs were also conducted. Eligible studies reported on the value of a biosimilar portfolio in decision-making by stakeholders. Apart from the literature, insights were gained from clinical experience and observation. Results: No studies investigating biosimilar portfolio value were identified; however, several themes were identified that may help define the value of a biosimilar portfolio: Manufacturing; procurement, inventory, and storage; administration; education; and transaction costs. Several non-pharmaceutical industry analogs were identified: Product line length and single-supplier versus multiple-supplier procurement. Several themes were identified through other sources: Science credibility and research. Based on these themes, we developed a conceptual framework for biosimilar portfolio value. Conclusion: To our knowledge, this is the first study to systematically assess and create a framework for biosimilar portfolio value. The conceptual framework described here could be tested to quantify the clinical and economic value associated with a biosimilar portfolio.

Though the value of single biosimilars is evident, little is known about the value of a biosimilar portfolio beyond the cost savings incurred between biosimilars and originators.We identified seven themes that may help to define the value of a biosimilar portfolio: Manufacturing; procurement, inventory, and storage; administration; education; transaction costs; science credibility; and research.These themes may be integrated into a conceptual framework that may form a basis to help quantify the clinical and economic benefit of a biosimilar portfolio to stakeholders.

Clinical outcomes for previously treated patients with advanced biliary tract cancer: a meta-analysis.

Aim: A systematic review and meta-analysis were performed to evaluate the efficacy of treatments for previously treated advanced biliary tract cancer (BTC) patients. Materials & methods: Databases were searched for studies evaluating treatments for advanced (unresectable and/or metastatic) BTC patients who progressed on prior therapy. Pooled estimates of objective response rate (ORR), median overall survival (OS) and median progression-free survival (PFS) were calculated using random effects meta-analysis. Results: Across 31 studies evaluating chemotherapy or targeted treatment regimens in an unselected advanced BTC patient population, pooled ORR was 6.9%, median OS was 6.6 months and median PFS was 3.2 months. Conclusion: The efficacy of conventional treatments for previously treated advanced BTC patients is poor and could be improved by novel therapies.

What is this article about? Most patients with biliary tract cancer are identified with advanced disease, and almost all go through a worsening of the disease after their first treatment. For patients who go on to receive their next treatment, current guidelines are unclear regarding the best treatment choice. Therefore, we examined the available medical literature and performed an analysis of multiple studies to calculate overall estimates of the clinical value of standard treatments for these patients. Our goal was to develop a benchmark against which to compare the clinical value of new treatments that are currently being assessed in clinical trials. What were the results? We identified 31 studies assessing standard treatments (involving chemotherapy or molecularly targeted treatments) in previously treated advanced biliary tract cancer patients. Across these studies, the objective tumor response rate was 6.9%, median overall survival was 6.6 months and median progression-free survival was 3.2 months. What do the results of the study mean? These results indicate that there is limited clinical value of standard treatments for patients with advanced biliary tract cancer whose disease worsened after first treatment. This medical need could potentially be met by new treatments, such as immunotherapies that restore the immune system's ability to attack cancer cells and thereby prolong patient survival.

Investigating Citizens' Acceptance of Contact Tracing Apps: Quantitative Study of the Role of Trust and Privacy.

BACKGROUND: The COVID-19 pandemic accelerated the need to understand citizen acceptance of health surveillance technologies such as contact tracing (CT) apps. Indeed, the success of these apps required widespread public acceptance and the alleviation of concerns about privacy, surveillance, and trust. OBJECTIVE: This study aims to examine the factors that foster a sense of trust and a perception of privacy in CT apps. Our study also investigates how trust and perceived privacy influence citizens' willingness to adopt, disclose personal data, and continue to use these apps. METHODS: Drawing on privacy calculus and procedural fairness theories, we developed a model of the antecedents and behavioral intentions related to trust and privacy perceptions. We used structural equation modeling to test our hypotheses on a data set collected at 2 time points (before and after the launch of a national CT app). The sample consisted of 405 Irish residents. RESULTS: Trust in CT apps was positively influenced by propensity to trust technology (ß=.074; P=.006), perceived need for surveillance (ß=.119; P<.001), and perceptions of government motives (ß=.671; P<.001) and negatively influenced by perceived invasion (ß=-.224; P<.001). Perceived privacy was positively influenced by trust (ß=.466; P<.001) and perceived control (ß=.451; P<.001) and negatively influenced by perceived invasion (ß=-.165; P<.001). Prelaunch intentions toward adoption were influenced by trust (ß=.590; P<.001) and perceived privacy (ß=.247; P<.001). Prelaunch intentions to disclose personal data to the app were also influenced by trust (ß=.215; P<.001) and perceived privacy (ß=.208; P<.001) as well as adoption intentions before the launch (ß=.550; P<.001). However, postlaunch intentions to use the app were directly influenced by prelaunch intentions (ß=.530; P<.001), but trust and perceived privacy only had an indirect influence. Finally, with regard to intentions to disclose after the launch, use intentions after the launch (ß=.665; P<.001) and trust (ß=.215; P<.001) had a direct influence, but perceived privacy only had an indirect influence. The proposed model explained 74.4% of variance in trust, 91% of variance in perceived privacy, 66.6% of variance in prelaunch adoption intentions, 45.9% of variance in postlaunch use intentions, and 83.9% and 79.4% of variance in willingness to disclose before the launch and after the launch, respectively. CONCLUSIONS: Positive perceptions of trust and privacy can be fostered through clear communication regarding the need and motives for CT apps, the level of control citizens maintain, and measures to limit invasive data practice. By engendering these positive beliefs before launch and reinforcing them after launch, citizens may be more likely to accept and use CT apps. These insights are important for the launch of future apps and technologies that require mass acceptance and information disclosure.

BioCanRx Summit for Cancer Immunotherapy 2022 Proceedings.

From 19 to 21 November 2022, BioCanRx held its first post-pandemic in-person Summit for Cancer Immunotherapy in Montreal, Canada. The meeting was well attended by patients, trainees, researchers, clinicians, and industry professionals, who came together to discuss the current state and future of biotherapeutics for cancer in Canada and beyond. Three plenaries, three keynote speakers, a lively debate, and panel discussions, together with poster sessions and a social event, made the event memorable and productive. The current state of cellular therapies, cellular engineering, clinical trials, and the role of the cancer microbiome were discussed in plenary session, and the patient voice was welcomed and present throughout the meeting, in large part due to the Learning Institute, a BioCanRx initiative to include patient partners in research. In this meeting review, we highlight the platform presentations, keynote speakers, debate combatants, panellists, and the patient perspective on the annual meeting.

Prevalence of patient partner authorship and acknowledgment in child health research publications: an umbrella review.

OBJECTIVES: Children and families are increasingly involved as equal partners in child health research, however, considerations around authorship have received little attention and there is limited guidance on the topic. Our objective was to determine the frequency and nature of patient partner authorship and/or acknowledgment among articles focused on patient engagement in child health research. STUDY DESIGN AND SETTING: In this umbrella review, we searched MEDLINE, Embase, APA PsycINFO, Cochrane Database of Systematic Reviews, CINAHL, and Web of Science for systematic/scoping reviews on patient engagement in child health research. Individual articles included in eligible reviews comprised the sample of articles for analysis and were examined to identify patient partner authorship. Descriptive statistics were used to quantify patient partner authorship and/or acknowledgment and to summarize article characteristics. RESULTS: Twelve systematic/scoping reviews met eligibility criteria, from which 230 individual articles were examined. In 16/230 (7%) articles, there was at least one patient partner author, and in 6/230 (3%) articles, patient partners were included as group authors. Within article Acknowledgments sections, patient partners were acknowledged by name in 41/230 (18%) articles, and anonymously or as a group in 98/230 (43%) articles. Patient partner authorship and/or acknowledgment was more frequent among articles published more recently (after 2015) and among articles where patient engagement was explicitly reported in the article. CONCLUSION: Patient partners were more likely to be acknowledged than listed as an author on articles on patient engagement in child health research. Understanding patient partner preferences about authorship and acknowledgment, examination of the unique aspects of child and youth authorship and developing supports to empower patient partner authorship are needed.

Recognizing patient partner contributions to health research: a systematic review of reported practices.

BACKGROUND: Patient engagement in research refers to collaboration between researchers and patients (i.e., individuals with lived experience including informal caregivers) in developing or conducting research. Offering non-financial (e.g., co-authorship, gift) or financial (e.g., honoraria, salary) compensation to patient partners can demonstrate appreciation for patient partner time and effort. However, little is known about how patient partners are currently compensated for their engagement in research. We sought to assess the prevalence of reporting patient partner compensation, specific compensation practices (non-financial and financial) reported, and identify benefits, challenges, barriers and enablers to offering financial compensation. METHODS: We conducted a systematic review of studies citing the Guidance for Reporting the Involvement of Patients and the Public (GRIPP I and II) reporting checklists (October 2021) within Web of Science and Scopus. Studies that engaged patients as research partners were eligible. Two independent reviewers screened full texts and extracted data from included studies using a standardized data abstraction form. Data pertaining to compensation methods (financial and non-financial) and reported barriers and enablers to financially compensating patient partners were extracted. No formal quality assessment was conducted since the aim of the review is to describe the scope of patient partner compensation. Quantitative data were presented descriptively, and qualitative data were thematically analysed. RESULTS: The search identified 843 studies of which 316 studies were eligible. Of the 316 studies, 91% (n = 288) reported offering a type of compensation to patient partners. The most common method of non-financial compensation reported was informal acknowledgement on research outputs (65%, n = 206) and co-authorship (49%, n = 156). Seventy-nine studies (25%) reported offering financial compensation (i.e., honoraria, salary), 32 (10%) reported offering no financial compensation, and 205 (65%) studies did not report on financial compensation. Two key barriers were lack of funding to support compensation and absence of institutional policy or guidance. Two frequently reported enablers were considering financial compensation when developing the project budget and adequate project funding. CONCLUSIONS: In a cohort of published studies reporting patient engagement in research, most offered non-financial methods of compensation to patient partners. Researchers may need guidance and support to overcome barriers to offering financial compensation.

The term patient engagement in research is used to describe research that is conducted "with" patients, rather than "on" patients. It is important that researchers recognize patient partners for their time and expertise. In order to gain a better understanding of approaches to recognition for patient partners we reviewed published studies to: (1) assess how often financial compensation is reported, (2) identify how patient partners are reported as being compensated, and (3) understand what benefits, challenges, barriers and enablers might exist to offering financial compensation. We conducted a systematic review of articles citing the Guidance for Reporting the Involvement of Patients and the Public (GRIPP) guidelines. We included all study designs if patients were engaged as partners. Studies in which patients were participants only were excluded. Data collected included information about details of patient partner compensation (financial and non-financial practices) as well as challenges relating to financial compensation. Numerical data were analysed descriptively. Textual data were coded by two reviewers and collated into overarching themes. Our search identified 316 papers. Of these, 91% reported offering compensation to patient partners. Most common methods were acknowledgement (65%) and co-authorship (49%). Only 79 studies (25%) reported offering financial compensation to patient partners. Limited funding and lack of institutional guidance were identified as two key barriers that may be preventing researchers from offering financial compensation. Our review found that non-financial methods of compensation are reported more often than financial compensation. Researchers may require more support when offering financial compensation to patient partners.

Diagnostic test accuracy of screening tools for post-traumatic stress disorder among refugees and asylum seekers: A systematic review and meta-analysis.

Background: Refugees and asylum seekers often experience traumatic events resulting in a high prevalence of post-traumatic stress disorder (PTSD). Undiagnosed PTSD can have detrimental effects on resettlement outcomes. Immigration medical exams provide an opportunity to screen for mental health conditions in refugee and asylum seeker populations and provide links to timely mental health care. Objective: To assess the diagnostic accuracy of screening tools for PTSD in refugee and asylum seeker populations. Methods: We systematically searched Medline, Embase, PsycINFO, CENTRAL and CINAHL up to 29 September 2022. We included cohort-selection or cross-sectional study designs that assessed PTSD screening tools in refugee or asylum seeker populations of all ages. All reference standards were eligible for inclusion, with a clinical interview considered the gold standard. We selected studies and extracted diagnostic test accuracy data in duplicate. Risk of bias and applicability concerns were addressed using QUADAS-2. We meta-analyzed findings using a bivariate random-effects model. We partnered with a patient representative and a clinical psychiatrist to inform review development and conduct. Results: Our review includes 28 studies (4,373 participants) capturing 16 different screening tools. Nine of the 16 tools were developed specifically for refugee populations. Most studies assessed PTSD in adult populations, but three included studies focused on detecting PTSD in children. Nine studies looked at the Harvard Trauma Questionnaire (HTQ) with diagnostic cut-off points ranging from 1.17 to 2.5. Meta-analyses revealed a summary point sensitivity of 86.6% (95%CI 0.791; 0.917) and specificity of 78.9% (95%CI 0.639; 0.888) for these studies. After evaluation, we found it appropriate to pool other screening tools (Posttraumatic Stress Disorder Checklist, the Impact of Event Scale, and the Posttraumatic Diagnostic Scale) with the HTQ. The area under the curve for this model was 79.4%, with a pooled sensitivity of 86.2% (95%CI 0.759; 0.925) and a specificity of 72.2% (95%CI 0.616; 0.808). Conclusions: Our review identified several screening tools that perform well among refugees and asylum seekers, but no single tool was identified as being superior. The Refugee Health Screener holds promise as a practical instrument for use in immigration medical examinations because it supports the identification of PTSD, depression, and anxiety across diverse populations. Future research should consider tool characteristics beyond sensitivity and specificity to facilitate implementation in immigration medical exams. Registration: Open Science Framework: 10.17605/OSF.IO/PHNJV.

The impact of patient engagement on trials and trialists in Ontario, Canada: An interview study with IMPACT awardees.

BACKGROUND: A key component of patient-oriented research is the engagement of patients as partners in the design and conduct of health research. While there is now national infrastructure and networks to support the engagement of patients as partners, there remain calls for promising practices and success stories. In particular, there remains a keen interest in evaluating the impact that patient engagement has on health research studies. We aimed to investigate the impact that patient engagement had on health research conducted in Ontario, Canada. METHODS: Our sampling frame was studies that were awarded funding by the Ontario SPOR SUPPORT Unit. Semi-structured interviews were conducted with 10 principal investigators, members of research teams, and patient partners. Interviews explored the role of patient partners, the perceived impact of the patient engagement on the study, challenges faced, and advice for other researchers considering patient engagement. Data were analysed using the thematic analysis method with transcripts coded independently by two members of the study team. All coding and subsequent theme generation were discussed until consensus was achieved. RESULTS: There was variation in the methods used to engage patients and other stakeholders, the roles that patients and stakeholders occupied, and where they had input. Interviewees discussed two major areas of impact of patient engagement on research: impact on the study about which they were being interviewed, which tended to relate to improved relevancy of the research to the study population, and impact on themselves which led to changes in their own practice or approaches to future research. Identified challenges to patient engagement included: identifying and reaching patient advisors or patient partners, time-related challenges, and maintaining engagement over the course of the research. CONCLUSIONS: There remains a need to further build out the concept of relevancy and how it may be operationalised in practice. Further, the longer-term impacts of patient engagement on researchers and research teams remains under-explored and may reveal additional elements for evaluation. Challenges to patient engagement remain, including identifying and maintaining engagement with partners that reflect the diversity of the population of interest.

We interviewed 10 individuals associated with studies that were funded through the Ontario Strategy for Patient Oriented Research (SPOR) Unit. We asked them about how they had engaged patients, families or caregivers in their study, how this engagement had influenced their study, the challenges they faced, and advice for other researchers considering engaging with patients, families and caregivers. We found that patients had been engaged in a variety of ways and at different times. The changes brought about by the patient engagement varied between studies but tended to reflect an improvement in how relevant the study was to patients. Researchers also shared how engagement with patients, families, and caregivers had changed their approaches to future research. Key challenges facing researchers included finding partners that were appropriate for the study, as well making sure that the approach to engagement overcame issues such as financial or logistical barriers that could prevent patients, families or caregivers from partnering with the study.

Recognizing patient partner contributions to health research: a mixed methods research protocol.

BACKGROUND: The overall aim of this program of research is to assess when/how patient partners are compensated financially for their contributions to health research. The research program consists of three studies to address the following questions: (1) What is the prevalence of reporting patient partner financial compensation? (2) What are researcher and institutional attitudes around patient partner financial compensation? (3) What are the current practices of patient partner financial compensation and what guidance exists to inform these practices? METHODS: In our first project, we will conduct a systematic review to assess the prevalence of reporting patient partner financial compensation and identify current financial compensation practices on an international scale. We will identify a cohort of published studies that have engaged patients as partners through a forward citation search of the Guidance for Reporting the Involvement of Patients and the Public (GRIPP I and II) checklists. We will extract details of financial compensation (type of financial compensation, amount, payment frequency etc.) and reported benefits, challenges, barriers and enablers to financially compensating patient partners. Quantitative data will be analyzed descriptively, and qualitative data will undergo thematic analysis. In our second project, we will conduct a cross-sectional survey of researchers who have engaged patient partners. We will also survey members of their affiliated institutions to gain further understanding of stakeholder experiences and attitudes with patient partner financial compensation. Survey responses will be analyzed by calculating prevalence. In our third project, we will conduct a scoping review to identify all published guidance and policy documents that guide patient partner financial compensation. Overton, the largest available online database of international policy documents, and the grey literature will be systematically searched. Data items will be extracted and presented descriptively. A comprehensive overview of guidance documents will be presented, which will represent a repository of resources that stakeholders can refer to when developing a financial compensation strategy. DISCUSSION: Our three studies will not only inform and assist patient partners and researchers by informing compensation strategies, but also support the inclusion of diverse perspectives. We will disseminate findings through traditional mediums (publications, conferences) as well as social media, non-technical summaries, and visual abstracts.

BACKGROUND: Partnering with patients, caregivers and members of the public to co-develop and co-conduct research is becoming more accepted and prevalent. However, it is unclear how researchers recognize patient partners for their contributions to research projects. In this publication we outline a series of three studies that will help us better understand when and how patient partners are being financially compensated for their involvement. METHODS: First, we will conduct a review of the literature to identify an international group of researchers that engage patients as research partners. Evaluating these studies will give us an idea about how often patient partners are compensated, and the methods of compensation being used (e.g. offered gifts, cash, etc.). Second, we will survey researchers and institutions who have experience with patient engagement to ask them for more details about their experiences with patient partner compensation (i.e. challenges that they have encountered and their attitudes). Third, we will conduct another review to identify any guidance documents or policies that can help guide researchers through the processes of financially compensating patient partners. We will provide a summary of all of these guidance documents so that researchers, patient partners, and institutions have a one-stop-shop of resources. DISCUSSION: We hope that our three studies will inform and help researchers and patient partners navigate the processes for compensating patient engagement in research.

Building a Platform for Meaningful Patient Partnership to Accelerate "Bench-to-Bedside" Translation of Promising New Therapies.

Engaging patients as partners in the design and execution of early-phase clinical trials offers a unique opportunity to ensure patient perspectives are considered. Here we describe our experience partnering with four individuals with lived experience of blood cancer to co-develop documents and services to support participants of an early-phase trial. Through regular team meetings, patient partners co-developed a visual informed consent document and a non-technical summary of the informed consent document to facilitate participant understanding of trial procedures. Overall, patient partners highlighted important trial components that would not have been identified without their input.

Economic and Humanistic Burden of Triple-Negative Breast Cancer: A Systematic Literature Review.

BACKGROUND: Triple-negative breast cancer (TNBC) accounts for 10-20% of all breast cancers (BCs). It is more commonly diagnosed in younger women and often has a less favorable prognosis compared with other BC subtypes. OBJECTIVE: The objective of this study was to provide a literature-based extensive overview of the economic and humanistic burden of TNBC to assist medical decisions for healthcare payers, providers, and patients. METHODS: A systematic literature review was performed using multiple databases, including EMBASE, MEDLINE, Econlit, the Cochrane Central Register of Controlled Trials, and the Cochrane Database of Systematic Reviews, from database inception to 16 May 2021. In addition, a targeted search was performed in the Northern Light Life Sciences Conference Abstracts database from 2016 through June 2021. The bibliographies of included articles were reviewed to identify other potentially relevant publications. Quality assessment of the included studies was conducted. RESULTS: The review identified 19 studies assessing the economic burden and 10 studies assessing the humanistic burden of TNBC. Studies varied widely in study design, settings, patient populations, and time horizons. The estimates of mean per-patient annual direct medical costs ranged from around $20,000 to over $100,000 in stage I-III TNBC and from $100,000 to $300,000 in stage IV TNBC. Healthcare costs and resource utilization increased significantly with disease recurrence, progression, and increased cancer stage or line of therapy. Compared with the costs of systemic anticancer therapy, cancer management costs comprised a larger portion of total direct costs. The estimates of indirect costs due to productivity loss ranged from $207 to $1573 per patient per month (all costs presented above were adjusted to 2021 US dollars). Cancer recurrence led to significantly reduced productivity and greater rates of leaving the workforce. A rapid deterioration of health utility associated with disease progression was observed in TNBC patients. Treatment with pembrolizumab or talazoparib showed significantly greater improvements in health-related quality of life (HRQoL) compared with chemotherapy, as measured by EORTC QLQ-C30, QLQ-BR23, and FACT-B. CONCLUSION: TNBC is associated with a substantial economic burden on healthcare systems and societies and considerably reduced productivity and HRQoL for patients. This study synthesized the published literature on the economic and humanistic burden of TNBC and highlighted the need for continued research due to the rapidly changing landscape of TNBC care.

Patient engagement in preclinical laboratory research: A scoping review.

BACKGROUND: 'Patient engagement' involves meaningful collaboration between researchers and 'patient partners' to co-create research. It helps ensure that research being conducted is relevant to its ultimate end-users. Although patient engagement within clinical research has been well documented, the prevalence and effects of patient engagement in translational preclinical laboratory research remain unclear. The aim of this scoping review is to present current patient engagement activities reported in preclinical laboratory research. METHODS: MEDLINE, Embase, and grey literature were systematically searched from inception to April 2021. Studies that described or investigated patient engagement in preclinical laboratory research were included. Patient engagement activities where patients (i.e. patients, family members, caregivers or community members) provided input, or consultation on at least one element of the research process were eligible for inclusion. Study characteristics and outcomes were extracted and organized thematically. FINDINGS: 32 reports were included (30 primary studies, 1 narrative review, and 1 researcher guide). Most studies engaged patients at the education or priority setting stages (n=26). The most frequently reported benefit of patient engagement was 'providing a mutual learning opportunity'. Reported barriers to patient engagement reflected concerns around 'differences in knowledge and research experience' and how this may challenge communication and limit meaningful collaboration. INTERPRETATION: Patient engagement is feasible and beneficial for preclinical laboratory research. Future work should focus on assessing the impacts of patient engagement in this area of research. FUNDING: None.

Epidemiology and reporting characteristics of preclinical systematic reviews.

In an effort to better utilize published evidence obtained from animal experiments, systematic reviews of preclinical studies are increasingly more common-along with the methods and tools to appraise them (e.g., SYstematic Review Center for Laboratory animal Experimentation [SYRCLE's] risk of bias tool). We performed a cross-sectional study of a sample of recent preclinical systematic reviews (2015-2018) and examined a range of epidemiological characteristics and used a 46-item checklist to assess reporting details. We identified 442 reviews published across 43 countries in 23 different disease domains that used 26 animal species. Reporting of key details to ensure transparency and reproducibility was inconsistent across reviews and within article sections. Items were most completely reported in the title, introduction, and results sections of the reviews, while least reported in the methods and discussion sections. Less than half of reviews reported that a risk of bias assessment for internal and external validity was undertaken, and none reported methods for evaluating construct validity. Our results demonstrate that a considerable number of preclinical systematic reviews investigating diverse topics have been conducted; however, their quality of reporting is inconsistent. Our study provides the justification and evidence to inform the development of guidelines for conducting and reporting preclinical systematic reviews.

Partnering with patients to get better outcomes with chimeric antigen receptor T-cell therapy: towards engagement of patients in early phase trials.

AIM: Though patient engagement in clinical research is growing, recent reports suggest few clinical trials report on such activities. To address this gap, we describe our approach to patient engagement in the development of a clinical trial protocol to assess a new immunotherapy for blood cancer (chimeric antigen receptor T-cell therapy, CAR-T cell therapy). METHODS: Our team developed a clinical trial protocol by working with patient partners from inception. Two patient partners with lived blood cancer experience were identified through referrals from our team's professional network and patient organization contacts. Our patient partners were onboarded to the team and engaged in several studies conducted to develop the clinical trial protocol, including a systematic review of the existing literature on the therapy, patient interviews and a survey to obtain perspectives on barriers and enablers to participating in the trial, an early economic analysis, and a retrospective cohort study. RESULTS: Engaging patient partners enhanced our research in ways that would not have otherwise occurred. By selecting patient important outcomes for data collection, our partners helped flag that quality of life and health utility measures have not been reported in previous CAR-T cell therapy trials for blood cancer. Our partners also co-developed a non-technical summary of the systematic review that summarized results in an accessible manner. Our patient partners reviewed interview and survey questions, to improve the language and appropriateness; provided recruitment suggestions; and provided a patient perspective on the results, thereby confirming the importance of findings. Input was also obtained on costs for the early economic analysis. Our patient partners identified costs that may be a burden to both patients and caregivers during a trial and helped to confirm that the overall structure of the economic model reflected the patient care pathway. Our patient partners also shared their diagnosis and treatment stories, which helped to provide the research team with insight into this experience. CONCLUSIONS: Contributions by our patient partners were invaluable to each component study, as well as the overall development of the trial protocol. We plan to use this approach in the future in order to meaningfully engage patients in the development of other clinical trials; we also hope that by reporting our methods this will help other research teams to do the same. TRIAL REGISTRATION: Affiliated with the development of NCT03765177.

Are we on the same page? Exploring stakeholders' shared mental models of mobile health in rural Nigeria.

Despite the benefits promised by mobile health, the introduction of these solutions is often met with resistance from various stakeholders. This article adopts a shared mental model approach to unearth the current perceptions, concerns, and mentalities of key stakeholders engaged in the provision of healthcare in Nigeria. These include policy makers, academics, healthcare professionals, and health information systems developers. Interviews and focus groups were used to examine stakeholders' views across three mental models: (1) the technology, (2) processes, and (3) the team. Our investigations reveal disparities in stakeholders' existing mental models and their perceptions of the proposed mobile health solution. We argue that fostering a common understanding of mobile health, as well as elucidating an improved understanding of processes and team behaviours, will mitigate the risk of resistance among stakeholders involved in the design and delivery of community healthcare services and culminate in a positive attitude towards new mobile health solutions among these stakeholders. We highlight the need to enhance communication and training from national to rural levels to promote complementary mental models and positively influence team performance.

Reporting preclinical anesthesia study (REPEAT): Evaluating the quality of reporting in the preclinical anesthesiology literature.

Poor reporting quality may contribute to irreproducibility of results and failed 'bench-to-bedside' translation. Consequently, guidelines have been developed to improve the complete and transparent reporting of in vivo preclinical studies. To examine the impact of such guidelines on core methodological and analytical reporting items in the preclinical anesthesiology literature, we sampled a cohort of studies. Preclinical in vivo studies published in Anesthesiology, Anesthesia & Analgesia, Anaesthesia, and the British Journal of Anaesthesia (2008-2009, 2014-2016) were identified. Data was extracted independently and in duplicate. Reporting completeness was assessed using the National Institutes of Health Principles and Guidelines for Reporting Preclinical Research. Risk ratios were used for comparative analyses. Of 7615 screened articles, 604 met our inclusion criteria and included experiments reporting on 52 490 animals. The most common topic of investigation was pain and analgesia (30%), rodents were most frequently used (77%), and studies were most commonly conducted in the United States (36%). Use of preclinical reporting guidelines was listed in 10% of applicable articles. A minority of studies fully reported on replicates (0.3%), randomization (10%), blinding (12%), sample-size estimation (3%), and inclusion/exclusion criteria (5%). Statistics were well reported (81%). Comparative analysis demonstrated few differences in reporting rigor between journals, including those that endorsed reporting guidelines. Principal items of study design were infrequently reported, with few differences between journals. Methods to improve implementation and adherence to community-based reporting guidelines may be necessary to increase transparent and consistent reporting in the preclinical anesthesiology literature.

Neural Coding of Cell Assemblies via Spike-Timing Self-Information.

Cracking brain's neural code is of general interest. In contrast to the traditional view that enormous spike variability in resting states and stimulus-triggered responses reflects noise, here, we examine the "Neural Self-Information Theory" that the interspike-interval (ISI), or the silence-duration between 2 adjoining spikes, carries self-information that is inversely proportional to its variability-probability. Specifically, higher-probability ISIs convey minimal information because they reflect the ground state, whereas lower-probability ISIs carry more information, in the form of "positive" or "negative surprisals," signifying the excitatory or inhibitory shifts from the ground state, respectively. These surprisals serve as the quanta of information to construct temporally coordinated cell-assembly ternary codes representing real-time cognitions. Accordingly, we devised a general decoding method and unbiasedly uncovered 15 cell assemblies underlying different sleep cycles, fear-memory experiences, spatial navigation, and 5-choice serial-reaction time (5CSRT) visual-discrimination behaviors. We further revealed that robust cell-assembly codes were generated by ISI surprisals constituted of ~20% of the skewed ISI gamma-distribution tails, conforming to the "Pareto Principle" that specifies, for many events-including communication-roughly 80% of the output or consequences come from 20% of the input or causes. These results demonstrate that real-time neural coding arises from the temporal assembly of neural-clique members via silence variability-based self-information codes.

Distinct retrosplenial cortex cell populations and their spike dynamics during ketamine-induced unconscious state.

Ketamine is known to induce psychotic-like symptoms, including delirium and visual hallucinations. It also causes neuronal damage and cell death in the retrosplenial cortex (RSC), an area that is thought to be a part of high visual cortical pathways and at least partially responsible for ketamine's psychotomimetic activities. However, the basic physiological properties of RSC cells as well as their response to ketamine in vivo remained largely unexplored. Here, we combine a computational method, the Inter-Spike Interval Classification Analysis (ISICA), and in vivo recordings to uncover and profile excitatory cell subtypes within layers 2&3 and 5&6 of the RSC in mice within both conscious, sleep, and ketamine-induced unconscious states. We demonstrate two distinct excitatory principal cell sub-populations, namely, high-bursting excitatory principal cells and low-bursting excitatory principal cells, within layers 2&3, and show that this classification is robust over the conscious states, namely quiet awake, and natural unconscious sleep periods. Similarly, we provide evidence of high-bursting and low-bursting excitatory principal cell sub-populations within layers 5&6 that remained distinct during quiet awake and sleep states. We further examined how these subtypes are dynamically altered by ketamine. During ketamine-induced unconscious state, these distinct excitatory principal cell subtypes in both layer 2&3 and layer 5&6 exhibited distinct dynamics. We also uncovered different dynamics of local field potential under various brain states in layer 2&3 and layer 5&6. Interestingly, ketamine administration induced high gamma oscillations in layer 2&3 of the RSC, but not layer 5&6. Our results show that excitatory principal cells within RSC layers 2&3 and 5&6 contain multiple physiologically distinct sub-populations, and they are differentially affected by ketamine.

Hospice, She Yelped: Examining the Quantity and Quality of Decision Support Available to Patient and Families Considering Hospice.

CONTEXT: Whether to engage hospice is one of the most difficult medical decisions patients and families make. Meanwhile, misperceptions about hospice persist. Within this context, the breadth and depth of patient decision support materials for hospice are unknown. OBJECTIVES: The objective of this study was to identify available patient decision aids (PtDAs) relating information about hospice care and compare that information with the informational needs expressed by real-world health care consumers. METHODS: First, the research team conducted an environmental scan of available PtDAs that included hospice as a treatment option and met six basic criteria defined by the International Patient Decision Aid Standards. Second, laypersons conducted an organic Web search for information regarding hospice, followed by a semi-structured interview eliciting perceptions of the available information. The setting was the University of Colorado Health Care System. Participants included 20 laypersons aged 18 years or older. RESULTS: The environmental scan identified 7PtDAs that included hospice. No PtDAs were designed primarily around hospice; rather, hospice was referenced under the umbrella of another treatment option. The layperson search identified information distinct from the scan; no participant accessed any of the above 7PtDAs. Many participants found the available online material confusing and biased, while failing to provide clear information on cost and lacking desired patient and caregiver testimonials. CONCLUSION: We found no formal PtDA designed primarily to help patients/families contemplating hospice. Furthermore, accessible online information about hospice does not appear to meet patient and caregiver decisional needs. These findings support the development and dissemination of high-quality decision support materials for hospice.