The aim of this policy article is twofold: (i) to provide a summary and update of recent important policy developments, in particular relevant guidance on the use of real-world data/real-world evidence (RWD/RWE) by health technology assessment (HTA) bodies and (ii) to set out our policy recommendations on how the different elements of an “RWE framework” we have previously developed could support, further enhance and facilitate the use of RWE for HTA purposes and by HTA bodies and payers.

We undertook a targeted review and analysis of recent important policy developments. The aim was to build on our recommendations from previous work on the “RWE Framework,” and consider how the relevant tools from our Framework can further enhance and facilitate the use of RWE for HTA purposes and by HTA bodies/payers.

We provide eight conditions that we argue would, in combination, constitute the optimal use and acceptance of RWD/RWE for HTA. We believe that, should the eight conditions hold, RWD/RWE would enable more efficient access to medicines and healthcare technologies for patients.

High-quality, fit-for-purpose RWD/RWE can and should be used more frequently in HTA. Multi-stakeholder and cross-geography collaborative partnerships are needed to align on best practices to optimize the evidence that needs to be generated to satisfy all stakeholders’ needs.

Emerging evidence suggests a potential association between “leaky gut syndrome” and low-grade systemic inflammation in individuals with psychiatric disorders, such as schizophrenia. Gut dysbiosis could increase intestinal permeability, allowing the passage of toxins and bacteria into the systemic circulation, subsequently triggering immune-reactive responses. This study delves into understanding the relationship between plasma markers of intestinal permeability and symptom severity in schizophrenia. Furthermore, the influence of lifestyle habits on these intestinal permeability markers was determined.

Biomarkers of intestinal permeability, namely lipopolysaccharide-binding protein (LBP), lipopolysaccharides (LPS), and intestinal fatty acid binding protein (I-FABP), were analyzed in 242 adult schizophrenia patients enrolled in an observational, cross-sectional, multicenter study from four centers in Spain (PI17/00246). Sociodemographic and clinical data were collected, including psychoactive drug use, lifestyle habits, the Positive and Negative Syndrome Scale to evaluate schizophrenia symptom severity, and the Screen for Cognitive Impairment in Psychiatry to assess cognitive performance.

Results revealed elevated levels of LBP and LPS in a significant proportion of patients with schizophrenia (62% and 25.6%, respectively). However, no statistically significant correlation was observed between these biomarkers and the overall clinical severity of psychotic symptoms or cognitive performance, once confounding variables were controlled for. Interestingly, adherence to a Mediterranean diet was negatively correlated with I-FABP levels (beta = −0.186, t = −2.325, p = 0.021), suggesting a potential positive influence on intestinal barrier function.

These findings underscore the importance of addressing dietary habits and promoting a healthy lifestyle in individuals with schizophrenia, with potential implications for both physical and psychopathological aspects of the disorder.

A retrospective naturalistic evaluation was undertaken to identify if pre- and post-disaster factors may predict the likelihood of those considered “at risk” of post-traumatic stress disorder (PTSD) entering a post-disaster clinical treatment program.

The intake data of 881 people referred to the program following the Queensland (Australia) natural disasters of 2010-11 was evaluated. Those referred scored >2 on the Primary Care PTSD scale. Assessment included the disaster exposure experience, demographic and clinical information, and measures of coping and resilience. Descriptive analyses and a Classification Tree Analysis (CTA) were undertaken to ascertain which factors may predict treatment participation.

The treatment group (TG) in comparison to the non-treatment group (NTG) were more likely to perceive their life was threatened (85.1% vs 8.1%), less able to cope (67% vs 25.8%) and less resilient (4.2% vs 87.5%). The CTA using all the assessment variables found the Connor-Davidson (2-item scale) (P < 0.001), degree of property damage (P < 0.001), financial losses (P < 0.001), perception their life was threatened (P < 0.001) and insurance claims (P < 0.003) distinguished the TG from the NTG.

The study identified factors that distinguished the TG from the NTG and predicted the likelihood of participation in a post-disaster mental health treatment.

Following the 2010-2011 floods and cyclones that affected 78% of Queensland, Australia, a State-wide mental health response was established. The response plan included a 24-hour access line. This study examines the effectiveness of the mental health screening program conducted via the State-wide health call center (13HEALTH) in 2012.

Callers to the 13HEALTH line were screened to assess the impact of the disaster. The 13HEALTH clinicians administered the Primary Care-Posttraumatic Stress Disorder Scale (PC-PTSD) screening measure. Those scoring more than two on the PC-PTSD Scale were provided information on the emotional impact of disasters and a referral to the post-disaster specialist mental health program (SMHP). For calls related to those under 18, a single-item question assessed behavioral or emotional changes since the natural disasters. Those with identified changes were offered a referral to a post-disaster SMHP.

The study evaluates the relationship between disaster exposure and the likelihood of 13HEALTH callers experiencing physical health concerns and unacknowledged mental health symptoms. The program’s cost for the 12 months of 2012 was assessed using data from the financial contract.

In 2012, there were 205,064 calls to 13HEALTH: 19,708 identified as residing in a flood or cyclone-affected area, 7,315 adults indicated they were personally affected, and 907 scored more than two on the PC-PTSD Scale. Only 700 agreed to a referral to the SMHP. There were 290 children under 18 assessed as at risk; 207 accepted a referral to a SMHP.

Regions that experienced a greater impact from the floods and cyclones were 1.3-2.3 times more likely to report being personally affected by the floods and cyclones. Similarly, these regions had more callers scoring more than two on the PC-PTSD Scale. The total cost of the 13HEALTH program for 2012 was $53,284 (AU) across all age groups.

The 13HEALTH general health post-disaster screening program demonstrates opportunistic screening may assist identification of those with unmet mental health needs. The data indicate an increased likelihood of personal exposure in the more affected regions with an increased risk of unrecognized psychological symptoms as assessed by the PC-PTSD Scale. However, more than 20% declined referral to a SMHP.

This paper reports the results of the collaboration within the European initiative of new Reimbursement and aCCess Approaches (EUreccA) which is concerned with the use of real-world evidence (RWE) in health technology assessment (HTA) decision-making. The work grew from the observation of a large, very experienced group of HTA practitioners which found that the use of RWE varied depending on the type of question asked and the particulars of the data source(s) used. We set out to examine how RWE is used in HTA decision-making and to make proposals on its facilitation.

Literature reviews covering earlier reviews of RWE use, academic papers, and HTA agency websites were combined with case studies involving interviews with decision-makers in four countries (England, France, Italy, Sweden) to identify the circumstances of breakdown of RWE use and to build a categorization of the uses of RWE and associated difficulties. This evidence supported the creation of a taxonomy of pairings of data sources and the questions they were used to address. The face validity of the approach was tested at an advisory board of senior HTA practitioners.

In total, 27 questions were identified and 10 types of data source, giving 270 pairings. These pairings were linked to relevant methods guidance and to examples of their use, itemizing HTA issues and decisions made. Reports are being prepared for publication, covering the detail of the methods of the literature searches; methods of the country case studies; a description of the taxonomy; and guidance on governance.

When using RWE in HTA decision-making, the detail of the particular data sources and question addressed matter. Recently, both the International Society for Pharmacoeconomics and Outcomes Research (ISPOR) and the Real-World Transparency Initiative have argued for a registry of the uses of RWE. The work described here offers a starting classification of the material that should be held in such a registry, and which in itself could be developed by the stakeholders, both agencies and companies, that use it, furthering trust and confidence.

Following natural disasters, rural general practitioners (GPs) are expected to undertake several roles, including identifying those experiencing psychological distress and providing evidence-informed mental health care. This paper reports on a collaborative mental health program developed to support a rural GP practice (population <1,500) and a disaster response service.

The program provided specialized disaster mental health care via the placement of a clinician in the GP facility. In collaboration with the GP practice, the program offered opportunistic screening using the Primary Care Posttraumatic Stress Disorder (PTSD) Scale (PC-PTSD) for probable PTSD as the primary measure and the Kessler 6 (K6) as a secondary measure. Those scoring higher than two on the PC-PTSD scale were referred to the mental health clinician (MHC) for further assessment and treatment.

Sixty screening assessments were completed. Fourteen patients (male = 3; female = 11) scored higher than two on the PC-PTSD. The referred group PC-PTSD mean score was 3.14 and K6 mean score of 19. Those not referred had a PC-PTSD mean score = 0.72 and K6 mean score = 7.30. The treatment and non-treatment groups differed significantly (PC-PTSD: P <.00001 and K6: P <.00001). A prior history of trauma exposure was notable in the intervention group. Eight reported a history of domestic violence, seven histories of sexual abuse, five childhood sexual abuse, and eight intimate partner violence (IPV).

A post-disaster integrated GP and mental health program in a rural community can assist in identifying individuals experiencing post-disaster psychological distress using opportunistic psychological screening. The findings indicate that collaborative mental health programs may effectively support rural communities post-disaster.

An increasing number of innovative therapies (e.g., gene- and cell-based treatments) have been developed in the past 20 years. Despite the significant clinical potential of these therapies, access delays may arise because of differing perspectives of manufacturers and payers regarding issues such as the value of the product, clinical and financial uncertainties, and sustainability.

Managed entry agreements (MEAs) can enable access to treatments that would not be reimbursed by conventional methods because of such concerns. However, although MEA typologies exist, there is currently no structured process to come to agreements on MEAs, which can be difficult to decide upon and implement.

To facilitate more structured MEA negotiations, we propose a conceptual “value-based negotiation framework” with corresponding application tools.

The framework was developed based on an iterative process of scientific literature review and expert input.

The framework aims to (i) systematically identify and prioritize manufacturer and payer concerns about a new treatment, and (ii) select a mutually acceptable combination of MEA terms that can best address priority concerns, with the lowest possible implementation burden.

The proposed framework will be tested in practice, and is a step toward supporting payers and manufacturers to engage in more structured, transparent negotiations to balance the needs of both sides, and enabling quicker, more transparent MEA negotiations and patient access to innovative products.

Lack of knowledge and discriminatory attitudes and behaviours towards individuals with mental disorders is a worldwide problem but may be particularly damaging for young people. This pilot study examined knowledge, attitudes and behaviours towards schizophrenia, bipolar disorder and autism within a large sample of adults in Ireland, a country with the youngest population in Europe, in order to better understand public views on these groups.

In a correlational, cross-sectional design, 307 adults in Ireland over the age of 18 completed a questionnaire over Google Forms examining knowledge, attitudes and behaviours towards schizophrenia, bipolar disorder and autism. Responses to questions specifically relating to each diagnosis were compared using trimmed mean ANOVA to examine whether responses to questions differed depending on diagnosis.

Results indicate varied knowledge, attitudes and behaviours towards these groups, but a majority believe it should be a research priority. ANOVA and post hoc tests revealed significant differences in knowledge, attitudes and behaviours towards each of schizophrenia, bipolar disorder, and autism (p < 0.005), and reported attitudes and behaviours towards schizophrenia were more negative than either bipolar disorder or autism. A majority of participants (54.8%) felt not informed enough about mental health by the media.

In our Irish sample, type and level of stigma varies according to mental health diagnosis. Our sample also report feeling inadequately informed about mental health by the media. Thus future policy and campaigns could consider targeting individual mental health diagnoses, with a focus on increasing familiarity and knowledge.

Many mental disorders, including depression, bipolar disorder and schizophrenia, are associated with poor dietary quality and nutrient intake. There is, however, a deficit of research looking at the relationship between obsessive–compulsive disorder (OCD) severity, nutrient intake and dietary quality.

This study aims to explore the relationship between OCD severity, nutrient intake and dietary quality.

A post hoc regression analysis was conducted with data combined from two separate clinical trials that included 85 adults with diagnosed OCD, using the Structured Clinical Interview for DSM-5. Nutrient intakes were calculated from the Dietary Questionnaire for Epidemiological Studies version 3.2, and dietary quality was scored with the Healthy Eating Index for Australian Adults – 2013.

Nutrient intake in the sample largely aligned with Australian dietary guidelines. Linear regression models adjusted for gender, age and total energy intake showed no significant associations between OCD severity, nutrient intake and dietary quality (all P > 0.05). However, OCD severity was inversely associated with caffeine (β = −15.50, 95% CI −28.88 to −2.11, P = 0.024) and magnesium (β = −6.63, 95% CI −12.72 to −0.53, P = 0.034) intake after adjusting for OCD treatment resistance.

This study showed OCD severity had little effect on nutrient intake and dietary quality. Dietary quality scores were higher than prior studies with healthy samples, but limitations must be noted regarding comparability. Future studies employing larger sample sizes, control groups and more accurate dietary intake measures will further elucidate the relationship between nutrient intake and dietary quality in patients with OCD.

Retrospective self-report is typically used for diagnosing previous pediatric traumatic brain injury (TBI). A new semi-structured interview instrument (New Mexico Assessment of Pediatric TBI; NewMAP TBI) investigated test–retest reliability for TBI characteristics in both the TBI that qualified for study inclusion and for lifetime history of TBI.

One-hundred and eight-four mTBI (aged 8–18), 156 matched healthy controls (HC), and their parents completed the NewMAP TBI within 11 days (subacute; SA) and 4 months (early chronic; EC) of injury, with a subset returning at 1 year (late chronic; LC).

The test–retest reliability of common TBI characteristics [loss of consciousness (LOC), post-traumatic amnesia (PTA), retrograde amnesia, confusion/disorientation] and post-concussion symptoms (PCS) were examined across study visits. Aside from PTA, binary reporting (present/absent) for all TBI characteristics exhibited acceptable (≥0.60) test–retest reliability for both Qualifying and Remote TBIs across all three visits. In contrast, reliability for continuous data (exact duration) was generally unacceptable, with LOC and PCS meeting acceptable criteria at only half of the assessments. Transforming continuous self-report ratings into discrete categories based on injury severity resulted in acceptable reliability. Reliability was not strongly affected by the parent completing the NewMAP TBI.

Categorical reporting of TBI characteristics in children and adolescents can aid clinicians in retrospectively obtaining reliable estimates of TBI severity up to a year post-injury. However, test–retest reliability is strongly impacted by the initial data distribution, selected statistical methods, and potentially by patient difficulty in distinguishing among conceptually similar medical concepts (i.e., PTA vs. confusion).

Obsessive–compulsive disorder (OCD) is often challenging to treat and resistant to psychological interventions and prescribed medications. The adjunctive use of nutraceuticals with potential neuromodulatory effects on underpinning pathways such as the glutamatergic and serotonergic systems is one novel approach.

To assess the effectiveness and safety of a purpose-formulated combination of nutraceuticals in treating OCD: N-acetyl cysteine, L-theanine, zinc, magnesium, pyridoxal-5′ phosphate, and selenium.

A 20-week open label proof-of-concept study was undertaken involving 28 participants with treatment-resistant DSM-5-diagnosed OCD, during 2017 to 2020. The primary outcome measure was the Yale-Brown Obsessive–Compulsive Scale (YBOCS), administered every 4 weeks.

An intention-to-treat analysis revealed an estimated mean reduction across time (baseline to week-20) on the YBOCS total score of −7.13 (95% confidence interval = −9.24, −5.01), with a mean reduction of −1.21 points per post-baseline visit (P ≤ .001). At 20-weeks, 23% of the participants were considered “responders” (YBOCS ≥35% reduction and “very much” or “much improved” on the Clinical Global Impression-Improvement scale). Statistically significant improvements were also revealed on all secondary outcomes (eg, mood, anxiety, and quality of life). Notably, treatment response on OCD outcome scales (eg, YBOCS) was greatest in those with lower baseline symptom levels, while response was limited in those with relatively more severe OCD.

While this pilot study lacks placebo-control, the significant time effect in this treatment-resistant OCD population is encouraging and suggests potential utility especially for those with lower symptom levels. Our findings need to be confirmed or refuted via a follow-up placebo-controlled study.

This scoping review aims to map the roles of rural and remote primary health care professionals (PHCPs) during disasters.

Disasters can have catastrophic impacts on society and are broadly classified into natural events, man-made incidents, or a mixture of both. The PHCPs working in rural and remote communities face additional challenges when dealing with disasters and have significant roles during the Prevention, Preparedness, Response, and Recovery (PPRR) stages of disaster management.

A Johanna Briggs Institute (JBI) scoping review methodology was utilized, and the search was conducted over seven electronic databases according to a priori protocol.

Forty-one papers were included and sixty-one roles were identified across the four stages of disaster management. The majority of disasters described within the literature were natural events and pandemics. Before a disaster occurs, PHCPs can build individual resilience through education. As recognized and respected leaders within their community, PHCPs are invaluable in assisting with disaster preparedness through being involved in organizations’ planning policies and contributing to natural disaster and pandemic surveillance. Key roles during the response stage include accommodating patient surge, triage, maintaining the health of the remaining population, instituting infection control, and ensuring a team-based approach to mental health care during the disaster. In the aftermath and recovery stage, rural and remote PHCPs provide long-term follow up, assisting patients in accessing post-disaster support including delivery of mental health care.

Rural and remote PHCPs play significant roles within their community throughout the continuum of disaster management. As a consequence of their flexible scope of practice, PHCPs are well-placed to be involved during all stages of disaster, from building of community resilience and contributing to early alert of pandemics, to participating in the direct response when a disaster occurs and leading the way to recovery.