EUPATI Guidance for Patient Involvement in Medicines Research and Development (R&D); Guidance for Pharmaceutical Industry-Led Medicines R&D

The importance and merits of greater patient involvement in medicines research and development (R&D) are commonly acknowledged and are thought to offer benefits for all involved parties. It helps to improve discovery, development, and evaluation of new effective medicines, based on the collaborative identification and understanding of unmet needs, research priorities, optimization of clinical study design, outcome measures, and endpoint development. It can result in increased transparency, trust and mutual respect between patients and other stakeholders. This applies to all stages of medicines R&D, from industry-led research, to regulation and licensing of medicines, to appraisal by health technology assessment (HTA) bodies. Integration of patients into the medicines development process needs to be structured and governed by clear rules and modes of operation to be effective and yield the best results for all stakeholders. Existing codes of practice for patient involvement with various stakeholders do not comprehensively cover the full scope of R&D, with the exception of more general statements applicable to interaction. Overarching guidance on meaningful and ethical interaction is missing. One specific aim of the European Patients' Academy on Therapeutic Innovation (EUPATI) was to close this gap through the development of guidance documents for selected stakeholders. Four separate guidance documents were developed, incorporating the results from comprehensive internal and external consultation. They cover patient involvement in: pharmaceutical industry-led medicines R&D; ethics committees; regulatory authorities; HTA. Each guidance suggests where patient involvement could be adopted or strengthened. The EUPATI guidance document for patient involvement in industry-led medicines research and development covers the interaction between patients and the pharmaceutical industry within all functions throughout the medicines R&D lifecycle in relation to medicines for human use. It relates to activities pre-approval and post approval, involving individuals and groups of patients. The guideline distinguishes between the level of expertise in a disease area that is required and the different areas where patient involvement can take place; however, this is not meant to limit involvement, and these opportunities may change and increase over time. This EUPATI guidance document is aimed at the pharmaceutical industry who want to engage patients in R&D activities, however all stakeholders involving patients in pharmaceutical-led medicines R&D should understand and use this EUPATI guidance document

EUPATI Guidance for Patient Involvement in Medicines Research and Development: Health Technology Assessment

The main aim of health technology assessment (HTA) is to inform decision making by health care policy makers. It is a systematic process that evaluates the use of health technologies and generally involves a critical review of international evidence related to clinical effectiveness of the health technology vs. the best standard of care. It can also include an evaluation of cost effectiveness, and social and ethical impacts in the local health care system. The HTA process advises whether or not a health technology should be used, and if so, how it is best used and which patients are most likely to benefit from it. The importance of patient involvement in HTA is becoming widely recognized, for scientific and democratic reasons. The extent of patient involvement in HTA varies considerably across Europe. Commonly HTA is still focused on quantitative evidence to determine clinical and/or cost effectiveness, but the interest in understanding patients' experiences and preferences is increasing. Some HTA bodies provide support for participation in their processes, but again this varies widely across Europe. The involvement of patients in HTA is determined at the national and regional level, and is not subject to any European-wide legislation. The guidance text presented in this article was developed as part of the work of the European Patients' Academy on Therapeutic Innovation (EUPATI) and covers the interaction between HTA bodies and patients and their representatives when medicines are being assessed. Other EUPATI guidance documents relate to patient involvement in pharmaceutical industry-led research and development, ethics committees, and regulatory authorities. The guidance provides recommendations for activities to support patient involvement in HTA bodies and specific guidance for individual HTA processes. It seeks to improve patient involvement, using the outcomes of published research and consensus-building exercises. It also draws on good practice examples from individual HTA bodies. The guidance is not intended to be prescriptive and should be used according to specific circumstances, national legislation, or the unique needs of each interaction. This article represents the formal publication of the HTA guidance text with discussion about recent progress in, and continuing barriers to, patient involvement in HTA

EUPATI and Patients in Medicines Research and Development: Guidance for Patient Involvement in Ethical Review of Clinical Trials

Involvement of patients in the research and development process (R&D) of new medicines—in all areas of indications—today is a widely accepted strategy in pharmaceutical industry to ensure relevance and suitability of the treatment under development. This may consist in, but is not limited to, patient input to achieve more patient-friendly protocol design, endpoint, and comparator selection as well as disease-adapted study conditions in a pre- or post-marketing clinical trial. Ethical aspects and especially the balance of benefit and risk in a clinical trial are frequently judged differently by clinical researchers, regulators, ethics committees, and patients due to their different focus. The final assessment of the ethical aspects of a planned clinical trial is provided by an independent ethics committee consisting of physicians and other experts in healthcare and clinical trial methodology as well as of lay persons. The participation of patients in ethics committees is a much-discussed concept, its suitability disputed in many countries, and only limited experience on best practices is available. In order to be effective and yield the best results for all stakeholders, integration of patients into the medicines development process needs to be structured and governed by clear, mutually agreed rules and modes of operation. Communication and collaboration processes need to be systematically implemented to establish transparency, trust and respect between those developing new medicines and their users, respectively between those involved in design and approval of clinical trials and participants. In particular agreement on the ethical aspects of a clinical trial and/or its overall ethical acceptability is a prerequisite before the start of a clinical trial. Existing codes of practice for patient involvement with various stakeholders do not comprehensively cover the full scope of R&D, with the exception of more general statements on interaction. Overarching guidance on meaningful and ethical interaction is missing. One specific aim of the European Patients' Academy on Therapeutic Innovation (EUPATI) was to close this gap through the development of guidance documents for ethics committees, pharmaceutical industry-led medicines R&D, regulatory authorities, and health technology assessment (HTA). This EUPATI “Guidance for patient involvement in ethical review of clinical trials” gives practical recommendations for ground rules and lists options for conditions and practices for involving patients in the work of ethics committees to enable trustful and constructive collaboration whatever the national (legal) framework for patient involvement in ethics committees might be. The guidance sets the collaboration of patients in ethics committees in the broader context of relevance and opportunities for patient input on ethics in the overall medicines R&D and specifically the overall clinical trial process from concept development to trial result reporting in lay summaries. In addition to a presentation of the full text of the Guidance, this article aims at providing additional background information on the development process of the Guidance, as well as insight into the current debate on this topic

Impact of integrase inhibitors on cardiovascular disease events in people with HIV starting antiretroviral therapy.

BACKGROUND Integrase strand transfer inhibitors (INSTI) have been associated with an increased risk for cardiovascular disease (CVD) events. We investigated the impact of starting INSTI-based antiretroviral therapy (ART) on CVD events among treatment-naïve people with HIV (PWH) using a target trial framework, which reduces the potential for confounding and selection bias. METHODS We included Swiss HIV Cohort Study participants who were ART-naïve after 05/2008, when INSTI became available in Switzerland. Individuals were categorized according to their first ART regimen (INSTI vs. other ART) and were followed from ART start until the first of CVD event (myocardial infarction, stroke, or invasive cardiovascular procedure), loss to follow-up, death, or last cohort visit. We calculated hazard ratios and risk differences using pooled logistic regression models with inverse probability of treatment and censoring weights. RESULTS Of 5362 participants (median age 38 years, 21% women, 15% of African origin), 1837 (34.3%) started INSTI-based ART, and 3525 (65.7%) started other ART. Within 4.9 years (IQR 2.4-7.4), 116 CVD events occurred. Starting INSTI-based ART was not associated with an increase in CVD events (adjusted hazard ratio 0.80, 95% confidence interval [CI] 0.46-1.39). Adjusted risk differences between individuals who started INSTI and those who started other ART were -0.17% (95% CI -0.37-0.19) after one year, -0.61% (-1.54-0.22) after 5 years, and -0.71% (-2.16-0.94) after 8 years. CONCLUSIONS In this target trial emulation, we found no difference in short or longer term risk for CVD events between treatment-naïve PWH who started INSTI-based and those on other ART

Long-term trends in hepatitis C prevalence, treatment uptake and liver-related events in the Swiss HIV Cohort Study.

BACKGROUND AND AIMS Treatment for chronic hepatitis C virus (HCV) infections changed dramatically in the last decade. We assessed changes in the prevalence of replicating HCV infection, treatment uptake and liver-related morbidity and mortality in persons with HIV (PWH) and hepatitis C in the Swiss HIV cohort study. METHODS We included all cohort participants between 2002 and 2021. We assessed yearly prevalence of replicating HCV infection, overall and liver-related mortality, as well as the yearly incidence of liver-related events in persons with at least one documented positive HCV-RNA. RESULTS Of 14 652 participants under follow-up, 2294 had at least one positive HCV-RNA measurement. Of those, 1316 (57%) ever received an HCV treatment. Treatment uptake increased from 8.1% in 2002 to a maximum of 32.6% in 2016. Overall, prevalence of replicating HCV infection declined from 16.5% in 2004 to 1.3% in 2021. HCV prevalence declined from 63.2% to 7.1% in persons who inject drugs, and from 4.1% to 0.6% in men who have sex with men. Among the 2294 persons with replicating HCV infection, overall mortality declined from a maximum of 3.3 per 100 patient-years (PY) to 1.1 per 100 PY, and incidence of liver-related events decreased from 1.4/100 PY to 0.2/100 PY. CONCLUSIONS The introduction of DAA therapy was associated with a more than 10-fold reduction in prevalence of replicating HCV infection in PWH, approaching the estimates in the general population. Overall mortality and liver-related events declined substantially in persons living with HIV and hepatitis C

Triggers of change in sexual behavior among people with HIV: The Swiss U = U statement and Covid-19 compared.

We assessed changes in sexual behaviour among people with HIV (PWH) over 20 years. Condom use with stable partners steadily declined from over 90% to 29% since the Swiss U = U statement with similar trajectories between men who have sex with men (MSM) and heterosexuals. Occasional partnership remained higher among MSM compared to heterosexuals even during COVID-19 social distancing

Long-term trends in hepatitis C prevalence, treatment uptake and liver-related events in the Swiss HIV Cohort Study

BACKGROUND AND AIMS: Treatment for chronic hepatitis C virus (HCV) infections changed dramatically in the last decade. We assessed changes in the prevalence of replicating HCV infection, treatment uptake and liver-related morbidity and mortality in persons with HIV (PWH) and hepatitis C in the Swiss HIV cohort study. METHODS: We included all cohort participants between 2002 and 2021. We assessed yearly prevalence of replicating HCV infection, overall and liver-related mortality, as well as the yearly incidence of liver-related events in persons with at least one documented positive HCV-RNA. RESULTS: Of 14 652 participants under follow-up, 2294 had at least one positive HCV-RNA measurement. Of those, 1316 (57%) ever received an HCV treatment. Treatment uptake increased from 8.1% in 2002 to a maximum of 32.6% in 2016. Overall, prevalence of replicating HCV infection declined from 16.5% in 2004 to 1.3% in 2021. HCV prevalence declined from 63.2% to 7.1% in persons who inject drugs, and from 4.1% to 0.6% in men who have sex with men. Among the 2294 persons with replicating HCV infection, overall mortality declined from a maximum of 3.3 per 100 patient-years (PY) to 1.1 per 100 PY, and incidence of liver-related events decreased from 1.4/100 PY to 0.2/100 PY. CONCLUSIONS: The introduction of DAA therapy was associated with a more than 10-fold reduction in prevalence of replicating HCV infection in PWH, approaching the estimates in the general population. Overall mortality and liver-related events declined substantially in persons living with HIV and hepatitis C

Risk Factors and Incidence of Sexually Transmitted Infections in the Swiss HIV Cohort Study

BACKGROUND: Sexually transmitted infections (STIs) are common among people with human immunodeficiency virus (PWH), but there are limited data about risk factors and incidence of STIs in large, representative cohort studies. METHODS: We assessed incidence and risk factors of STIs reported by treating physicians within the Swiss HIV Cohort Study (SHCS). Sexually transmitted infections and demographic, clinical, and behavioral characteristics were prospectively collected at 6-month follow-up visits between October 2017 and November 2019. We used multilevel Poisson regression to assess incidence rate ratios of different STIs. RESULTS: Among 10 140 study participants, a total of 1634 STIs in 1029 SHCS participants were reported over 17 766 person-years of follow up (PYFUP). The overall incidence of any reported STI was 91.9 per 1000 PYFU (95% confidence interval [CI], 85.8 –98.5). Among the 1634 STI episodes, there were 573 (35.1%) incident cases of syphilis, 497 gonorrhea (30.4%), and 418 chlamydia (25.6%). Men who have sex with men (MSM) younger than 50 years represented 21% of the study population, but accounted for 61% of reported STIs. Male sex (adjusted incidence rate ratio [aIRR], 2.03; 95% CI, 1.36–3.02), MSM (aIRR, 3.62; 95% CI, 2.88–4.55), age group 18–34 years (aIRR, 1.78; 95% CI, 1.51–2.10), history of sexual relationships with occasional partners (aIRR, 6.87; 95% CI, 5.40–8.73), and reporting injecting drug use (aIRR, 2.48; 95% CI, 1.91–3.23) were associated with a higher risk of incident STIs. CONCLUSIONS: Sexually transmitted infections were frequent among PWH and varied considerably between age and risk groups. Screening programs and recommendations for STI testing need to be adapted according to risk factors and demographic characteristics

Triggers of change in sexual behavior among people with HIV: The Swiss U = U statement and Covid-19 compared

We assessed changes in sexual behaviour among people with HIV (PWH) over 20 years. Condom use with stable partners steadily declined from over 90% to 29% since the Swiss U = U statement with similar trajectories between men who have sex with men (MSM) and heterosexuals. Occasional partnership remained higher among MSM compared to heterosexuals even during COVID-19 social distancing

Sexual Behaviour and STI Incidence in Sexually Active MSM Living With HIV in Times of COVID-19.

Despite decreased numbers of sexual partners, the COVID-19 pandemic had limited impact on the prevalence of attending private sex parties, traveling for sex within Switzerland, and practicing chemsex in men with HIV who have sex with men. COVID-19 risk perception was low, and STI-diagnosis incidence rates remained stable over time