Building on the successes of patient-focused drug development: a call for new policies to maintain momentum.

Since its commencement as part of the Food and Drug Administration's (FDA) Prescription Drug User Fee Act (PDUFA) V in 2012, patient-focused drug development (PFDD) has become an integral part of the drug development paradigm. FDA encourages the development and use of Patient-Experience Data (PED) as it provides important information on the patients' needs and perspectives and inform regulatory decision-making. While the FDA is required to fill out a table which includes a list of various types of Patient Experience Data (PED) and if such data was reviewed by FDA as part of a drug application, there is still a need to understand how FDA uses PED in its regulatory decision-making. This article examines whether new policies are needed to ensure the full potential of PFDD.

Erratum: Assessing the credibility of a drug's effects: identification and judgment of uncertainty by the Dutch Medicines Evaluation Board.

[This corrects the article DOI: 10.3389/fmed.2024.1409259.].

Stakeholders' Perspectives on Current Issues in Data Monitoring Committees.

Data Monitoring Committees (DMCs) are groups of experts that review accumulating data from one or more ongoing clinical studies and advise the Sponsor regarding the continuing safety of study subjects along with the continuing validity and scientific merit of the study. Although DMCs are widely used, considerable variability exists in their conduct. This paper offers recommendations, derived from sessions given at the 2023 Central European Network International Biometric and Statisticians in the Pharmaceutical Industry Conferences' and the authors' experiences. We focus on four topics that are part of the DMC process and where there is unclarity and inconsistency in current practices: (1) Communication with the DMC-We reflect on the importance of effective, proper communication channels between the DMC and relevant stakeholders to foster collaboration and exchange of critical information while retaining study integrity throughout. (2) Open sessions-We discuss the benefits of incorporating open sessions in DMC meetings to enhance transparency, inclusivity, and the consideration of diverse perspectives, as well as pitfalls of open sessions. (3) Access to efficacy data-We highlight the need for appropriate access to efficacy data by DMCs and discuss how to implement this in practice and how to address potential concerns regarding multiplicity. (4) Interactive data displays-We outline the utilization of interactive data displays to facilitate a more intuitive understanding of study results by the DMC. By addressing these topics, we aim to provide comprehensive practical recommendations that bridge the gap between current practices and optimal DMC functionality.

Relevance, Risks, and Benefits of Early-Phases Clinical Trials Participations for Patients With Hematological Malignancies From 2008 to 2023.

BACKGROUND: Early-phases clinical trials (Phases 1 and 2) have evolved from a traditional assessment of toxicity to an adaptive approach based on patients' medical needs and access to effective new therapies. The global risks, benefits, and relevance of early-phases clinical trials participation for patients with hematological malignancies remain poorly evaluated. PATIENTS AND METHODS: All early-phases clinical trials participations for patients with hematological malignancies, from 2008 to 2023, in a tertiary academic center in Europe, were reviewed. Patient's demographics, tumor type categories, therapeutic responses, mortality, overall survival (OS), and investigational product (IP) were assessed. RESULTS: Over the period 2008-2023, 736 patients participating in 92 different early-phases clinical trials, were analyzed. The most common tumor categories were diffuse large B-cell lymphoma (n = 253; 34.4%), acute myeloid leukemia/myelodysplastic syndrome (n = 164; 22.3%) and multiple myeloma (n = 100; 13.6%). The median OS was 14.8 (95% CI: 12.4-17.9) months and response rate 31.9%, including complete responses in 13.5% of patients. By tumor categories, the highest and lowest median duration of OS were observed for patients with Hodgkin lymphoma (99.8; [95% CI: 47.0-not reached] months) and peripheral T-cell lymphoma (8.9 [95% CI: 5.3-12.0] months), respectively. The on-protocol and treatment-related mortality rates were 5.43% and 0.54%, respectively. Overall response rate was 29.1% including 13.5% of complete response. Overall, 202 (27.5%) patients received an IP later approved by the health authorities, and those patients had better OS (18.2 months vs. 12.1 months HR: 1.160 [95% CI; 0.6977-1.391], p = 0.0283). CONCLUSION: In conclusion, patients with hematologic malignancies who have participated in early-phases clinical trials over the past 15 years have achieved variable therapeutic response rates, acceptable risk/benefit ratio and potentially significant therapeutic advantages. This study provides framework material for hematologists to further discuss clinical trial participation with their patients.

Selecting appropriate excipients for paediatric dosage form - Paediatric excipients risk assessment (PERA) framework - Part 1.

Excipients are often the major component of the formulation that critically affect the dosage form, manufacturing process, product performance, stability and safety. They exert different roles and functions in a dosage form. Selecting excipients with appropriate safety and tolerability is a major hurdle in paediatric formulation development. The suitability of a particular excipient will be dependent on the context of its use with regard to the paediatric age range, acute versus chronic use, and clinical risk-benefit of the disease, active and excipient. Scientists are encouraged to apply the principle of risk-benefit to assess the suitability of excipients to the specific paediatric population. Indicative list of parameters that should be taken into consideration and hierarchy of information sources when assessing the excipients risks is provided by regulatory agencies. However, the approach to be taken and details of how the risk evaluation should be undertaken are lacking. There is a need for a systematic approach to selection of excipients and assessment of the risk of excipient exposure. The Paediatric Excipients Risk Assessment (PERA) framework developed and proposed in this paper provides a structured, systematic decision-making framework via customizable tools and processes that can help to improve the transparency and communications on the selection and justification of use of excipients in a paediatric formulation.

A Brighton Collaboration standardized template with key considerations for a benefit-risk assessment for the Comirnaty COVID-19 mRNA vaccine.

The Brighton Collaboration Benefit-Risk Assessment of VAccines by TechnolOgy (BRAVATO) Working Group evaluates the safety and other key features of new platform technology vaccines, including nucleic acid (RNA and DNA) vaccines. This manuscript uses the BRAVATO template to report the key considerations for a benefit-risk assessment of the coronavirus disease 2019 (COVID-19) mRNA-based vaccine BNT162b2 (Comirnaty®, or Pfizer-BioNTech COVID-19 vaccine) including the subsequent Original/Omicron BA.1, Original/Omicron BA.4-5 and Omicron XBB.1.5 variant-adapted vaccines developed by BioNTech and Pfizer to protect against COVID-19 caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Initial Emergency Use Authorizations or conditional Marketing Authorizations for the original BNT162b2 vaccine were granted based upon a favorable benefit-risk assessment taking into account clinical safety, immunogenicity, and efficacy data, which was subsequently reconfirmed for younger age groups, and by real world evidence data. In addition, the favorable benefit-risk assessment was maintained for the bivalent vaccines, developed against newly arising SARS-CoV-2 variants, with accumulating clinical trial data.

Assessing the credibility of a drug's effects: identification and judgment of uncertainty by the Dutch Medicines Evaluation Board.

Medicine regulators need to judge whether a drug's favorable effects outweigh its unfavorable effects based on a dossier submitted by an applicant, such as a pharmaceutical company. Because scientific knowledge is inherently uncertain, regulators also need to judge the credibility of these effects by identifying and evaluating uncertainties. We performed an ethnographic study of assessment procedures at the Dutch Medicines Evaluation Board (MEB) and describe how regulators evaluate the credibility of an applicant's claims about the benefits and risks of a drug in practice. Our analysis shows that regulators use an investigative approach, which illustrates the effort required to identify uncertainties. Moreover, we show that regulators' expectations about the presentation, the design, and the results of studies can shape how they perceive a medicine's dossier. We highlight the importance of regulatory experience and expertise in the identification and evaluation of uncertainties. In light of our observations, we provide two recommendations to reduce avoidable uncertainty: less reliance on evidence generated by the applicant; and better communication about, and enforcement of, regulatory frameworks toward drug developers.

[Targeted therapies and immunotherapy: Positioning in the field of innovation and challenges for the therapeutic decision-making process]. / Thérapies ciblées et immunothérapie : positionnement dans le champ de l'innovation et enjeux pour le processus de décision thérapeutique.

The better understanding of the molecular, cellular, and immunological mechanisms of cancer has led to the development of targeted therapies, then immunotherapy, which have changed the approach to cancer treatment. While these treatments differ from chemotherapy in their mechanisms of action, they also allow for increased personalization of cancer care through the development of technologies that target patients more precisely. However, they are associated with several challenges: the management of uncertainty associated with their risk-benefit balance due to the lack of long-term data and sometimes scientific evidence on their effects; the complexity of integrating molecular and immunological data into the therapeutic decision; the challenge of inequalities in access to these treatments often considered revolutionary due to the required molecular characterization and/or inclusion criteria for early-phase trials; and the challenge of their appropriation and adoption by physicians and patients. This narrative review explores each of these challenges in the context of shared decision-making, the promotion of which is a guarantee of quality and safety of care for cancer patients.

The life cycle of vaccines evaluated by the European Medicines Agency.

BACKGROUND: vaccines are complex products used in healthy populations. They should be carefully regulated, and benefits should clearly outweigh risks. OBJECTIVES: To describe the evidence used to support benefit-risk evaluations of vaccines centrally assessed by the European Medicines Agency (EMA), and to identify if real-world data (RWD) was used throughout the vaccine life cycle. METHODS: Cohort study of vaccines approved in the European Union. Inclusion criteria comprised having ATC code J07 and being centrally approved between 2012 and 2022. We collected data from regulatory documents, study protocols, and, when necessary, from scientific publications. Vaccines were followed from initial approval up to March 2023. RESULTS: We included 31 vaccines addressing 17 therapeutic areas. More than 390 studies were used in the process of initial marketing authorisation (MA) and monitoring, and 174 studies were listed in initial risk management plans. We also identified 93 studies in the EU PAS register. At MA, all vaccines had at least one pivotal trial and 27 vaccines had at least one supportive study. Most pivotal trials were randomized, double-blinded and active-controlled, with immunogenicity endpoints as primary outcome. RWD was used for extension of indications and monitoring of at least 4 vaccines, and the undertaking of RWE studies was foreseen in the RMP of at least 17 vaccines. DISCUSSION: Our study revealed an important reliance on randomized controlled trials with individual-level randomization, and a significant focus on immunogenicity endpoints. The use of RWD in vaccine assessments so far has been restricted to COVID-19, and despite its challenges and limitations, we believe that efforts to expand adoption of RWE in continuous benefit-risk assessments should be made. We further highlight the need to enhance data transparency and reporting standards since heterogeneity among regulatory documents made it difficult to identify all the studies considered in vaccine evaluations.

Benefit-Risk Trade-offs and Patient Preferences for Therapy Selection in Ulcerative Colitis: a Multicountry Preference Study.

BACKGROUND: To help navigate the complex treatment landscape of ulcerative colitis (UC), we quantified the benefit-risk trade-offs that patients were willing to make when choosing treatment. METHODS: Patients completed an online discrete choice experiment. Eligible patients had a UC diagnosis for ≥6 months, were aged ≥18 years, and resided in France, Germany, Italy, Spain, or the UK. Patients chose between 2 hypothetical treatments set up to ensure trade-offs were made. Clinical trial data, literature review, and patient interviews identified treatment attributes. Relative attribute importance (RAI) scores and maximum acceptable risks were generated. A patient-centric benefit-risk assessment of 200 mg of filgotinib was conducted as an example to show how measured trade-offs can be used. RESULTS: Overall, 631 patients participated; patients had a mean age of 42.2 years and were predominantly male (75.3%). Achieving and maintaining clinical remission was the most important factor for patients (RAI 32.4%); to achieve this, patients were willing to accept slightly higher risks of blood clots, serious infections, and malignancies compared with lower risk treatment profiles. Patients also valued the convenience of oral treatments, avoiding steroids, and the ability to attend school/work. The patient-centric benefit-risk assessment suggested patients are significantly more likely to prefer Janus kinase 1 preferential inhibitor filgotinib over placebo. CONCLUSIONS: Achieving clinical remission was the highest treatment priority for patients. To attain this, patients were willing to accept some slightly higher risk treatment profiles. Patient choices in the benefit-risk assessment suggested patients were significantly more likely to prefer filgotinib over placebo.

Patients were willing to accept slightly higher risk treatment profiles over lower risk treatment profiles for an increased chance of achieving and maintaining remission. A patient-centric benefit-risk assessment suggested 200 mg of filgotinib had an acceptable benefit-risk profile.

Analyzing the 7C psychological antecedents of vaccine acceptance throughout the COVID-19 pandemic among healthcare sector workers in France: A repeated cross-sectional study (CappVac-Cov).

BACKGROUND: Across various stages of the COVID-19 pandemic and related vaccine recommendations in France, we assessed the association of the 7C-psychological antecedents with vaccine uptake/intention for booster vaccination among healthcare-sector workers (HCSWs). We also assessed whether 7C-antecedent profiles changed over time. METHODOLOGY: The Research Group for the Prevention of Occupational Infections in Healthcare Workers (GERES) conducted three repeated web-surveys which were disseminated by email chain-referral among HCSWs throughout France. The questionnaires waves took place: July-November 2021, February-March 2022 and January-March 2023 (P2, P3 and P4). We also reanalysed data from a prior similar study conducted late 2020-early 2021 (Moirangthem et al. (2022)) (P1). To evaluate the association of 7C-items with vaccine uptake-intention for future vaccination, we estimated adjusted prevalence ratios (aPR) using robust variance Poisson regression. We report the 7C-item population attributable loss in vaccine intention. RESULTS: The four surveys (P1-P4) encompassed 5234, 339, 351 and 437 participants. At earlier stages of the vaccine campaign, the principal antecedents of vaccine intention were favorable perception of vaccination benefit-risk-balance (BRB) (vs. unfavorable, aPR: 2.32), reactance to employer encouragement for vaccination (motivates vs. dissuades-me, aPR:2.23), vaccine confidence (vs. not-being-confident, aPR: 1.71) and social conformism towards vaccination (favorable vs. skeptical opinion in private environment, aPR: 1.33). Under a vaccine mandate for HCSWs, only perceiving vaccination as a collective action was associated with current vaccine status (agree vs. disagree, aPR: 2.19). At later stages of the epidemic, hypothetical booster vaccine intentions were strongly associated with BRB perception (favorable vs. unfavorable, aPR: 2.07) and perceiving vaccination as a collective action (agree vs. disagree, aPR: 1.69). Fearing a severe side effect from vaccination decreased population vaccine intention by 26.2 %. CONCLUSION: Our results suggest that both 7C-antecedents and their association with vaccine behaviour can change over time, and underscore the importance of assuring confidence in vaccine safety.

Clinical Implications of Co-administering Apixaban with Key Interacting Medications.

With many available data sources, clinicians need to consider the benefit-risk profile of individual anticoagulants when balancing the need for anticoagulation, including evaluating the risks in patients with comorbidities and potential drug-drug interactions. This narrative review presents clinical data across multiple phases of drug development for the use of apixaban, a selective factor Xa inhibitor, when taken concomitantly with other agents, and evaluates the benefit-risk profile of apixaban with these interacting medications. Key subgroup analyses from the phase 3 ARISTOTLE trial (NCT00412984) are presented using data from patients who received either concomitant inhibitors or inducers of cytochrome P450 3A4 and/or P­glycoprotein. We also review the available evidence for the use of apixaban in patients with cancer-associated thromboembolism, as well as the use of apixaban in patients with COVID-19.

[Benefit-risk assessment of three oral Chinese patent medicines for activating blood and eliminating mass in treating primary liver cancer based on network Meta-analysis and multi-criteria decision analysis].

Network Meta-analysis and multi-criteria decision analysis(MCDA) model were performed to evaluate the benefit-risk of Compound Cantharis Capsules, Huisheng Oral Solution, and Jinlong Capsules in the adjuvant treatment of primary liver cancer(PLC). The randomized controlled trial(RCT) of Compound Cantharis Capsules, Huisheng Oral Solution, and Jinlong Capsules in treating PLC were retrieved from CNKI, Wanfang, VIP, Web of Science, PubMed, and Cochrane Library. R 4.2 was employed to conduct a network Meta-analysis, on the basis of which the effect values of the three medicines were obtained by indirect comparison. MCDA was performed to establish the value tree based on the benefit-risk indexes. Hiview 3.2 was used to calculate the benefit values, risk values, and benefit-risk values of the three medicines in treating PLC, and a sensitivity analysis was carried out to evaluate the robustness of the results. Oracle Crystal Ball 11.1 was employed to optimize the evaluation results by Monte Carlo simulation. A total of 39 RCTs were included. The results showed that Compound Cantharis Capsules, Huisheng Oral Solution, and Jinlong Capsules combined with transcatheter arterial chemoembolization(TACE) had the benefit values of 45, 51 and 45, the risk values of 59, 47, and 41, and the benefit-risk values of 52, 49, and 43, respectively. The benefit-risk differences and [95%CI] of Compound Cantharis Capsules vs Huisheng Oral Solution, Compound Cantharis Capsules vs Jinlong Capsules, and Huisheng Oral Solution vs Jinlong Capsules were 3.00[-13.09, 21.82], 9.00[-4.39, 24.62], and 6.00[-8.84, 20.28], respectively. Based on the results of MCDA, Huisheng Oral Solution, Jinlong Capsules, and Compound Cantharis Capsules combined with TACE had the greatest benefit, the greatest risk, and the best overall benefit, respectively. Considering the efficacy and safety, the priority of the three oral Chinese patent medicines combined with TACE for treating PLC followed the trend of Compound Cantharis Capsules, Huisheng Oral Solution, and Jinlong Capsules.

Research progress and prospects of benefit-risk assessment methods for umbilical cord mesenchymal stem cell transplantation in the clinical treatment of spinal cord injury.

Over the past decade, we have witnessed the development of cell transplantation as a new strategy for repairing spinal cord injury (SCI). However, due to the complexity of the central nervous system (CNS), achieving successful clinical translation remains a significant challenge. Human umbilical cord mesenchymal stem cells (hUMSCs) possess distinct advantages, such as easy collection, lack of ethical concerns, high self-renewal ability, multilineage differentiation potential, and immunomodulatory properties. hUMSCs are promising for regenerating the injured spinal cord to a significant extent. At the same time, for advancing SCI treatment, the appropriate benefit and risk evaluation methods play a pivotal role in determining the clinical applicability of treatment plans. Hence, this study discusses the advantages and risks of hUMSCs in SCI treatment across four dimensions-comprehensive evaluation of motor and sensory function, imaging, electrophysiology, and autonomic nervous system (ANS) function-aiming to improve the rationality of relevant clinical research and the feasibility of clinical translation.

Guidance on risk-benefit assessment of foods.

The EFSA Scientific Committee has updated its 2010 Guidance on risk-benefit assessment (RBA) of foods. The update addresses methodological developments and regulatory needs. While it retains the stepwise RBA approach, it provides additional methods for complex assessments, such as multiple chemical hazards and all relevant health effects impacting different population subgroups. The updated guidance includes approaches for systematic identification, prioritisation and selection of hazardous and beneficial food components. It also offers updates relevant to characterising adverse and beneficial effects, such as measures of effect size and dose-response modelling. The guidance expands options for characterising risks and benefits, incorporating variability, uncertainty, severity categorisation and ranking of different (beneficial or adverse) effects. The impact of different types of health effects is assessed qualitatively or quantitatively, depending on the problem formulation, scope of the RBA question and data availability. The integration of risks and benefits often involves value-based judgements and should ideally be performed with the risk-benefit manager. Metrics such as Disability-Adjusted Life Years (DALYs) and Quality-Adjusted Life Years (QALYs) can be used. Additional approaches are presented, such as probability of all relevant effects and/or effects of given severities and their integration using severity weight functions. The update includes practical guidance on reporting results, interpreting outcomes and communicating the outcome of an RBA, considering consumer perspectives and responses to advice.

Investigating Stability in Subgroup Identification for Stratified Medicine.

Subgroup analysis may be used to investigate treatment effect heterogeneity among subsets of the study population defined by baseline characteristics. Several methodologies have been proposed in recent years and with these, statistical issues such as multiplicity, complexity, and selection bias have been widely discussed. Some methods adjust for one or more of these issues; however, few of them discuss or consider the stability of the subgroup assignments. We propose exploring the stability of subgroups as a sensitivity analysis step for stratified medicine to assess the robustness of the identified subgroups besides identifying possible factors that may drive this instability. After applying Bayesian credible subgroups, a nonparametric bootstrap can be used to assess stability at subgroup-level and patient-level. Our findings illustrate that when the treatment effect is small or not so evident, patients are more likely to switch to different subgroups (jumpers) across bootstrap resamples. In contrast, when the treatment effect is large or extremely convincing, patients generally remain in the same subgroup. While the proposed subgroup stability method is illustrated through Bayesian credible subgroups method on time-to-event data, this general approach can be used with other subgroup identification methods and endpoints.

A proposal for using benefit-risk methods to improve the prominence of adverse event results when reporting trials.

Adverse events suffer from poor reporting within randomised controlled trials, despite them being crucial to the evaluation of a treatment. A recent update to the CONSORT harms checklist aims to improve reporting by providing structure and consistency to the information presented. We propose an extension wherein harms would be reported in conjunction with effectiveness outcome(s) rather than in silo to provide a more complete picture of the evidence acquired within a trial. Benefit-risk methods are designed to simultaneously consider both benefits and risks, and therefore, we believe these methods could be implemented to improve the prominence of adverse events when reporting trials. The aim of this article is to use case studies to demonstrate the practical utility of benefit-risk methods to present adverse events results alongside effectiveness results. Two randomised controlled trials have been selected as case studies, the Option-DM trial and the SANAD II trial. Using a previous review, a shortlist of 17 benefit-risk methods which could potentially be used for reporting RCTs was created. From this shortlist, three benefit-risk methods are applied across the two case studies. We selected these methods for their usefulness to achieve the aim of this paper and which are commonly used in the literature. The methods selected were the Benefit-Risk Action Team (BRAT) Framework, net clinical benefit (NCB), and the Outcome Measures in Rheumatology (OMERACT) 3 × 3 table. Results using the benefit-risk method added further context and detail to the clinical summaries made from the trials. In the case of the SANAD II trial, the clinicians concluded that despite the primary outcome being improved by the treatment, the increase in adverse events negated the improvement and the treatment was therefore not recommended. The benefit-risk methods applied to this case study outlined the data that this decision was based on in a clear and transparent way. Using benefit-risk methods to report the results of trials can increase the prominence of adverse event results by presenting them alongside the primary efficacy/effectiveness outcomes. This ensures that all the factors which would be used to determine whether a treatment would be recommended are transparent to the reader.

Assessing the benefit-risk balance of drugs. Some lessons from the COVID pandemic.

INTRODUCTION: Drug efficacy and effectiveness are assessed respectively through clinical trials and pharmaco-epidemiological studies. However, relative and absolute benefits of drugs are distinct measures that must be considered in relation to the baseline risk of disease incidence, complication or progression. On the other hand, adverse drug reactions are independent of the basic risk but depend on the characteristics of the population treated. Given these prerequisites, how can we balance the benefits and risks of drugs? AREAS COVERED: We use the example of therapeutics evaluated during Covid to describe how assessing the benefit-risk balance of drugs is a complex process. EXPERT OPINION: Clinical trials are not designed to identify rare adverse events, underscoring the necessity for a pharmacovigilance system. Evaluating the balance between the benefits and risks of drugs is an ongoing process, demanding the simultaneous analysis of data from clinical trials, potential drug-drug interactions, pharmacovigilance monitoring and pharmaco-epidemiological studies, to identify potential safety concerns. In addition, pharmacologists must play a major role in educating the general public about drugs, aiding in the accurate interpretation of the benefit-risk balance and preventing misinformation.

Patient Preferences for Benefit and Risk Associated With High Intensity Focused Ultrasound for the Ablation of Prostate Tissue in Men With Localized Prostate Cancer.

INTRODUCTION: Food and Drug Administration must make decisions about emerging high intensity focused ultrasound (HIFU) devices that may lack relevant clinical oncologic data but present with known side effects. This study aims to capture patients' perspective by quantifying their preferences regarding the available benefit and important side effects associated with HIFU for localized prostate cancer. MATERIALS AND METHODS: Preferences for HIFU outcomes were examined using a discrete choice experiment survey. Participants were asked to choose a preferred treatment option in 9 choice questions. Each included a pair of hypothetical treatment profiles that have similar attributes/outcomes with varying levels. Outcomes included prostate biopsy outcome and treatment-related risks of erectile dysfunction (ED) and urinary incontinence (UI). We calculated the maximum risk of side effect patients were willing to tolerate in exchange for increased benefit. Preferences were further explored via clinical and demographic data. RESULTS: About 223 subjects with a mean age of 64.8 years completed the survey. Respondents were willing to accept a 1.51%-point increase in new ED risk for a 1%-point increase in favorable biopsy outcome. They were also willing to accept a 0.93%-point increase in new UI risk for a 1%-point increase in biopsy outcome. Subjects who perceived their cancer to be more aggressive had higher risk tolerance for UI. Younger men were willing to tolerate less ED risk than older men. Respondents with greater than college level of education had a lower risk tolerance for ED or UI. CONCLUSIONS: Results may inform development and regulatory evaluation for future HIFU ablation devices by providing supplemental information from the patient perspective.

Fertility preservation before cancer treatment: the dilemma of saying 'no' as the price of glory.

A great deal of work has been carried out by professionals in reproductive medicine in order to raise awareness about fertility preservation (FP) techniques, particularly for women, and to ensure that FP is included in the care of young adults treated for cancer or a pathology requiring gonadotoxic treatment. If the importance of the development of our discipline is obvious, our militancy in favour of FP and our emotional projections must not make us forget that medical thinking must be carried out not only on a case-by-case basis, weighing up the benefit-risk balance, but also without losing sight that conceiving a child with one's own gametes is not a vital issue. The cultural importance given to the genetic link with offspring may bias patients' and physicians' decisions, while other ways of achieving parenthood exist, and are often more effective. Systematic information should be provided on the existence of FP techniques, but this should not lead to their systematic implementation, nor should it obscure that early information will also allow patients to begin projecting themselves in alternative options to become parents.