Temporal Layering: How past, future and present intersect in the valuation of pharmaceutical innovation

This paper reflects on the challenges of writing long conceptual histories of sexual medicine, drawing on the approaches of Michel Foucault and of Reinhart Koselleck. Foucault’s statements about nineteenth-century rupture considered alongside his later-life emphasis on long conceptual continuities implied something similar to Koselleck’s own accommodation of different kinds of historical inheritances expressed as multiple ‘temporal layers.’ The layering model in the history of concepts may be useful for complicating the historical periodizations commonly invoked by historians of sexuality, overcoming historiographic temptations to reduce complex cultural and intellectual phenomena to a unified Zeitgeist. The paper also shows that a haunting reference to ‘concepts’ among scholars of the long history of sexual medicine indicates the emergence of a de facto methodology of conceptual history, albeit one in need of further refinement. It is proposed that reading Koselleck alongside Foucault provides a useful starting-point for precisely this kind of theoretical development.

Traditional agenda-setting research often focuses on the most urgent problems that dominate present public agendas. Challenging the prevalent conflation of importance with urgency in agenda-setting research, this article proposes a shift from a singular to a layered temporal conceptualization of public agendas. The suggested framework distinguishes between the immediate agenda, which addresses problems perceived as most urgent, and the delayed agenda, which focuses on issues deemed most important for the future. Enriching agenda-setting theory with insights from construal level theory, the study examines the psychological and media-related factors shaping the placement of topics on these agendas. Drawing upon original survey data and a large-scale news content analysis from the French 2022 Presidential Elections, as well as survey data from the 2023 to 2024 war in Israel and Gaza, the findings provide empirical support for the proposed framework. The results indicate that participants prioritize psychologically proximate issues on the immediate agenda, whereas psychologically distant issues gain importance on the delayed agenda. Additionally, we identify media agenda-setting effects that extend beyond the immediate temporal layer. Specifically, both studies provide evidence for a media priming effect, where news exposure increases issue salience without affecting temporal layering. The Israeli case reveals additional initial evidence for an urgency effect, where news exposure boosts issue salience of some issues primarily on the immediate agenda. Overall, the study contributes to a deeper understanding of public agendas and news media effects, introducing a temporally nuanced perspective that enriches classical approaches to agenda-setting research.

<p>Pride is notable for its dynamic treatment of time, which is key both to its appeal as a film and to its presentation of the processes of political change. By combining nostalgia, retro, and heritage, Pride manifests an artistic practice I refer to as temporal layering, which draws attention to how any single moment implies potential relationships with numerous interacting others. I use this notion to understand both the role that the 1984-5 miners' strike assumes in cultural revisions of the 1980s, and the kind of cinematic past that Pride presents. This past can be understood as a development in the heritage genre appropriate to reimagining modern British history, especially that of the 1980s, that could be called retro-heritage. By paying attention to the varied temporal layers thus present in Pride, a new perspective is offered on how nostalgia's presumed conservatism sits alongside the 'left-wing melancholy' (Traverso, 2017) that has dominated in the era of defeats since the 1980s. My ultimate aim is to ask what potential nostalgia may have when envisaging a different future.</p>

In recent years, there has been more emphasis on determining the total value of a drug product, which includes safety and efficacy information and clinical and economic value relative to other therapies. The Academy of Managed Care Pharmacy (AMCP) Format for Formulary Submissions was intended as a tool to assist health care providers in evaluating and selecting drug products. The purpose of this research was to gain the perspectives of a sample of managed care organizations (MCOs) and pharmaceutical manufacturers regarding the AMCP Format submission and evaluation process, as well as their comments on possible future direction for these guidelines as an important part of the formulary decision-making process. A random sample of large (>1 million lives) and small (<1 million lives) MCOs was generated using telephone numbers from the National Directory of Managed Care Organizations' database. Pharmaceutical manufacturer respondents were identified from the Pharmaceutical Research and Manufacturers of America (PhRMA) Foundation's Health Outcomes Committee. Telephone interviews were conducted by 2 researchers between September 2004 and October 2005. Respondents from both pharmaceutical manufacturers and MCOs nationwide were familiar with the AMCP dossier preparation and review process, allowing us to compare perspectives from each group. The interview was designed to assess the following key areas: economic models, organizational burden, confidentiality, overall value, and future expectations. Representatives from 20 MCOs and 7 pharmaceutical manufacturers completed the interview; 21 MCO representatives refused to participate, citing company policy. Nearly all (87.5%) of the MCO personnel contacted reviewed dossiers within their organization. However, MCO respondents indicated that only 40% of all drugs they reviewed included dossiers from the manufacturers. For drug evaluation at the level of the pharmacy and therapeutics committee, we found that drugs were compared with a variety of products, with 11 respondents reporting comparisons with a placebo, and all respondents reporting a comparison with at least 1 other branded product. On average, 53.5% of the dossiers MCOs received included budget-impact models, and 39.3% included cost-effectiveness analyses (CEAs) or cost-benefit analyses. Of the dossiers with economic models, less than half (46.2%) were deemed adequate. Nearly two thirds of MCO respondents reported that they modified the provided model with their own population statistics, as many reported that manufacturers do not make models directly applicable to their health plan population. The perspectives of the pharmaceutical manufacturers varied dramatically from the MCO respondents with regard to the inclusion of economic models. Five of the 7 respondents indicated that their companies always included an economic model in the submitted dossiers. One respondent indicated that 85% of company dossiers included models, and another reported that 50% of dossiers included CEA models. Both MCOs and pharmaceutical manufacturers commented that organizational burden was high, with 70% of both groups reporting the use of outside consultants to assist in the dossier process. Overall, findings for this study suggest that awareness of the AMCP Format is high among MCOs and pharmaceutical manufacturers, but aligning objectives between the 2 organization types is necessary. Conceptually, proving a drug value beyond what the U.S. Food and Drug Administration requires is a reasonable request, something most respondents agreed on. However, less than half of all drugs reviewed had a dossier. In contrast to MCO respondents, pharmaceutical manufacturers appear to have a more positive outlook on the role of the AMCP Format in effectively communicating the value of a new drug product. Further steps need to be taken to improve acceptance and integration of the AMCP Format.

Gene Therapy for Leber Hereditary Optic Neuropathy: Low- and Medium-Dose Visual Results

Rare diseases are frequently life-threatening or chronically debilitating and the impact on the quality of life of affected patients and their family members is thus significant. However, drug development for these conditions has been limited by a lack of understanding of the underlying mechanisms of disease and the relative unavailability of subjects for clinical trials, as well as the prohibitive cost of investing in a novel pharmaceutical agent with poor market potential. Nevertheless, the introduction of Orphan Drug legislations has provided important incentives for the development of orphan drugs (i.e. drugs that have been abandoned or 'orphaned' by major drug companies). Moreover, recent studies on rare diseases, including inherited immunodeficiencies and metabolic disorders, have served not only to alleviate the plight of patients with rare diseases, but also yielded valuable information on biological processes of relevance for other, more common conditions. These lessons, along with the crucial importance of cooperation between academic institutions, pharmaceutical companies, patient advocacy groups and society in the elucidation of rare diseases, are highlighted in the present review.

Health Equity in Sickle Cell Research and Access to Therapy

From Lipoproteins to Chondrocytes: A Brief Summary of the European Medicines Agency's Regulatory Guidelines for Advanced Therapy Medicinal Products

The aim . To describe the key characteristics of medical products approved by the Food and Drug Administration (FDA) and released by pharmaceutical companies from 2012 to 2024. Materials and methods. The analysis is based on data from FDA publications related to the approval of medical products from 2012 to 2024. The products were systematized by year, pathway and reason for approval, nature of the active substance (synthetic, semi-synthetic, natural or biological) and target disease (indication for use) in accordance with the codes of the Anatomical Therapeutic Chemical (ATC) classification. Results . During the analyzed period, the FDA approved a significant number of medicines, while maintaining a stable proportion of small molecules with a significant upward trend in the number of approved biologicals (monoclonal antibodies, CAR-T, siRNA, gene therapy, etc.). The largest proportion was accounted for by antitumor drugs and immunomodulators (group L according to ATC), demonstrating steady growth with projected growth in the future. Interest in drugs for the treatment of metabolic disorders and diseases of the nervous system remained steadily high, with the emergence of innovative therapeutic approaches. A gradual increase in the number of repositionings and extensions of indications was noted. The COVID-19 pandemic did not have a significant impact on the overall structure of approvals, and only two specific medicines for the treatment of COVID-19 were approved. There has been an increase in approvals for orphan diseases and the emergence of innovative therapeutic approaches: gene therapy, RNA interference, cell technologies, and bispecific antibodies. Conclusion. In the period from 2012 to 2024, the pharmaceutical industry has seen a fundamental shift towards biotechnological development methods, personalized medicine, and targeted therapy. During the period under review, the proportion of small molecule approvals remained fairly stable, but a steady (compared to previous periods) increase in the number of biotechnology product approvals (monoclonal antibodies, gene and RNA therapy) can be noted. The largest increase was noted in class L (antitumor drugs and immunomodulators), which reflects the focus of global pharmaceutical companies on the fundamental study and discovery of pharmacotherapy opportunities in the oncology and immunity. It is necessary to note the trend towards the development of drugs for the treatment of rare (orphan) diseases. In the field of therapy for metabolic disorders, during the specified period, drugs were approved that revolutionized understanding of an entire cluster of diseases and approaches to therapy, and a new standard of therapy was formed due to SGLT2 inhibitors and agonists of the incretin system receptors, including molecules with a multi-targeted effect. The COVID-19 pandemic led to a limited number of drug approvals for the treatment of this infection but thanks to it, the “door” to the development of new generation vaccines has been opened, which are largely fundamentally different from those currently existing. The discovery of new means to combat infectious agents of various nature (bacteria, protozoa, viruses, fungi, and parasites) is also one of the priority goals of pharmaceutical companies, as evidenced by a significant proportion of approvals of drugs with a similar effect. In terms of “reasons for registration,” the main share fell on original drugs; the contribution of new combinations and dosage forms was at its peak in the middle of the period and then decreased. Due to the expiration of patent protection for many drugs and the accumulation of data on their effects in the post-marketing period, a gradual increase in the number of repositionings and extensions of indications can be logically noted.

A New Frontier in the Fight Against Cancer (That Is, for Those Who Can Afford It): The Approval and Cost of CAR T-Cell Therapies

Gene and Cell Therapy Funding Opportunities in Horizon 2020: An Overview for 2014–2015

U.S-Based Community Oncologists/Hematologists' Perceptions Regarding Future Use of Gene Therapies for Patients with Hematological Disorders

Improving the informed consent process for people living with haemophilia considering gene therapy. Gene therapy is the process of replacing faulty genes with healthy ones. In haemophilia, gene therapy involves introducing a working copy of the gene for the clotting factor that patients are missing. Following treatment, patients should begin producing their own clotting factor normally. However, people living with haemophilia (PwH) need to be fully informed regarding the potential benefits and risks of gene therapy and what this means for them, whether as part of a research study or routine medical care.Patients must be respected and supported to make decisions about their own health and wellbeing, recognising their legal and moral right to set personal goals and make treatment choices. For this to happen in practice, patients should be aware of their individual health needs, understand the effects of treatment and consider lifestyle preferences in relation to their decisions. This article attempts to describe how informed consent is obtained in haemophilia gene therapy clinical trials, what affects a patient's ability to make decisions and the availability of information and support to respect and protect the interests of PwH.Regulators responsible for approving medical products have published guidance on informed consent for physicians and pharmaceutical manufacturers in haemophilia, including for gene therapy. Recommendations have been made about the best ways for PwH to discuss gene therapy with their physicians. Yet, poor communication of complex topics, such as gene therapy, can be problematic, especially if patients lack the skills and confidence to understand and discuss the science, or for physicians with limited time in clinic.We propose strategies to improve the consent process, so patients can feel more able to make informed decisions about new treatments. Further research is needed to find new, creative approaches for educating patients and ensuring that the informed consent process for gene therapy in haemophilia is ethical.

We provide an overview of the latest developments in cancer gene therapy--from the bench to early-stage clinical trials. We describe the most recent work of worldwide teams including experienced scientists and clinicians, reflecting the recent emergence of gene therapy from the 'Valley of Death'. The treatment efficacy of clinical gene therapy has now been shown in a number of diseases including cancer and we are observing a renewed interest by big pharmaceutical and biotechnology companies most obviously demonstrated by Amgen's acquisition of Biovex for up to USD$1 billion. There is an opportunity to be cautiously hopeful regarding the future of gene therapy in the clinic and we review here some of the most recent progress in the field.

Towards routine manufacturing of gene therapy drugs