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BACKGROUND: There is a pressing need to improve the accuracy of rare disease clinical study endpoints. Neutral theory, first described here, can be used to assess the accuracy of endpoints and improve their selection in rare disease clinical studies, reducing the risk of patient misclassification. METHODS: Neutral theory was used to assess the accuracy of rare disease clinical study endpoints and the resulting probability of false positive and false negative classifications at different disease prevalence rates. Search strings were extracted from the Orphanet Register of Rare Diseases using a proprietary algorithm to conduct a systematic review of studies published until January 2021. Overall, 11 rare diseases with one disease-specific disease severity scale (133 studies) and 12 rare diseases with more than one disease-specific disease severity scale (483 studies) were included. All indicators from clinical studies were extracted, and Neutral theory was used to calculate their match to disease-specific disease severity scales, which were used as surrogates for the disease phenotype. For those with more than one disease-severity scale, endpoints were compared with the first disease-specific disease severity scale and a composite of all later scales. A Neutrality score of > 1.50 was considered acceptable. RESULTS: Around half the clinical studies for half the rare diseases with one disease-specific disease severity score (palmoplantar psoriasis, achalasia, systemic lupus erythematosus, systemic sclerosis and Fournier's gangrene) met the threshold for an acceptable match to the disease phenotype, one rare disease (Guillain-Barré syndrome) had one study with an acceptable match, and four diseases (Behcet's syndrome, Creutzfeldt-Jakob disease, atypical hemolytic uremic syndrome and Prader-Willi syndrome) had no studies. Clinical study endpoints in almost half the rare diseases with more than one disease-specific DSS (acromegaly, amyotrophic lateral sclerosis, cystic fibrosis, Fabry disease and juvenile rheumatoid arthritis) were a better match to the composite, while endpoints in the remaining rare diseases (Charcot Marie Tooth disease, Gaucher disease Type I, Huntington's disease, Sjogren's syndrome and Tourette syndrome) were a worse match. Misclassifications varied with increasing disease prevalence. CONCLUSIONS: Neutral theory confirmed that disease-severity measurement needs improvement in rare disease clinical studies, especially for some diseases, and suggested that the potential for accuracy increases as the body of knowledge on a disease increases. Using Neutral theory to benchmark disease-severity measurement in rare disease clinical studies may reduce the risk of misclassification, ensuring that recruitment and treatment effect assessment optimise medicine adoption and benefit patients.
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Determinação de Ponto Final , Doenças Raras , Humanos , Doenças Raras/diagnóstico , Doenças Raras/epidemiologia , Estudos Clínicos como AssuntoRESUMO
BACKGROUND: Health-related quality of life (HRQoL) tools are limited by the indicators included in the construct and variation in interpretation by different researchers. Neutral Theory describes the ideal construct that includes all relevant indicators and, therefore, complete accuracy, or neutrality. Neutral Theory can thereby provide the framework to develop or test constructs. To assess the application of Neutral Theory, the neutrality of generic tools (SF-36 and EQ-5D) at measuring HRQoL was compared to disease/condition-specific tools, with the latter considered surrogates for the Neutral construct. METHODS: Full descriptions of all disease/condition-specific HRQoL tools published on PubMed (to 01-Jul-19) were sourced. For each tool, the number of items with and without a direct match within the SF-36 and EQ-5D was recorded and the sensitivity/specificity calculated. RESULTS: The SF-36 and EQ-5D did not achieve a sensitivity/specificity both > 50% against any of the 163 disease/condition-specific tools identified. At 20% prevalence of poor HRQoL, the false positive rate (FPR) was > 75% for all but two tools against the SF-36 and six tools against the EQ-5D. Increasing poor HRQoL to 80%, 47 tools for the SF-36 and 48 tools for the EQ-5D had a FPR < 50%. For rare disease tools (< 1/2000 population; n = 17), sensitivity/specificity ranged from 0 to 40%/5-31% for the SF-36 and 0-22%/29-100% for the EQ-5D. For non-rare (n = 75) and symptom-specific tools (n = 71) sensitivity/specificity was: 0-100%/0-100% (SF-36) and 0-50%/0-100% (EQ-5D); and 0-60%/0-19% (SF-36) and 0-25%/0-100% (EQ-5D), respectively. No concordance was recorded for 18% (2/11) of results from studies of rare disease tools versus the SF-36 (no data vs EQ-5D). For non-rare, disease-specific tools, results were discordant for 30% (25/84) and 35% (23/65) of studies against the SF-36 and EQ-5D, respectively. For symptom-specific tools, corresponding results were 36% (24/66) and 16% (5/31). CONCLUSIONS: Generic HRQoL tools appear poorly correlated with disease/condition-specific tools, which indicates that adoption of Neutral Theory in the development and assessment of HRQoL tools could improve their relevance, accuracy, and utility in economic evaluations of health interventions.
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Qualidade de Vida , Análise Custo-Benefício , Humanos , PsicometriaRESUMO
BACKGROUND: The novel coronavirus (SARS-CoV-2) has led to a global pandemic, resulting in a disease termed COVID-19, which commonly presents in adults as a typical infection of the upper respiratory tract. Although the disease is often acute, one in ten patients can continue to be affected for weeks or months, resulting in a state called long COVID. Existing evidence suggests there are no patient-centred instruments for capturing the impact of long COVID on the quality of life of people affected. METHODS: The Jandhyala Method was used to identify indicators of long COVID quality of life. The resulting post-acute (long) COVID-19 Quality of Life (PAC-19QoL) instrument was validated with a control group of unaffected participants and finally implemented in the dedicated patient registry, PAC-19QoLReg. PARTICIPANTS: 15 participants suffering from long COVID, who have been positively diagnosed with COVID-19, either via diagnostic or antibody tests and a validation control group of 16 healthy participants who have not suffered from COVID-19. MAIN OUTCOME MEASURES: Indicators submitted by participants with long COVID that address the specific impact of the illness on their quality of life. RESULTS: Forty-four Quality of Life Indicators (QoLI) across four domains, namely, psychological, physical, social, and work, were agreed by the participants with long COVID to be relevant for the assessment of their quality of life (CI > 0.5). The validation stage identified 35/44 QoLIs that differentiated between the two groups, with a statistically significant difference between the mean QoLI Likert Scores (p < 0.05). CONCLUSIONS: The PAC-19QoL instrument and PAC-19QoLReg prospective observational cohort clinical study will enable an understanding of disease progression, on and off treatment, on the quality of life of patients with long COVID beyond simple symptomatology. TRIAL REGISTRATION: ClinicalTrials.gov Identifier NCT04586413; 14th October 2020.
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COVID-19 , Qualidade de Vida , COVID-19/complicações , Humanos , Pandemias , SARS-CoV-2 , Resultado do Tratamento , Síndrome de COVID-19 Pós-AgudaRESUMO
BACKGROUND: Influenza is associated with significant disease burden in the US and is currently best controlled by vaccination programs. Influenza vaccine effectiveness (VE) is low and may be reduced by several factors, including egg adaptations. Although non-egg-based influenza vaccines reportedly have greater VE in egg-adapted seasons, evidence for egg adaptations' reduction of VE is indirect and dissociated, apart from two previous European consensuses. METHODS: This study replicated the methodology used in a 2020 literature review and European consensus, providing an updated review and consensus opinion of 10 US experts on the evidence for a mechanistic basis for reduction of VE due to egg-based manufacturing methods. A mechanistic basis was assumed if sufficient evidence was found for underlying principles proposed to give rise to such an effect. Evidence for each principle was brought forward from the 2020 review and identified here by structured literature review and expert panel. Experts rated the strength of support for each principle and a mechanistic basis for reduction of VE due to egg-based influenza vaccine manufacture in a consensus method (consensus for strong/very strong evidence = ≥ 3.5 on 5-point Likert scale). RESULTS: Experts assessed 251 references (from previous study: 185; this study: 66). The majority of references for all underlying principles were rated as strong or very strong supporting evidence (52-86%). Global surveillance, WHO candidate vaccine virus selection, and manufacturing stages involving eggs were identified as most likely to impact influenza VE. CONCLUSION: After review of extensive evidence for reduction of VE due to egg-based influenza vaccine manufacture, influenza experts in the US joined those in Europe in unanimous agreement for a mechanistic basis for the effect. Vaccine providers and administrators should consider use of non-egg-based influenza vaccine manufacture to reduce the risk of egg adaptations and likely impact on VE.
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Vacinas contra Influenza , Influenza Humana , Humanos , Influenza Humana/epidemiologia , Consenso , Eficácia de Vacinas , Europa (Continente) , Estações do Ano , Vacinação/métodosRESUMO
OBJECTIVE: Current cost-effectiveness analyses (CEA) emphasize drug costs as the differentiator between NICE recommended anti-VEGF treatments but may neglect real-world non-drug costs of running nAMD services in the UK. To address this, this study identified real-world non-drug service cost items relevant to UK NHS nAMD clinics, including costs arising from operational strain (demand exceeding capacity). METHODS: Cost items were identified by a structured literature review of peer-reviewed and grey literature, and an expert panel of 10 UK-based ophthalmologists with relevance to real-world practice. These items underwent meta-synthesis and were then determined in a consensus exercise. RESULTS: Of 237 cost items identified, 217 (91.6%) met the consensus threshold of >0.51 and were included in the nAMD Service Non-Drug Cost Instrument (nAS). Sensitivity of cost items taken from UK Health Technology Assessment (HTA) using the nAS as the reference standard was low (HTAmin: 1.84%, 95% CI 0.50-4.65%; HTAmax: 70.51%, 95% CI 63.96-76.49%). False negative rates showed variable likelihood of misclassifying a service by cost burden depending on prevalence. Scenario analysis using cost magnitudes estimated annual per-patient clinic cost at £845 (within capacity) to £13,960 (under strain) compared to an HTAmin estimate of £210. Accounting for cost of strain under an assumed 50% increase in health resource utilization influenced cost-effectiveness in a hypothetical genericisation scenario. CONCLUSION: Findings suggested that HTA underestimates UK NHS nAMD clinic cost burden with cost of strain contributing substantial additional unmeasured expense with impact on CEA. Given potential undertreatment due to strain, durability is suggested as one of the relevant factors in CEA of nAMD anti-VEGF treatments due to robustness under limited capacity conditions affecting UK ophthalmology services.
When considering how well treatments work versus how much they cost, the focus is usually only on the price of the medicine itself. However, other real-world costs exist. In the UK, when treating certain eye problems such as neovascular age-related macular degeneration (nAMD), there are additional expenses related to running clinics and managing treatments that often go unnoticed. To get a better understanding of these hidden costs, the study examined factors like clinic workload and the extra expenses that come with it. Ten eye doctors in the UK were consulted for their expert opinions and numerous research papers were reviewed to identify these additional costs. The study grouped different costs in a tool called the nAMD Service Non-Drug Cost Instrument (nAS). When the findings of the nAS tool were compared to the usual methods of calculating costs, it was found that the conventional approach overlooked many of the actual expenses. Busy clinics face unique challenges, such as higher operational costs associated with staffing for extended hours, emergency appointments, extended waiting times and the potential to miss optimal treatment windows. This can lead to disease progression and the onset of comorbidities, which require more complex and costly treatments. Recognizing these real costs is crucial when making decisions about treatments, especially when treatments require more frequent visits to eye clinics. This study emphasizes the importance of considering all expenses, not just the obvious ones like medication and doctor visits when determining the most effective way to manage eye conditions like nAMD in the UK.
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Análise Custo-Benefício , Humanos , Reino Unido , Custos de Cuidados de Saúde/estatística & dados numéricos , Inibidores da Angiogênese/economia , Inibidores da Angiogênese/uso terapêuticoRESUMO
BACKGROUND: Despite the escalating number of patients undergoing aesthetic BoNT-A procedures, a standardized, objective means of setting treatment goals and measuring the success of treatment is lacking. Treat-To-Goal (TTG) is a new approach to consent that utilizes the Merz Aesthetics Scale to set objectively defined start points and treatment goals to better inform the consent process and provide a means of measuring the success of treatment. OBJECTIVE: To evaluate the TTG approach vs standard consent procedures in terms of patient understanding of the risks and benefits of treatment. METHODS: This study was undertaken in 2 phases among consecutive patients presenting for BoNT-A treatment. Phase 1 consisted of a crossover comparison of patient satisfaction with standard consent vs the TTG approach (n=20). Patient understanding of the likely outcomes and risks associated with treatment following consent and their overall preference were assessed using 10-point visual analog scales (VAS). Phase 2 assigned patients to receive no treatment (n=10) or treatment with BoNT-A (n=54) following consent with the TTG approach. Patients were followed up with 28 days later to assess whether the goals defined during consent had been met. RESULTS: The TTG approach significantly improved patient understanding of likely outcomes of BoNT-A treatment compared with standard consent (P=.004 when standard consent assessed first, and P=.002 when TTG assessed first). All patients assessed preferred the TTG approach (median VAS score in favor of TTG: 7.0, P<.0001). Target improvements were successfully met or exceeded in at least one treatment area (forehead, glabellar lines, crow's feet) in all patients treated with BoNT-A. In contrast, none of the untreated patients met their target improvements unless the target was defined as no change. CONCLUSION: The TTG approach represents a significant improvement over standard consent in terms of the information it provides to patients. Further investigation of this concept is warranted.
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Toxinas Botulínicas Tipo A/uso terapêutico , Consentimento Livre e Esclarecido/normas , Fármacos Neuromusculares/uso terapêutico , Adulto , Interpretação Estatística de Dados , Estética , Face , Feminino , Objetivos , Humanos , Masculino , Pessoa de Meia-Idade , Satisfação do Paciente , Melhoria de Qualidade , Reprodutibilidade dos Testes , Risco , Pele/patologia , Envelhecimento da Pele , Resultado do Tratamento , Adulto JovemRESUMO
OBJECTIVE: Regulatory use of real-world evidence (RWE) has been recognized as a useful supplement to clinical trial evidence and could benefit patients by reducing time to treatment. However, commercial benefits have not been documented. The aim was to determine commercial impact of regulatory RWE, using ambrisentan as an illustrative example. METHODS: A Markovian-like transition model was constructed to simulate the drug development workflow across a simulation time of t = 20 years. RWE was assumed to be incorporated at pII-pIII and pII-pIII-pIV, and its multiplicative median transition rate was determined by biopharma expert opinion. Each model was subjected to "with" and "without" RWE rates. Commercial impact was estimated using potential decrease in time to launch. Time to first medicine adoption and potential lives saved were also estimated. RESULTS: Based on cumulative first prescriptions for ambrisentan among pulmonary arterial hypertension patients (N = 487), in comparison to standard drug development, RWE incorporation has the potential to expedite first medicine adoption by 10.4 weeks. The duration of market launch was estimated at 2.5-3.0 years earlier than standard, and approximately 9% of patients would benefit in survival. Potential earnings for an earlier launch would be GBP £43,597.86 per patient, with launch being brought forward from 2009 to 2007. CONCLUSIONS: Regulatory RWE has the potential to increase overall survival rates and potential earnings by reducing time to launch. This study provides further support for industry efforts to generate RWE in time for regulatory approval.
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Aprovação de Drogas , Desenvolvimento de Medicamentos , Humanos , Ensaios Clínicos como AssuntoRESUMO
BACKGROUND: Medical affairs pharmaceutical physicians (MAPPs) are at risk for low work-related quality of life (WRQoL). The aim of this study was to develop, validate and implement the first WRQoL instrument for this population. METHODS: A prospective observational cohort clinical study, the Medical Affairs Pharmaceutical Physician Work-related Quality of Life (MAPPWrQoL) Instrument Development and Patient Registry (MAPPWrQoLReg), was registered in November 2021 (NCT05123846). Thirteen MAPPs and 12 non-MAPPs participated in development and validation between December 2021 and January 2022. Development used the Jandhyala method for observing proportional group awareness and consensus. Discriminant validity analysis used the WRQoL Scale as a reference standard and assessed whether the instrument could differentiate between the groups. Twelve MAPPs and 12 non-MAPPs self-reported their WRQoL in the registry each month from February 2022. Recruitment and data collection are ongoing; 6-month data between February 2022 and August 2022 are reported here. RESULTS: Two participants were excluded from the registry. Chi-squared analysis showed a significant difference between the MAPPWRQoL instrument and WRQoL Scale (p = 1.029e-08) with acceptable sensitivity (89.19%) and specificity (75.00%). There were significant between-group differences for total scores at each follow-up (p = .003; n = 6 questions). Chi-squared analysis showed a significant difference between MAPPs' and non-MAPPs' ability to answer MAPPWRQoL instrument items (p = .002629), with acceptable sensitivity (91.9%) and near-acceptable specificity (66.7%). MAPPs' WRQoL did not change significantly over 6 months. CONCLUSION: Discriminant validity of the 39-item MAPPWRQoL instrument was confirmed. The Jandhyala method successfully developed and validated a specific WRQoL instrument and may be applied to similar populations, such as junior doctors and UK general practitioners.
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Clínicos Gerais , Qualidade de Vida , Humanos , Inquéritos e Questionários , Autorrelato , Preparações Farmacêuticas , Reprodutibilidade dos TestesRESUMO
OBJECTIVE: Low rates of inclusion of real-world evidence (RWE) during regulation may arise from lack of clarity and consensus on its definition. A conceptually mature definition of RWE may have pragmatic utility, increasing its inclusion during regulation. The aim was to develop a definition of RWE to promote inclusion in regulatory submissions and assess its conceptual maturity. METHODS: Thirteen medical affairs pharmaceutical physicians completed two qualitative online surveys to generate items needed in a definition of RWE. Items that reached a consensus index of > 50% (CI > = 0.51) were retained in the final definition. The maturity of the definition was assessed using concept analysis. RESULTS: After attrition, 11 participants completed the study and generated 18 items to be included in a definition of RWE. All items reached the consensus threshold and were included. The definition was conceptually mature on three of the four dimensions: the potential for a consensual definition across stakeholders, a description of its characteristics and clear preconditions and outcomes. Further research is needed to delineate the boundaries of RWE. CONCLUSIONS: A definition of RWE was generated that may increase its inclusion during medicines regulation, especially with further refinement from regulators and other stakeholders.
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Médicos , Humanos , Consenso , Preparações FarmacêuticasRESUMO
BACKGROUND: The pharmaceutical industry requires a highly qualified workforce with diverse skillsets. Medical affairs pharmaceutical physicians (MAPPs) have unique qualifications among pharmaceutical company employees, but the exact contribution of their education and training is unknown. This study aimed to identify the medical education and training competencies MAPPs use in the pharmaceutical industry in relation to the four external stakeholders, regulators, payors, prescribers, and patients. METHOD: Ten MAPPs were recruited using convenience sampling via professional networks. A systematic literature review and the Jandhyala method, a two-stage qualitative online consensus method, identified which of MAPPs' medical education and training competencies they used in their work with each external stakeholder. Statistical analyses determined heterogeneity in the relevance of competencies and competency categories to each stakeholder. RESULTS: Nine MAPPs completed the study. Of the 59 competencies identified, 54 were relevant to all external stakeholders. Relevance of competencies varied significantly between external stakeholders (p = .0434). Binary competency scores varied significantly for three pairs of stakeholders, "patient vs. payor" (p = .025), "prescriber vs. regulator" (p = .013) and "prescriber vs. payor" (p = .008). Between-stakeholder overall frequency count varied significantly for two of the nine competency categories. CONCLUSION: MAPPs develop a highly specialized set of competencies during medical education and training from which they use distinct subsets to meet the needs of external stakeholders in the pharmaceutical industry. Undergraduate and postgraduate competency-based medical education appears to prepare MAPPs for cognitive and technical work. Further exploration may aid understanding of how they develop soft skills.
Medical affairs pharmaceutical physicians (MAPPs) are of key importance in promoting patient centricity in the pharmaceutical industry. Their competency-based medical education and clinical experience give them a unique skillset among pharmaceutical company employees. MAPPs utilize their training to benefit pharmaceutical companies as well as the four external stakeholders in medicine adoption: regulators, payors, prescribers and patients. Previous work has suggested that their education and training may account for their ability to benefit all external stakeholders; however, this has not been explored in detail. The aim of this study was to identify competencies MAPPs develop during medical education, training and clinical experience and which of these they use in their work with each of the four external stakeholders.To do this, first, we reviewed the literature and asked MAPPs to self-report the competencies they developed during medical education and training, and which were relevant to their work with each of the four stakeholders. We found that 54 of the 59 identified competencies were relevant to work with all external stakeholders. However, the relevance of individual competencies varied between external stakeholders, with further analysis showing that the difference appeared to be accounted for by differences between three main pairs of stakeholders. These were "patient vs. payor", "prescriber vs. regulator" and "prescriber vs. payor. In other words, MAPPs were likely to use different competencies in their work with each stakeholder. With our analysis of competency categories, we concluded that MAPPs use a highly specialized combination of competencies adapted to each external stakeholder.
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Competência Clínica , Médicos , Humanos , Prova Pericial , Indústria Farmacêutica , Preparações FarmacêuticasRESUMO
BACKGROUND: Priority setting in health research has been described as essential due to disparities within and between countries and populations. Commercial benefits to the pharmaceutical industry may increase the generation and use of regulatory Real-World Evidence which has recently been reported in the literature. Research must be steered by valuable priorities. This study's objective is to identify key gaps in the knowledge of triglyceride-induced acute pancreatitis by generating a list of potential research priorities for a Hypertriglyceridemia Patient Registry. METHOD: The Jandhyala Method was used to observe the consensus of expert opinion from ten specialist clinicians in the treatment of triglyceride-induced acute pancreatitis across the US and EU. RESULTS: Ten participants completed the consensus round of the Jandhyala method and generated 38 unique items which they all agreed with. The items were included in the generation of research priorities for a hypertriglyceridemia patient registry and presented a novel application of the Jandhyala method for the development of research questions, in aid of the validation of a core dataset. CONCLUSION: The TG-IAP core dataset and research priorities combined can develop a globally harmonized framework where TG-IAP patients can be observed simultaneously using the same set of indicators. This will increase knowledge of the disease and facilitate higher-quality research by addressing issues related to incomplete data sets in observational studies. Furthermore, validation of new tools will be enabled, and diagnosis and monitoring will be improved as well as the detection of changes in disease severity and subsequent disease progression, improving the management of patients with TG-IAP overall. This will inform personalized patient management plans and improve patient outcomes along with their quality of life.
The differences in healthcare between countries and groups of people will likely affect the type of research needed. This is why people that have experience with specific diseases need to be spoken to, to understand what their concerns are. These types of people could be doctors or patients. When this information is gathered, this could help inform organizations interested in a specific disease on how to help patients in real life situations.For this study, the researchers worked with ten expert doctors who treat a disease called triglyceride-induced acute pancreatitis (TG-IAP). These doctors were from the United States and the European Union, and they were asked to share their opinions on what the most important research areas are using the Jandhyala method. The doctors generated and agreed on 38 items, all related to the most important research areas for TG-IAP.The research areas identified can be used with important data collected about patients with TG-IAP to create a study where these patients are monitored in different locations using the same measurements. This study will help people learn more about the disease and improve the quality of research by making sure the most important data is collected. As a result, patients with TG-IAP can have their healthcare improved.
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Hipertrigliceridemia , Pancreatite , Humanos , Consenso , Doença Aguda , Qualidade de Vida , Hipertrigliceridemia/diagnóstico , Hipertrigliceridemia/terapia , Pesquisa , Sistema de Registros , TriglicerídeosRESUMO
BACKGROUND: In the study on triglyceride-induced pancreatitis (TG-IAP), a core clinical dataset using the Jandhyala method was developed to collect the minimum amount of information for each patient presenting with TG-IAP globally. This approach offered a unified framework for observing multiple populations of TG-IAP patients using the same set of indicators, resulting in a considerably larger and uniform real-world population. It was understood that when this core dataset is implemented in a patient registry it could address the issue of missing data in observational studies and produce higher-quality research. In this paper, the protocol used to design and implement a patient registry for this core dataset to generate real-world evidence from multiple sites is described. METHOD: The study is designed as an international, multicenter, non-interventional, observational registry that will enroll adult patients with hypertriglyceridemia to collect natural history data on the treatment, progression, and long-term outcomes of hypertriglyceridemia-induced acute pancreatitis. Patients with both hypertriglyceridemia and pancreatitis will be invited to participate in the registry at participating hospitals and centers worldwide. DISCUSSION: Data from this registry, and others like it, is intended for healthcare providers to optimize clinical decision-making through an enhanced understanding of the variability, progression, and natural history of hypertriglyceridemia as well as the burden of disease. CONCLUSION: Global epidemiological data on hypertriglyceridemia and its role in acute pancreatitis is limited. Using real-world evidence, this registry, along with others like it, may help healthcare providers understand the variability, progression, natural history, and burden of the disease, and improve the diagnosis and management of HTG and TG-IAP.
In a 2022 study, information was collected from literature, patients, and doctors who care for patients to create a record with the most important information needed to understand patients with a disease called triglyceride-induced acute pancreatitis (TG-IAP). This type of record may help people find patients with the disease and the type of care or treatment they require. The study was started and completed because the doctors used methods to guide and help them understand what needed to be done. This paper describes the method used for this study, including information on: Data collection: how the relevant information about TG-IAP patients was collected;Permissions: how permission was gained to do the study;Patient information: how the information collected about TG-IAP patients will be used; andPatient protection: how the patients who takes part in the study will be protected.
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Hipertrigliceridemia , Pancreatite , Adulto , Humanos , Doença Aguda , Hipertrigliceridemia/complicações , Hipertrigliceridemia/epidemiologia , Hipertrigliceridemia/terapia , Estudos Multicêntricos como Assunto , Pancreatite/diagnóstico , Pancreatite/epidemiologia , Pancreatite/terapia , Estudos Prospectivos , Estudos Retrospectivos , Triglicerídeos , Estudos Observacionais como AssuntoRESUMO
OBJECTIVE: The objective of this study is to generate a core clinical dataset (CD) containing the minimum acceptable amount of information that should be collected for each patient presenting with triglyceride-induced acute pancreatitis within global treatment centres or sites. METHOD: The Jandhyala Method, including systematic literature review and SMART interviews, was used to observe expert opinion from ten leaders in the treatment of triglyceride-induced acute pancreatitis (TG-IAP) across the US and EU. RESULTS: Using the PRISMA Literature Review Protocol, data were extracted from 123 of the 6718 identified studies. A total of 243 items were identified from the data extracted from these studies and, combined with the unique items coded from the Awareness Round (1) survey, formed the Consensus Round (2) survey. One hundred and ninety-five of the 243 items (80%) met the consensus threshold and were included for appraisal in the SMART interview phase. A total of 109 items were agreed to form part of the current clinical diagnostic and monitoring procedure by all experts once the weights across all the stakeholder disciplines were balanced to eliminate bias. These items were further condensed to form the core dataset, comprising a total of 87 items. CONCLUSION: Once validated and adopted, the TG-IAP CD will improve the overall management of patients with TG-IAP by speeding up diagnosis and detecting changes in disease severity and subsequent disease progression, informing personalized patient management plans, and improving patient outcomes.
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Pancreatite , Humanos , Pancreatite/diagnóstico , Pancreatite/terapia , Doença Aguda , Triglicerídeos , Progressão da Doença , Gravidade do Paciente , Técnica DelphiRESUMO
INTRODUCTION: The post-acute (long) COVID-19 Quality of Life instrument is the only specific instrument designed to assess the quality of life in long COVID patients. The present study aims to make a transcultural adaptation and validation into Spanish of the disease-specific (long COVID) quality of life instrument, post-acute (long) COVID-19 Quality of Life, to have a tool for objective measurement of quality of life in this population. METHODS: A descriptive cross-sectional study was divided into two phases. In phase one, the translation and cultural adaptation of the questionnaire was performed, while in phase two, the questionnaire was validated. The Spanish version of the questionnaire was used with a sample of 206 people, 40 males (19.4%) and 166 females (80.6%), with an age range between 21 and 70 years old. Participants completed the questionnaire through an online platform. Internal consistency, construct validity, convergent validity, test-retest reliability, and ceiling and floor effects of the Spanish version were analyzed. RESULTS: The Spanish version of the post-acute (long) COVID-19 Quality of Life instrument showed high internal consistency, with Cronbach's alpha= 0.922 and an intraclass correlation coefficient of 0.936. Mean scores obtained in the PAC-19QoL and SF-12 questionnaires showed that those who had a worse quality of life in the SF-12 tool also a had worse quality of life in the PAC-19QoL tool. CONCLUSIONS: This study shows that the Spanish version of the post-acute (long) COVID-19 Quality of Life instrument is an appropriate and valid tool for assessing the quality of life of long COVID patients.
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COVID-19 , Qualidade de Vida , Masculino , Feminino , Humanos , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Idoso , Síndrome de COVID-19 Pós-Aguda , Reprodutibilidade dos Testes , Estudos Transversais , Inquéritos e Questionários , PsicometriaRESUMO
Botulinum neurotoxin-A (BoNT-A) has become widely used in aesthetic applications over the past 20 years with several formulations now available. Although widely assumed to be equipotent, recent claims that the original commercial formulation, onabotulinumtoxinA (Botox®/Vistabel®, Allergan UK, Marlow, UK) is more potent than incobotulinumtoxinA (Bocouture®/Xeomin®, Merz Pharma, UK) have raised concerns that clinicians may be persuaded to increase doses to the potential detriment of their patients. To investigate this further, a review of the clinical evidence for the commercially available cosmetic formulations of BoNT-A was undertaken alongside a meta-analysis, carried out using mixed treatment analysis (MTA) methodology, of the available clinical data in the aesthetic setting. This demonstrated that at a dose of 24 units, there was a 94% likelihood that incobotulinumtoxinA was more effective than onabotulinumtoxinA in achieving a response as defined in the included studies; however, the scale of this advantage was not clinically meaningful. Of 11 clinical and preclinical studies identified comparing incobotulinumtoxinA and onabotulinumtoxinA directly, the weight of evidence suggested that there was no difference in the relative potency of the two products. As such, clinicians should continue to consider the formulations to be equipotent until such time that compelling clinical evidence to the contrary becomes available.
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Toxinas Botulínicas Tipo A/administração & dosagem , Toxinas Botulínicas Tipo A/química , Animais , Química Farmacêutica , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto/métodos , Envelhecimento da Pele/efeitos dos fármacosRESUMO
BACKGROUND: A pilot study conducted in 2020 suggested that Medical Affairs Pharmaceutical Physicians (MAPPs) may be inherently undervalued within the pharmaceutical industry and vulnerable to replacement by less qualified roles. There are currently no standardized metrics to measure MAPP performance, thus it is necessary to measure the value of MAPPs to employers and clarify the need for their specific skills. OBJECTIVES: The first aim of this study was to identify a list of indicators to produce an MAPP value measurement tool, and the second aim was to determine its discriminant validity by showing that the 'MAPPval instrument' differentiated the MAPP role from other internal stakeholders (regulatory affairs, market access, commercial, and patient advocacy) in terms of accountability for pharmaceutical company activities and level of engagement with external stakeholders. METHODS: MAPPs were recruited using convenience sampling via professional networks and completed a qualitative online survey to identify a list of key role indicators using a consensus method known as the Jandhyala method. Responses were coded and scored, and aggregated responses were presented to participants in a Consensus Round. Participants rated their agreement with each item on a 5-point Likert scale, from strongly agree to strongly disagree. Indicators that reached a consensus index of > 50% (CI ≥ 0.51) were retained in the final MAPP performance instrument. Participants' retrospectively self-reported professional activities over a period of 12 months were used to validate the measure. A two-proportion z-test and Mann-Whitney tests were used to determine discriminant validity by showing whether the value of the MAPP role as defined by the instrument was significantly different from that of other internal stakeholders in terms of their accountability for and external stakeholder benefit from each MAPP activity. RESULTS: In total, 11 MAPPs participated in the Jandhyala method, which generated 22 unique MAPP value indicators. Payor-targeted activities and journal publications had the two highest awareness indexes (1.00 and 0.98, respectively). The retrospective study confirmed the MAPPval instrument's validity. MAPPs were the only internal stakeholder classified as accountable for at least one activity that benefited all four stakeholders. They were classified as accountable for activities that influenced significantly more external stakeholders than other internal stakeholders, even when activities influenced fewer than four external stakeholders. MAPPs were also accountable for significantly more activities recorded over the 12-month period than regulatory affairs, market access, commercial, and patient advocacy. CONCLUSIONS: This study generated and validated the first measure of MAPP value to pharmaceutical companies. MAPPs have unique value to pharmaceutical companies compared with other roles in terms of their accountability for activities that influence regulators, payors, prescribers, and patients. Through their accountability for pharmaceutical company activities and influence of external stakeholders, MAPPs play a key role in medicine adoption.
Assuntos
Médicos , Consenso , Humanos , Preparações Farmacêuticas , Projetos Piloto , Estudos RetrospectivosRESUMO
Background: Medical affairs pharmaceutical physicians (MAPPs) have unique value to pharmaceutical companies due to their accountability for activities that benefit regulators, payors, prescribers and patients. This study assessed whether MAPPs' specialist training and education in pharmaceutical medicine could account for this level of value by determining whether there was significant variation in education and training between MAPPs and other internal stakeholders of pharmaceutical companies. Methods: A systematic search of LinkedIn profiles from the 10 pharmaceutical companies by revenue was conducted between June and October 2021. Job title and type and year of undergraduate and postgraduate qualifications were extracted. A one-sided Mann-Whitney test assessed for differences in the total number of qualifications between MAPPs and other internal stakeholders involved in medical affairs using MAPPs as the reference group. Other internal stakeholders included medical affairs pharmacists (MAPharm), other medical affairs professionals (MAOth), and market access (MAcc), commercial (COmm) and sales professionals. Sub-group analysis determined differences in undergraduate and postgraduate education. Results: In total, 524 profiles were included. Compared to all other internal stakeholders, MAPPs had a significantly higher number of undergraduate (p < 0.001) and postgraduate (MAPharm, p = 0.003; MAOth, p = 0.004; MAcc, COmm and Sales, p < 0.001) qualifications. Additionally, MAPPs had a significantly longer time to industry than other internal stakeholders apart from MAPharm. Of those with clinical qualifications, MAPPs were almost twice as likely to have business qualifications. Conclusions: Of all internal stakeholders, MAPPs had the highest number of qualifications and the best match between expertise and the contextual demands of decision-makers in the pharmaceutical industry. Pharmaceutical companies in the UK can use these findings to clarify role boundaries and decision-making power based on the nature and level of expertise of each internal stakeholder.
Assuntos
Indústria Farmacêutica , Médicos , Humanos , Comércio , Escolaridade , Preparações FarmacêuticasRESUMO
BACKGROUND: Despite calls for the use of additional real-world evidence (RWE) during drug development, rates of inclusion at the regulatory stage remain low. The medicine adoption model suggests that providing additional RWE to regulators would result in a wider indicated population than providing randomised-controlled trial evidence (RCTE) alone. Here, we tested this hypothesis. METHODS: All engagements concerning the 88 orphan drugs approved between 2009 and 2019 on the European Medicines Agency Orphan Register were reviewed between September and December 2019. Engagements were grouped as containing either randomised-controlled trial evidence (RCTE) or RCTE with real-world evidence (RWE). The data on indicatable population (the therapeutic indication requested by an engagement) and indicated population (the therapeutic indication ultimately granted) as well as the median number of criteria limiting the indicated population in each study type (RCTE/RWE) was extracted. A chi-square test assessed the association between the indicated population (as a proportion of the indicatable population) and type of evidence (RCTE with or without RWE) and a Wilcoxon rank sum test assessed the difference between the median number of limiting criteria between RCTE and RWE studies. Prediction modelling extrapolated the results of a power analysis to a level expected to deliver significance and the time this would take. RESULTS: The review identified 103 engagements, of which three were excluded (one contained only RWE; two contained only systematic literature reviews), leaving 100 engagements for 87 orphan medicines in the final analysis. Only 13% of engagements contained RWE. Although the difference was statistically insignificant, 76.92% of engagements containing RCTE and RWE resulted in a broader indicated population as compared to only 56.32% of those that contained RCTE alone. The median number of limiting criteria from RCTE (37 (28, 43)) and RWE (5 (2, 9)) studies varied significantly (p = 0.005). Modelling suggested that the analysis would achieve sufficient power by 2033-37 at the current RWE adoption rate. CONCLUSION: The proportion of the disease population studied in RWE was greater than that in RCTE. The analysis testing the relationship between additional RWE and broader indicated population would achieve adequate power between 2032 and 2037 at the current RWE adoption rate.
RESUMO
BACKGROUND: Accurate measurement of any constructs in clinical studies is of critical importance, especially if the adoption of an intervention relies on detecting a significant treatment effect where one exists. Under Neutral theory, the amount of relevant and irrelevant indicators selected to operationalise the construct contribute equally to the accuracy of the observation. The Neutral or accurate observation is achieved by observing all relevant indicators only. Generic QoL instruments such as EQ-5D are increasingly being accepted as imprecise, especially in rare diseases, based on the relevance of their indicators. QoL is a construct that embodies a patient's subjectivity, individuality, and local circumstances at measurement. SEIQoL-DW is an instrument designed to respect these characteristics of QoL through eliciting indicators or cues directly from the subject along with the proportion of the overall QoL they contribute. EQ-5D and SEIQoL can therefore be considered as being at opposing ends of accuracy in QoL measurement. XLH is a hereditary, progressive, rare disease characterised by phosphate wasting, affecting both children and adults and impacting their QoL. The purpose of this study was to observe if any change in QoL of adult XLH patients were detectable using EQ-5D, SEIQoL eliciting new cues at each visit, and SEIQoL administering baseline cues overall visits (thereby silencing its time-dependency) versus baseline over 12 months. In addition, any association between the three sets of observations was explored. RESULTS: All quality of life scores were observed to decrease from baseline by 13.36%, 7.32% and 2.7% based on SEIQoLvisit_cues, SEIQoLbaseline_cues, and EQ-5D assessments, respectively. The decrease in the quality of life scores was only statistically significant (p = 0.037) for SEIQoLvisit_cues. Beyond the baseline visit, the only highly positive and statistically significant pairwise association was between SEIQoLvisit_cues and SEIQoLbaseline_cues at M6 (ρ = 0.782, P value < 0.05) and M9 (ρ = 0.879, P value < 0.05). CONCLUSIONS: EQ-5D and SEIQoLbaseline_cues failed to detect the same statistically significant decrease in QoL observed by SEIQoLvisit_cues. Both sets of SEIQoL observations were more closely associated with each other than with EQ-5D. Observing constructs such as QoL in rare diseases benefit from a Neutrality in indicator selection and respecting variation in dominance of various indicators over time.
Assuntos
Raquitismo Hipofosfatêmico Familiar , Qualidade de Vida , Adulto , Criança , Coleta de Dados , Humanos , Doenças Raras , Inquéritos e QuestionáriosRESUMO
Background: There is currently no standard definition of medical affairs, despite its increasing importance to the pharmaceutical industry. The evolution of medical affairs necessitated the development of a standardised definition to guide policy and practice to ensure that patients' interests remain central amid shifts that have, in the past, created fertile ground for ethical violations. Objectives: The aim of this study was to use an empirical method to observe a consensus of expert opinion on the definition of medical affairs to guide policy and practice within this function. Methods: In total, 11 medical affairs pharmaceutical physicians (MAPPs) completed a qualitative online survey to identify a list of key items to define medical affairs using the Jandhyala method for generating a consensus of expert opinion. Responses were coded and scored, and aggregated responses were presented to participants in a consensus round. Participants rated their agreement with each item on a 5-point Likert scale from strongly agree to strongly disagree. Indicators that reached a consensus index of >50% (CI > = 0.51) were retained. Items were categorised per previously defined medical affairs functions to determine the scope of the definition. A comparative content analysis using a previous definition identified in the literature was conducted to determine the utility of the definition generated here. Results: In total, 11 MAPPs generated 15 unique items to define medical affairs. Item awareness indices ranged from 0.24 ('communication/education') to 1.00 ('design/strategy'). All items had a CI of more than 0.5 and were included in the final definition. All items could be categorised per previously defined medical affairs functions. Comparative content analysis showed that our definition varied in four ways: the designation of medical affairs as a medical specialty (and its primary aim, therefore, is to protect patients), the leadership of medical affairs in medicine adoption, the generation of real-world evidence and the specification of distinct stakeholders who benefit from medical affairs. Conclusion: A standard definition of medical affairs that incorporates the key principles of medical affairs as a medical specialty that leads medicine adoption and generates real-world evidence for specific stakeholders may protect and further the interests of patients by governing practice and policy.