RESUMO
The cost of drug discovery and development is driven primarily by failure1, with only about 10% of clinical programmes eventually receiving approval2-4. We previously estimated that human genetic evidence doubles the success rate from clinical development to approval5. In this study we leverage the growth in genetic evidence over the past decade to better understand the characteristics that distinguish clinical success and failure. We estimate the probability of success for drug mechanisms with genetic support is 2.6 times greater than those without. This relative success varies among therapy areas and development phases, and improves with increasing confidence in the causal gene, but is largely unaffected by genetic effect size, minor allele frequency or year of discovery. These results indicate we are far from reaching peak genetic insights to aid the discovery of targets for more effective drugs.
Assuntos
Ensaios Clínicos como Assunto , Aprovação de Drogas , Descoberta de Drogas , Resultado do Tratamento , Humanos , Alelos , Ensaios Clínicos como Assunto/economia , Ensaios Clínicos como Assunto/estatística & dados numéricos , Aprovação de Drogas/economia , Descoberta de Drogas/economia , Descoberta de Drogas/métodos , Descoberta de Drogas/estatística & dados numéricos , Descoberta de Drogas/tendências , Frequência do Gene , Predisposição Genética para Doença , Terapia de Alvo Molecular , Probabilidade , Fatores de Tempo , Falha de TratamentoRESUMO
Despite major advances in HIV-1 therapeutics and prevention strategies, the development of a safe and effective prophylactic HIV-1 vaccine will likely be critical for ending the global HIV-1 epidemic. Yet only four HIV-1 vaccine concepts have been tested for clinical efficacy over the past 30 years. In this Commentary, we describe key hurdles facing the HIV-1 vaccine development field and outline strategies to accelerate efficacy evaluation of novel HIV-1 vaccine candidates.
Assuntos
Vacinas contra a AIDS/uso terapêutico , Ensaios Clínicos como Assunto , HIV-1/fisiologia , Pesquisa Biomédica/economia , Ensaios Clínicos como Assunto/economia , Feminino , Infecções por HIV/prevenção & controle , Infecções por HIV/virologia , HIV-1/genética , Humanos , MasculinoRESUMO
Patients from historically under-represented racial and ethnic groups are enrolled in cancer clinical trials at disproportionately low rates in the USA1-3. As these patients often have limited English proficiency4-7, we hypothesized that one barrier to their inclusion is the cost to investigators of translating consent documents. To test this hypothesis, we evaluated more than 12,000 consent events at a large cancer centre and assessed whether patients requiring translated consent documents would sign consent documents less frequently in studies lacking industry sponsorship (for which the principal investigator pays the translation costs) than for industry-sponsored studies (for which the translation costs are covered by the sponsor). Here we show that the proportion of consent events for patients with limited English proficiency in studies not sponsored by industry was approximately half of that seen in industry-sponsored studies. We also show that among those signing consent documents, the proportion of consent documents translated into the patient's primary language in studies without industry sponsorship was approximately half of that seen in industry-sponsored studies. The results suggest that the cost of consent document translation in trials not sponsored by industry could be a potentially modifiable barrier to the inclusion of patients with limited English proficiency.
Assuntos
Ensaios Clínicos como Assunto , Barreiras de Comunicação , Termos de Consentimento , Indústria Farmacêutica , Pesquisadores , Traduções , Humanos , Termos de Consentimento/economia , Tradução , Ensaios Clínicos como Assunto/economia , Indústria Farmacêutica/economia , Pesquisadores/economiaRESUMO
BACKGROUND: The dissemination of clinical trial results is an important scientific and ethical endeavour. This survey of completed interventional studies in a French academic center describes their reporting status. METHODS: We explored all interventional studies sponsored by Rennes University Hospital identified on the French Open Science Monitor which tracks trials registered on EUCTR or clinicaltrials.gov, and provides an automatic assessment of the reporting of results. For each study, we ascertained the actual reporting of results using systematic searches on the hospital internal database, bibliographic databases (Google Scholar, PubMed), and by contacting all principal investigators (PIs). We describe several features (including total budget and numbers of trial participants) of the studies that did not report any results. RESULTS: The French Open Science Monitor identified 93 interventional studies, among which 10 (11%) reported results. In contrast, our survey identified 36 studies (39%) reporting primary analysis results and an additional 18 (19%) reporting results for secondary analyses (without results for their primary analysis). The overall budget for studies that did not report any results was estimated to be 5,051,253 for a total of 6,735 trial participants. The most frequent reasons for the absence of results reported by PIs were lack of time for 18 (42%), and logistic difficulties (e.g. delay in obtaining results or another blocking factor) for 12 (28%). An association was found between non-publication and negative results (adjusted Odds Ratio = 4.70, 95% Confidence Interval [1.67;14.11]). CONCLUSIONS: Even allowing for the fact that automatic searches underestimate the number of studies with published results, the level of reporting was disappointingly low. This amounts to a waste of trial participants' implication and money. Corrective actions are needed. TRIAL REGISTRATION: https://osf.io/q5hcs.
Assuntos
Ensaios Clínicos como Assunto , Humanos , Centros Médicos Acadêmicos/estatística & dados numéricos , Ensaios Clínicos como Assunto/estatística & dados numéricos , Ensaios Clínicos como Assunto/métodos , Ensaios Clínicos como Assunto/economia , França , Projetos de Pesquisa , Inquéritos e Questionários , Estudos TransversaisRESUMO
BACKGROUND: There is increasing interest in the capacity of adaptive designs to improve the efficiency of clinical trials. However, relatively little work has investigated how economic considerations - including the costs of the trial - might inform the design and conduct of adaptive clinical trials. METHODS: We apply a recently published Bayesian model of a value-based sequential clinical trial to data from the 'Hydroxychloroquine Effectiveness in Reducing symptoms of hand Osteoarthritis' (HERO) trial. Using parameters estimated from the trial data, including the cost of running the trial, and using multiple imputation to estimate the accumulating cost-effectiveness signal in the presence of missing data, we assess when the trial would have stopped had the value-based model been used. We used re-sampling methods to compare the design's operating characteristics with those of a conventional fixed length design. RESULTS: In contrast to the findings of the only other published retrospective application of this model, the equivocal nature of the cost-effectiveness signal from the HERO trial means that the design would have stopped the trial close to, or at, its maximum planned sample size, with limited additional value delivered via savings in research expenditure. CONCLUSION: Evidence from the two retrospective applications of this design suggests that, when the cost-effectiveness signal in a clinical trial is unambiguous, the Bayesian value-adaptive design can stop the trial before it reaches its maximum sample size, potentially saving research costs when compared with the alternative fixed sample size design. However, when the cost-effectiveness signal is equivocal, the design is expected to run to, or close to, the maximum sample size and deliver limited savings in research costs.
Assuntos
Teorema de Bayes , Análise Custo-Benefício , Osteoartrite , Projetos de Pesquisa , Humanos , Análise Custo-Benefício/métodos , Análise Custo-Benefício/estatística & dados numéricos , Osteoartrite/economia , Osteoartrite/tratamento farmacológico , Osteoartrite/terapia , Hidroxicloroquina/uso terapêutico , Hidroxicloroquina/economia , Ensaios Clínicos como Assunto/métodos , Ensaios Clínicos como Assunto/economia , Ensaios Clínicos como Assunto/estatística & dados numéricos , Tamanho da AmostraRESUMO
Clinical research should conform to high standards of ethical and scientific integrity, given that human lives are at stake. However, economic incentives can generate conflicts of interest for investigators, who may be inclined to withhold unfavorable results or even tamper with data in order to achieve desired outcomes. To shed light on the integrity of clinical trial results, this paper systematically analyzes the distribution of P values of primary outcomes for phase II and phase III drug trials reported to the ClinicalTrials.gov registry. First, we detect no bunching of results just above the classical 5% threshold for statistical significance. Second, a density-discontinuity test reveals an upward jump at the 5% threshold for phase III results by small industry sponsors. Third, we document a larger fraction of significant results in phase III compared to phase II. Linking trials across phases, we find that early favorable results increase the likelihood of continuing into the next phase. Once we take into account this selective continuation, we can explain almost completely the excess of significant results in phase III for trials conducted by large industry sponsors. For small industry sponsors, instead, part of the excess remains unexplained.
Assuntos
Ensaios Clínicos como Assunto/economia , Ensaios Clínicos como Assunto/normas , Relatório de Pesquisa/normas , Pesquisa Biomédica/economia , Ensaios Clínicos como Assunto/estatística & dados numéricos , Desenvolvimento de Medicamentos/economia , Desenvolvimento de Medicamentos/organização & administração , Indústria Farmacêutica/economia , Humanos , Sistema de Registros , Apoio à Pesquisa como AssuntoRESUMO
Reimbursement of participants in clinical trials is extensively debated. Guidance recommends that compensation should reflect time, inconvenience and reimbursement of expenses. This study describes how participants spend their reimbursement and perceptions of appropriate reimbursement amounts. This was a sub-study of the evidence for contraceptive options and HIV outcomes (ECHO) trial. Participants were from two sites in KwaZulu-Natal, South Africa. A mixed methods approach was used. 500 participants completed a questionnaire, and 32 participated in one of four focus group discussions (FGD). The majority (81%) used reimbursement for transport to the research site, followed by toiletry purchases (64%). Many described how reimbursement supplemented income, used to cover basic living costs. Some used money to buy luxury items and takeaway foods. The ideal reimbursement amount per visit ranged: ZAR150-ZAR340 (US$10-24). Reimbursement spending and perceptions are in line with local guidance. Reimbursement should consider risk minimization together with ensuring informed, voluntary decision making.
Assuntos
Ensaios Clínicos como Assunto , Infecções por HIV , População Negra , Ensaios Clínicos como Assunto/economia , Anticoncepcionais , Infecções por HIV/prevenção & controle , Humanos , Renda , África do SulAssuntos
Ensaios Clínicos como Assunto/métodos , Ensaios Clínicos como Assunto/organização & administração , Seleção de Pacientes , Projetos de Pesquisa , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Ensaios Clínicos como Assunto/economia , Feminino , Disparidades em Assistência à Saúde , Humanos , Preconceito/prevenção & controle , Grupos Raciais , Tamanho da Amostra , Estados Unidos , United States Food and Drug Administration/legislação & jurisprudênciaAssuntos
Vacinas contra COVID-19/provisão & distribuição , COVID-19/prevenção & controle , Doença , Vacinologia/tendências , COVID-19/imunologia , Vacinas contra COVID-19/efeitos adversos , Vacinas contra COVID-19/economia , Vacinas contra COVID-19/imunologia , Ensaios Clínicos como Assunto/economia , Humanos , SARS-CoV-2/imunologia , Fatores de Tempo , Vacinologia/economiaAssuntos
Vacinas contra COVID-19 , Vacinas Sintéticas , Animais , Anticorpos Neutralizantes/sangue , Anticorpos Neutralizantes/imunologia , COVID-19/epidemiologia , COVID-19/imunologia , COVID-19/virologia , Vacinas contra COVID-19/efeitos adversos , Vacinas contra COVID-19/economia , Vacinas contra COVID-19/imunologia , Vacinas contra COVID-19/provisão & distribuição , Ensaios Clínicos como Assunto/economia , Modelos Animais de Doenças , Humanos , Camundongos , Motivação , Patentes como Assunto/legislação & jurisprudência , SARS-CoV-2/imunologia , Tailândia/epidemiologia , Fatores de Tempo , Vacinas Sintéticas/efeitos adversos , Vacinas Sintéticas/economia , Vacinas Sintéticas/imunologia , Vacinas Sintéticas/provisão & distribuição , Vacinas de mRNAAssuntos
Pesquisa Biomédica/economia , Pesquisa Biomédica/legislação & jurisprudência , Orçamentos/legislação & jurisprudência , COVID-19 , Cooperação Internacional/legislação & jurisprudência , Pesquisadores , Apoio à Pesquisa como Assunto/legislação & jurisprudência , COVID-19/economia , COVID-19/epidemiologia , Ensaios Clínicos como Assunto/economia , Humanos , Pesquisadores/economia , Pesquisadores/psicologia , Incerteza , Reino Unido , Universidades/economiaRESUMO
The global burden of cancer is estimated to be more than 20 million cases by 2030, the majority occurring in low- and middle- income countries (LMICs). LMICs account for 64% of global cancer deaths and 80% of disability-adjusted-life-years lost. Despite this, only 5% of the global cancer resources are spent in LMICs causing a high mortality-to-income ratio. Despite the burgeoning number of clinical trials in the HICs, there are several reasons to conduct clinical trials in LMICs. In this commentary, we discuss the problem of access to clinical trials in LMICs using India as a case study.
Assuntos
Ensaios Clínicos como Assunto/economia , Ensaios Clínicos como Assunto/estatística & dados numéricos , Efeitos Psicossociais da Doença , Neoplasias/terapia , Sistema de Registros/estatística & dados numéricos , Países em Desenvolvimento , Detecção Precoce de Câncer/economia , Detecção Precoce de Câncer/métodos , Humanos , Índia , Neoplasias/diagnóstico , Neoplasias/economiaAssuntos
Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/prevenção & controle , Pandemias/prevenção & controle , Pneumonia Viral/epidemiologia , Pneumonia Viral/prevenção & controle , Incerteza , Vacinas Virais/provisão & distribuição , Vacinas Virais/normas , Adenoviridae/genética , Administração Intranasal , Animais , Biotecnologia , COVID-19 , Vacinas contra COVID-19 , Ensaios Clínicos como Assunto/economia , Ensaios Clínicos como Assunto/organização & administração , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/virologia , Modelos Animais de Doenças , Indústria Farmacêutica , Humanos , Imunidade nas Mucosas/imunologia , Vacinas contra Influenza/imunologia , Camundongos , Pneumonia Viral/imunologia , Pneumonia Viral/virologia , Resultado do Tratamento , Vacinas Virais/administração & dosagem , Vacinas Virais/imunologiaAssuntos
Infecções por Coronavirus/prevenção & controle , Alocação de Recursos para a Atenção à Saúde , Recursos em Saúde , Pandemias/prevenção & controle , Pneumonia Viral/prevenção & controle , Fatores Socioeconômicos , Vacinas Virais/economia , Vacinas Virais/provisão & distribuição , COVID-19 , Vacinas contra COVID-19 , Criança , Ensaios Clínicos como Assunto/economia , Infecções por Coronavirus/economia , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/imunologia , Países Desenvolvidos/economia , Indústria Farmacêutica/economia , Alocação de Recursos para a Atenção à Saúde/economia , Alocação de Recursos para a Atenção à Saúde/organização & administração , Recursos em Saúde/economia , Recursos em Saúde/organização & administração , Colecionismo/prevenção & controle , Humanos , Imunização Secundária , Cooperação Internacional , Investimentos em Saúde , Pandemias/economia , Pneumonia Viral/economia , Pneumonia Viral/epidemiologia , Pneumonia Viral/imunologia , Estoque Estratégico , Fatores de Tempo , Nicotiana/genética , Nicotiana/metabolismo , Nicotiana/virologia , Vacinas de Subunidades Antigênicas/provisão & distribuição , Vacinas Sintéticas/provisão & distribuição , Vacinas Virais/efeitos adversos , Organização Mundial da SaúdeRESUMO
The proposed triple aim of health care-enhanced patient experience, improved population health, and reduced per capita costs-can be applied to clinical research. A triple aim for clinical research would (1) improve the individual research participant's experience; (2) promote the health of populations; and (3) reduce per capita costs of clinical research. Such an approach is possible by designing trials around the needs of participants rather than sites, embracing digital measures of health, and advancing decentralized studies. Recent studies, including those evaluating therapies for COVID-19, have demonstrated the value of such an approach. Accelerating the adoption of these methods can help fulfill this new triple aim of clinical research.
Assuntos
Ensaios Clínicos como Assunto/métodos , Objetivos , Saúde da População , Sujeitos da Pesquisa , Apoio à Pesquisa como Assunto , Pesquisa Biomédica/economia , Pesquisa Biomédica/métodos , Pesquisa Biomédica/organização & administração , Ensaios Clínicos como Assunto/economia , Ensaios Clínicos como Assunto/organização & administração , Custos e Análise de Custo , Promoção da Saúde , Humanos , Satisfação do Paciente , TelemedicinaRESUMO
Trials are in development and underway to examine potential interventions for treatment and prophylaxis of coronavirus disease 2019 (COVID-19). How should we think about offering payment to participants in these trials? Payment for research participation is ethically contentious even under ideal circumstances. Here, we review 3 functions of research payment-reimbursement, compensation, and incentive-and identify heightened and novel ethical concerns in the context of a global pandemic. We argue that COVID-19 trial participants should usually be offered reimbursement for research-related expenses, and compensation for their time and effort, as for other types of research under usual circumstances. Given increased risk of undue influence against pandemic background conditions, incentive payment should be avoided unless essential to recruitment and retention in important trials whose social value outweighs this risk. Where essential, however, incentives can be ethically permissible, so long as reasonable efforts are made to minimize the possibility of undue influence.
Assuntos
Ensaios Clínicos como Assunto/economia , Infecções por Coronavirus/terapia , Voluntários Saudáveis , Pneumonia Viral/terapia , COVID-19 , Ensaios Clínicos como Assunto/ética , Compensação e Reparação/ética , Infecções por Coronavirus/prevenção & controle , Humanos , Motivação/ética , Pandemias/prevenção & controle , Pneumonia Viral/prevenção & controle , Pesquisa/economiaRESUMO
Christian Lienhardt and co-authors discuss the conclusions of the PLOS Medicine Collection on advances in clinical trial design for development of new tuberculosis treatments.
Assuntos
Antituberculosos/uso terapêutico , Ensaios Clínicos como Assunto/métodos , Tuberculose/tratamento farmacológico , Antituberculosos/farmacologia , Ensaios Clínicos como Assunto/economia , Ensaios Clínicos Fase II como Assunto/economia , Ensaios Clínicos Fase II como Assunto/métodos , Ensaios Clínicos Fase III como Assunto/economia , Ensaios Clínicos Fase III como Assunto/métodos , Desenvolvimento de Medicamentos , Avaliação Pré-Clínica de Medicamentos , Humanos , Adesão à Medicação , Fatores de Tempo , Pesquisa Translacional Biomédica , Populações VulneráveisAssuntos
COVID-19/prevenção & controle , Prática de Saúde Pública , Desenvolvimento de Vacinas , Eficácia de Vacinas , Vacinas/provisão & distribuição , Vacinas contra COVID-19/provisão & distribuição , Ensaios Clínicos como Assunto/economia , Planejamento em Desastres , Aprovação de Drogas , Vetores Genéticos , Humanos , Imunogenicidade da Vacina , Fatores de Tempo , Desenvolvimento de Vacinas/economia , Desenvolvimento de Vacinas/métodos , Vacinas de mRNARESUMO
Members of racial and ethnic minority groups make up nearly 50% of US patients with end-stage kidney disease and face a disproportionate burden of socioeconomic challenges (ie, low income, job insecurity, low educational attainment, housing instability, and communication challenges) compared with non-Hispanic whites. Patients with end-stage kidney disease who face social challenges often have poor patient-centered and clinical outcomes. These challenges may have a negative impact on quality-of-care performance measures for dialysis facilities caring for primarily minority and low-income patients. One path toward improving outcomes for this group is to develop culturally tailored interventions that provide individualized support, potentially improving patient-centered, clinical, and health system outcomes by addressing social challenges. One such approach is using community-based culturally and linguistically concordant patient navigators, who can serve as a bridge between the patient and the health care system. Evidence points to the effectiveness of patient navigators in the provision of cancer care and, to a lesser extent, caring for people with chronic kidney disease and those who have undergone kidney transplantation. However, little is known about the effectiveness of patient navigators in the care of patients with kidney failure receiving dialysis, who experience a number of remediable social challenges.
Assuntos
Disparidades em Assistência à Saúde , Falência Renal Crônica/terapia , Navegação de Pacientes/métodos , Diálise Renal/métodos , Fatores Socioeconômicos , Ensaios Clínicos como Assunto/economia , Ensaios Clínicos como Assunto/métodos , Disparidades em Assistência à Saúde/economia , Humanos , Falência Renal Crônica/economia , Navegação de Pacientes/economia , Diálise Renal/economiaRESUMO
The sales of dietary supplements continue to increase year after year. Despite their use by a large percentage of Americans, there is little evidence for the vast majority of products regarding their safety or efficacy. National Center for Complementary and Integrative Health supports a broad range of research on dietary supplements, including clinical trials. Our experience with these trials has shaped our current policies and priorities for clinical research. This perspective outlines those policies and priorities that are shaping our investments going forward. SIGNIFICANCE STATEMENT: The sales of dietary supplements continue to increase year after year. Despite their use by a large percentage of Americans, there is little evidence for the vast majority of products regarding their safety or efficacy. National Center for Complementary and Integrative Health supports a broad range of research on dietary supplements, including clinical trials. Our experience with these trials has shaped our current policies and priorities for clinical research. This perspective outlines those policies and priorities that are shaping our investments going forward.