Compliance with legal requirement to report clinical trial results on ClinicalTrials.gov: a cohort study.

BACKGROUND: Failure to report the results of a clinical trial can distort the evidence base for clinical practice, breaches researchers' ethical obligations to participants, and represents an important source of research waste. The Food and Drug Administration Amendments Act (FDAAA) of 2007 now requires sponsors of applicable trials to report their results directly onto ClinicalTrials.gov within 1 year of completion. The first trials covered by the Final Rule of this act became due to report results in January, 2018. In this cohort study, we set out to assess compliance. METHODS: We downloaded data for all registered trials on ClinicalTrials.gov each month from March, 2018, to September, 2019. All cross-sectional analyses in this manuscript were performed on data extracted from ClinicalTrials.gov on Sept 16, 2019; monthly trends analysis used archived data closest to the 15th day of each month from March, 2018, to September, 2019. Our study cohort included all applicable trials due to report results under FDAAA. We excluded all non-applicable trials, those not yet due to report, and those given a certificate allowing for delayed reporting. A trial was considered reported if results had been submitted and were either publicly available, or undergoing quality control review at ClinicalTrials.gov. A trial was considered compliant if these results were submitted within 1 year of the primary completion date, as required by the legislation. We described compliance with the FDAAA 2007 Final Rule, assessed trial characteristics associated with results reporting using logistic regression models, described sponsor-level reporting, examined trends in reporting, and described time-to-report using the Kaplan-Meier method. FINDINGS: 4209 trials were due to report results; 1722 (40·9%; 95% CI 39·4-42·2) did so within the 1-year deadline. 2686 (63·8%; 62·4-65·3) trials had results submitted at any time. Compliance has not improved since July, 2018. Industry sponsors were significantly more likely to be compliant than non-industry, non-US Government sponsors (odds ratio [OR] 3·08 [95% CI 2·52-3·77]), and sponsors running large numbers of trials were significantly more likely to be compliant than smaller sponsors (OR 11·84 [9·36-14·99]). The median delay from primary completion date to submission date was 424 days (95% CI 412-435), 59 days higher than the legal reporting requirement of 1 year. INTERPRETATION: Compliance with the FDAAA 2007 is poor, and not improving. To our knowledge, this is the first study to fully assess compliance with the Final Rule of the FDAAA 2007. Poor compliance is likely to reflect lack of enforcement by regulators. Effective enforcement and action from sponsors is needed; until then, open public audit of compliance for each individual sponsor may help. We will maintain updated compliance data for each individual sponsor and trial at fdaaa.trialstracker.net. FUNDING: Laura and John Arnold Foundation.

Truth in research labelling.

This report describes the background and context of a currently circulating petition to the US Congress that seeks amendment of Section 801 of the Public Health Services Act (42 U.S.C. 282) to close a loophole in existing law which makes possible post hoc adjustment of randomised controlled trial (RCT) results reported to the Food and Drug Administration that differ from those reported to ClinicalTrials.gov and to medical journals. The report describes the petition's rationale, underlying assumptions, and support for its proposed remedy in deontological, consequentialist, and casuist philosophical ethics theories. It addresses the several reservations of the World Association of Medical Editors (WAME) with citations of evidence for the petition's assertions. The report suggests that some medical journals are not unknowing victims but rather complicit enablers of the post hoc adjusted RCT results that they publish. Its closing remarks dwell on the negative impact that embrace of a neoliberal, anti-regulatory philosophy of government will likely have on any regulatory reform to promote the integrity of biomedical science and the future of evidence-based medicine.

Pharmacovigilance of Regenerative Medicine Under the Amended Pharmaceutical Affairs Act in Japan.

Two Japanese regulatory agencies, the Ministry of Health, Labour and Welfare and the Pharmaceuticals and Medical Devices Agency announced the implementation of a new review system called 'Conditional Approval,' specifically for the emerging field of regenerative medicine, in an amendment to the Pharmaceutical Affairs Act in 2014. Regenerative medicine was regulated in the category of 'Medical Devices' prior to the amendment and was not covered by the Relief Service, a system that provides financial aid to people who have experienced an adverse drug reaction and developed serious side effects as a result. Through the amendment, regenerative medicine is defined as a new category and is covered by the Relief Service under the amended Pharmaceutical Affairs Act, called the 'Act on Securing Quality, Efficacy and Safety of Pharmaceuticals, Medical Devices, Regenerative and Cellular Therapy Products, Gene Therapy Products, and Cosmetics' (PMD Act). This amendment allows the use of Relief Service data for pharmacovigilance activities, making the Relief Service the third adverse drug reaction reporting route in addition to the existing reporting routes from marketing authorization holders and healthcare providers. For optimum incorporation and use of this Relief Service data, earlier access should be allowed even before the reports from the Pharmaceuticals and Medical Devices Agency to the Ministry of Health, Labour and Welfare are finalized, which is mandatory under the current PMD Act.

Ethical perspectives and ramifications of the Paolo Macchiarini case.

The Paolo Macchiarini case has several ethical ramifications. Professor Macchiarini, formerly of the Karolinska Institutet (KI), became famous for the tracheal surgeries he conducted between 2008 and 2014. His rapid rise to fame was followed by an almost equally rapid fall from grace as official reports, articles in newspapers and television programmes revealed several aspects related to misconduct in his curriculum vitae, professional practices and publishing-related activity. Formal misconduct reports issued by four KI co-workers in late 2014, then again in 2016, coupled with social scandals, including the tricking of a famous US television newscaster into a false marriage, a previous arrest in Italy for apparent bribery, and acute narcissism, all tainted Macchiarini's legend. In the short space of just two years, Macchiarini was no longer remembered for the revolutionary changes he had claimed to have brought about in stem cell research and regenerative medicine. Instead, at least seven dead patients later, Macchiarini faces potential aggravated manslaughter charges and an uphill battle to save his published research, now shrouded in scandal and scientific doubt, from being retracted and scratched out from the list of verified medical science. This paper examines some of the possible ethical ramifications of the Macchiarini case.

Reflexões sobre práticas psi-jurídicas na triagem da Defensoria Pública Paulista / Reflections on psycho-legal practices in the triage of the Public Defender's Office of São Paulo / Reflexiones acerca de las prácticas psi-jurídicas en la selección de la Defensoría Pública Paulista

Neste artigo, apresentamos alguns desdobramentos da pesquisa de doutorado na qual estudamos encontros psi-jurídicos na Defensoria Pública do Estado de São Paulo, tomando a experiência dos Centros de Atendimento Multidisciplinar (CAMs) como objeto. Por meio da metodologia qualitativa da pesquisa-intervenção que contou com a elaboração de diários e de narrativas, empreendemos o acompanhamento das práticas profissionais que envolviam o trabalho conjunto de defensores, assistentes sociais e psicólogos na Defensoria Pública, entre 2011 e 2013. Aqui, privilegiamos mostrar a triagem, espaço no qual é feito o primeiro atendimento às pessoas que buscam assistência jurídica, que nos possibilitou nos aproximar da gestão dos pedidos e de como eles se transformam em demandas jurídicas, não jurídicas e psicossociais. Para tanto, utilizamos informações das fichas dos encaminhamentos feitos a um CAM nos anos de 2010 e 2011, com situações vivenciadas no percurso da pesquisa. Os operadores conceituais do estudo se apoiam no pensamento foucaultiano e na Análise Institucional francesa. A triagem mostrou que se privilegia a partilha tradicional entre os saberes, tendendo-se a (re)produzir uma assistência jurídica "desintegrada" e disciplinarizada, oferecendo-se um modo familialista de resposta às problemáticas apresentadas pela população. No entanto as questões de saúde mental emergem como algo que escapa às divisões, produzindo desvios no processo de trabalho. Acreditamos que esses modos de saber-fazer engendram uma assistência jurídica que tende à atenção integral, constituindo-se numa experiência de pensar-saber-fazer entre profissões que não se submete aos protocolos e divisões já instituídos.

In this article, we presented some developments of the doctoral research in which were studied psycho-legal encounters at the Defensoria Pública do Estado de São Paulo (Public Defender's Office of the State of São Paulo), taking the experience of the Centros de Atendimento Multidisciplinar (Multidisciplinary Assistance Centers­CAMs, acronym in Portuguese) as subject. Through a qualitative intervention-research methodology based on diaries and narrative construction, we have monitored professional practices involving the joint work of defenders, social workers and psychologists at the Public Defender's Office, between 2011 and 2013. Here, we decided to focus on the triage, space where the first assistance to people who look for legal help is performed, which allowed us to get in contact with the management of requests and the way they become legal, non-legal and psycho-social demands. In order to do that, we used information from referral forms sent to a CAM in the years 2010 and 2011, along with situations experienced in the course of this research. The theoretical references of this study are Foucault's thought and French Institutional Analysis. The triage showed that a traditional division between knowledges is utilized, which tends to (re)produce an "unintegrated" and disciplined legal assistance, providing a familialist mode of response to the problems presented by the population. However, mental health issues emerge as something that escapes divisions, producing shifts in the work process. We believe these ways of knowing-how-to-do generate a legal assistance that tends to be more oriented to comprehensive care, constituting anexperience of thinking-knowing-doing between professions that does not submit to protocols and divisions already established.

En este artículo, presentamos algunas evoluciones de la investigación de Doctorado de en la que estudiamos los encuentros psi-jurídicos en la Defensoría Pública del Estado de São Paulo, teniendo la experiencia de los Centros de Atendimiento Multidisciplinar (CAMs) como objeto. Por intermedio de la metodología cualitativa de la investigación-intervención que incluyó la elaboración de diarios y narrativas, se llevó a cabo el estudio de prácticas profesionales en la Defensoría Pública, entre 2011 y 2013. Aquí, centramos en la que muestra el espacio de selección, en el que se hace la primera atención a las personas que buscan asistencia jurídica, lo que hizo posible acercarse a la gestión de pedidos y respecto a cómo ellos se convierten en exigencias jurídicas, no jurídicas y psicosociales. Para eso, utilizamos informaciones de los registros de derivaciones al CAM, locus de la investigación en 2010 y 2011 y del informe elaborado por la Asesoría Técnica Psicosocial (ATP), cuyos datos presentan el trabajo de equipos de CAM en 2011, además de las situaciones vividas en el camino de la investigación. Los operadores conceptuales del estudio se basan en el pensamiento de Foucault y en el Análisis Institucional francesa. La selección mostró favorecer la división tradicional entre los saberes, tendiendo a (re)producir una asistencia jurídica "desintegrada", disciplinarizada y despolitizada, que ofrece una forma familialista de la respuesta a los problemas presentados por la población. Sin embargo, las cuestiones de salud mental emergen como algo que escapa a las divisiones, produciendo desvíos en el proceso de trabajo. Creemos que estos modos de conocimientos engendran una asistencia jurídica que tiende a la atención integral, constituyéndose en una experiencia de pensar-saber-hacer entre profesiones que no está sujeta a los protocolos y las divisiones ya establecidos.

Formulation and communication of evaluative forensic science expert opinion-A GHEP-ISFG contribution to the establishment of standards.

Communicating and interpreting genetic evidence in the administration of justice is currently a matter of great concern, due to the theoretical and technical complexity of the evaluative reporting and large difference in expertise between forensic experts and law professionals. A large number of initiatives have been taken trying to bridge this gap, contributing to the education of both parties. Results however have not been very encouraging, as most of these initiatives try to cope globally with the problem, addressing simultaneously theoretical and technical approaches which are in a quite heterogeneous state of development and validation. In consequence, the extension and complexity of the resulting documents disheartens their study by professionals (both jurists and geneticists) and makes a consensus very hard to reach even among the genetic experts' community. Here we propose a 'back-to-basics', example-driven approach, in which a model report for the two most common situations faced by forensic laboratories is presented. We do hope that this strategy will provide a solid basis for a stepwise generalisation.

A multistage crucible of revision and approval shapes IPCC policymaker summaries.

Intergovernmental Panel on Climate Change (IPCC) member governments approve each report's summary for policymakers (SPM) by consensus, discussing and agreeing on each sentence in a plenary session with scientist authors. A defining feature of IPCC assessment, the governmental approval process builds joint ownership of current knowledge by scientists and governments. The resulting SPM revisions have been extensively discussed in anecdotes, interviews, and perspectives, but they have not been comprehensively analyzed. We provide an in-depth evaluation of IPCC SPM revisions, establishing an evidential basis for understanding their nature. Revisions associated with governmental review and approval generally expand SPMs, with SPM text growing by 17 to 53% across recent assessment reports. Cases of high political sensitivity and failure to reach consensus are notable exceptions, resulting in SPM contractions. In contrast to recent claims, we find that IPCC SPMs are as readable, for multiple metrics of reading ease, as other professionally edited assessment summaries. Across reading-ease metrics, some SPMs become more readable through governmental review and approval, whereas others do not. In an SPM examined through the entire revision process, most revisions associated with governmental review and approval occurred before the start of the government-approval plenary session. These author revisions emphasize clarity, scientific rigor, and explanation. In contrast, the subsequent plenary revisions place greater emphasis especially on policy relevance, comprehensiveness of examples, and nuances of expert judgment. Overall, the value added by the IPCC process emerges in a multistage crucible of revision and approval, as individuals together navigate complex science-policy terrain.

Few comply with clinical trials reporting law.

The Food and Drug Administration Amendments Act requires researchers to submit clinical trial results to ClinicalTrials.gov within a year of completion. However, a new study indicates that only 13.4% of trials comply.