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1.
Mayo Clin Proc ; 95(12): 2699-2703, 2020 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-33276841

RESUMEN

Approval by the US Food and Drug Administration (FDA) of a drug for a given indication is thought to reassure clinicians, other health care providers, and patients that substantial evidence of effectiveness exists for specific indicated populations (patients and diseases). This study examines whether FDA approval of certain antibiotics should be so reassuring for all patient populations identified in the FDA-approved labels. Specifically, this study compared patient populations covered by FDA-approved labels for 21 novel antibiotics approved between 1999 and 2018 to the patient exclusion and inclusion criteria of pivotal trials that supported those approvals. We found that every FDA-approved label for these antibiotics included at least one identifiable patient population that was explicitly excluded from enrolling in the supporting pivotal trials. Two antibiotics, bedaquiline and ceftazidime-avibactam, were approved for use in populations that were fully excluded from enrolling in registration trials.

5.
BMJ ; 371: m4037, 2020 10 21.
Artículo en Inglés | MEDLINE | ID: mdl-33087398
6.
BMJ ; 370: m3563, 2020 09 17.
Artículo en Inglés | MEDLINE | ID: mdl-32943427
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BMJ Evid Based Med ; 25(6): 213-219, 2020 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-32184277

RESUMEN

PURPOSE: Trustworthy reporting of quadrivalent human papillomavirus (HPV) vaccine trials is the foundation for assessing the vaccine's risks and benefits. However, several pivotal trial publications incompletely reported important methodological details and inaccurately described the formulation that the control arms received. Under the Restoring Invisible and Abandoned Trials initiative (RIAT), we aim to restore the public record regarding the content and rationale of the controls used in the trials. METHODS: We assembled a cohort (five randomised controlled trials) described as placebo-controlled using clinical study reports (CSRs) obtained from the European Medicines Agency. We extracted the content and rationale for the choice of control used in each trial across six data sources: trial publications, register records, CSR synopses, CSR main bodies, protocols and informed consent forms. RESULTS: Across data sources, the control was inconsistently reported as 'placebo'-containing aluminium adjuvant (sometimes with dose information). Amorphous aluminium hydroxyphosphate sulfate (AAHS) was not mentioned in any trial registry entry, but was mentioned in all publications and CSRs. In three of five trials, consent forms described the control as an 'inactive' substance. No rationale for the selection of the control was reported in any trial publication, register, consent form, CSR synopsis or protocol. Three trials reported the rationale for choice of control in CSRs: to preserve blinding and assess the safety of HPV virus-like particles as the 'safety profile of (AAHS) is well characterised'. CONCLUSIONS: The stated rationale of using AAHS control-to characterise the safety of the HPV virus-like particles-lacks clinical relevance. A non-placebo control may have obscured an accurate assessment of safety and the participant consent process of some trials raises ethical concerns. TRIAL REGISTRATION NUMBERS: NCT00092482, NCT00092521, NCT00092534, NCT00090220, NCT00090285.

12.
BMJ ; 368: m734, 2020 Feb 26.
Artículo en Inglés | MEDLINE | ID: mdl-32102785
13.
BMJ Evid Based Med ; 2020 Feb 26.
Artículo en Inglés | MEDLINE | ID: mdl-32102872

RESUMEN

Globally, drug regulators have approved statins for the prevention of cardiovascular disease (CVD), although their use in primary prevention has been controversial. A highly publicised debate has ensued over whether the benefits outweigh the harms. Drug regulators, which are legally required to make independent judgements on drug approvals, have remained silent during the debate. Our aim was to navigate the decision-making processes of European drug regulators and ultimately request the data upon which statins were approved. Our findings revealed a system of fragmented regulation in which many countries licensed statins but did not analyse the data themselves. There is no easily accessible archive containing information about the licensing approval of statins or a central location for holding the trial data. This is an unsustainable model and serves neither the general public, nor researchers.

14.
Clin Trials ; 17(1): 99-105, 2020 02.
Artículo en Inglés | MEDLINE | ID: mdl-31450958

RESUMEN

BACKGROUND: To improve reporting transparency and research integrity, some journals have begun publishing study protocols and statistical analysis plans alongside trial publications. We sought to assess the overall availability and characteristics of protocols and statistical analysis plans of randomized clinical trials published in the top five (by impact factor) general medicine journals. METHODS: All randomized clinical trials published in Annals of Internal Medicine, BMJ, JAMA, Lancet, and NEJM in 2016 were identified. For each randomized clinical trial, we searched for protocols and statistical analysis plans on journal websites (including supplementary material) and in the article, for example, a referenced publication or link to trial or institutional website. Characteristics of randomized clinical trials were extracted from the publication and clinical trial registry. A detailed assessment of protocols and statistical analysis plans was conducted in a 20% random sample of randomized clinical trials. RESULTS: Protocols were available for 299 (82%) trials, ranging from 50% in BMJ to >95% in NEJM and JAMA. Statistical analysis plans were available for 182 (50%) trials and varied from <10% for Annals of Internal Medicine, BMJ, and Lancet to 92% for NEJM. Of the 76 randomized clinical trials in the 20% random sample, 63 (83%) had a protocol but less than half (31; 44%) included an a priori (dated prior to patient enrollment) version of the protocol. Statistical analysis plans were available for 35 (46%) trials, and only 5 (7%) included an a priori version. CONCLUSION: Protocols and statistical analysis plans are publicly available for the majority of trials. However, the a priori versions of these documents are only available for a minority of trials. More attention must be paid to ensuring the public availability of a priori versions.


Asunto(s)
Protocolos de Ensayos Clínicos como Asunto , Publicaciones Periódicas como Asunto , Edición , Ensayos Clínicos Controlados Aleatorios como Asunto , Estudios Transversales , Humanos , Factor de Impacto de la Revista , Modelos Estadísticos , Proyectos de Investigación
18.
J Am Pharm Assoc (2003) ; 59(2): 195-201, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-30661956

RESUMEN

OBJECTIVES: To evaluate the degree to which health care professionals and patients receive consistent messages regarding the possible harms of statins. DESIGN: Cross-sectional study of prescribing information (PI), patient package inserts (PPIs), and pharmacy leaflets for 8 statins approved by the U.S. Food and Drug Adminstration. SETTING: Not applicable. PARTICIPANTS: Not applicable. MAIN OUTCOME MEASURES: All passages describing 7 adverse events (diarrhea, arthralgia, dyspepsia, confusion, memory loss, rhabdomyolysis, and kidney failure) were extracted from PIs, PPIs, and pharmacy leaflets. For each type of information source and adverse event (drug-harm pair), 2 reviewers independently judged passages as indicating either a confirmed, unconfirmed, or mixed causal relationship between statin and adverse event (drug-harm pair). Disagreements were resolved through consensus, and the consistency between information sources was calculated. RESULTS: PI and PPI consistently conveyed the relationship between a given statin and given adverse event (either both "confirmed" or both "unconfirmed") in 12 of 17 evaluable drug-harm pairs. PPIs and pharmacy leaflets were consistent in 10 of 10 evaluable drug-harm pairs. PIs indicated a confirmed, causal relationship in 15 drug-harm pairs that were not mentioned in pharmacy leaflets. Likewise, PPIs indicated a confirmed, causal relationship in 7 drug-harm pairs that were not listed in pharmacy leaflets. CONCLUSION: Despite the widespread use of statins, we discovered considerable ambiguity in language used to describe the evidence concerning their possible harms and variable consistency between PIs, PPIs, and pharmacy leaflets. Further study is needed to understand the reason why pharmacy leaflets did not list, in 15 cases, adverse events that PIs indicated were causally related to the statin.


Asunto(s)
Etiquetado de Medicamentos/normas , Inhibidores de Hidroximetilglutaril-CoA Reductasas/efectos adversos , Folletos , Servicios Farmacéuticos , Estudios Transversales , Humanos , Inhibidores de Hidroximetilglutaril-CoA Reductasas/administración & dosificación
19.
BMJ Evid Based Med ; 23(6): 210-217, 2018 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-30309870

RESUMEN

Reporting bias is a major threat to the validity and credibility of systematic reviews. This article outlines the rationale for accessing clinical study reports and other regulatory documents (regulatory data) as a means of addressing reporting bias and identifies factors that may help decide whether (or not) to include regulatory data in systematic reviews. The article also describes the origins and current state of regulatory data access and summarises a survey of current systematic reviewers' practices in considering regulatory data for inclusion in systematic reviews. How to access and extract regulatory data is not addressed. Organisations and other stakeholders such as Cochrane should encourage the use of data from clinical study reports as an important source of data in reviews of pharmaceutical interventions particularly when the intervention in question is of high importance and the risk of reporting bias is great.


Asunto(s)
Medicina Basada en la Evidencia/métodos , Informe de Investigación , Revisiones Sistemáticas como Asunto , Sesgo , Humanos , Proyectos de Investigación
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