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BACKGROUND: In the diagnosis of obstructive coronary artery disease (CAD), computed tomography (CT) is an accurate, noninvasive alternative to invasive coronary angiography (ICA). However, the comparative effectiveness of CT and ICA in the management of CAD to reduce the frequency of major adverse cardiovascular events is uncertain. METHODS: We conducted a pragmatic, randomized trial comparing CT with ICA as initial diagnostic imaging strategies for guiding the treatment of patients with stable chest pain who had an intermediate pretest probability of obstructive CAD and were referred for ICA at one of 26 European centers. The primary outcome was major adverse cardiovascular events (cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke) over 3.5 years. Key secondary outcomes were procedure-related complications and angina pectoris. RESULTS: Among 3561 patients (56.2% of whom were women), follow-up was complete for 3523 (98.9%). Major adverse cardiovascular events occurred in 38 of 1808 patients (2.1%) in the CT group and in 52 of 1753 (3.0%) in the ICA group (hazard ratio, 0.70; 95% confidence interval [CI], 0.46 to 1.07; P = 0.10). Major procedure-related complications occurred in 9 patients (0.5%) in the CT group and in 33 (1.9%) in the ICA group (hazard ratio, 0.26; 95% CI, 0.13 to 0.55). Angina during the final 4 weeks of follow-up was reported in 8.8% of the patients in the CT group and in 7.5% of those in the ICA group (odds ratio, 1.17; 95% CI, 0.92 to 1.48). CONCLUSIONS: Among patients referred for ICA because of stable chest pain and intermediate pretest probability of CAD, the risk of major adverse cardiovascular events was similar in the CT group and the ICA group. The frequency of major procedure-related complications was lower with an initial CT strategy. (Funded by the European Union Seventh Framework Program and others; DISCHARGE ClinicalTrials.gov number, NCT02400229.).
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Angiografía Coronaria , Enfermedad de la Arteria Coronaria , Tomografía Computarizada por Rayos X , Angina de Pecho/diagnóstico por imagen , Angina de Pecho/etiología , Dolor en el Pecho/diagnóstico por imagen , Dolor en el Pecho/etiología , Angiografía Coronaria/efectos adversos , Enfermedad de la Arteria Coronaria/complicaciones , Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Femenino , Humanos , Masculino , Tomografía Computarizada por Rayos X/efectos adversosRESUMEN
Background Recent trials support the role of cardiac CT in the evaluation of symptomatic patients suspected of having coronary artery disease (CAD); however, body mass index (BMI) has been reported to negatively impact CT image quality. Purpose To compare initial use of CT versus invasive coronary angiography (ICA) on clinical outcomes in patients with stable chest pain stratified by BMI category. Materials and Methods This prospective study represents a prespecified BMI subgroup analysis of the multicenter Diagnostic Imaging Strategies for Patients with Stable Chest Pain and Intermediate Risk of Coronary Artery Disease (DISCHARGE) trial conducted between October 2015 and April 2019. Adult patients with stable chest pain and a CAD pretest probability of 10%-60% were randomly assigned to undergo initial CT or ICA. The primary end point was major adverse cardiovascular events (MACE), including cardiovascular death, nonfatal myocardial infarction, or stroke. The secondary end point was an expanded MACE composite, including transient ischemic attack, and major procedure-related complications. Competing risk analyses were performed using the Fine and Gray subdistribution Cox proportional hazard model to assess the impact of the relationship between BMI and initial management with CT or ICA on the study outcomes, whereas noncardiovascular death and unknown causes of death were considered competing risk events. Results Among the 3457 participants included, 831 (24.0%), 1358 (39.3%), and 1268 (36.7%) had a BMI of less than 25, between 25 and 30, and greater than 30 kg/m2, respectively. No interaction was found between CT or ICA and BMI for MACE (P = .29), the expanded MACE composite (P = .38), or major procedure-related complications (P = .49). Across all BMI subgroups, expanded MACE composite events (CT, 10 of 409 [2.4%] to 23 of 697 [3.3%]; ICA, 26 of 661 [3.9%] to 21 of 422 [5.1%]) and major procedure-related complications during initial management (CT, one of 638 [0.2%] to five of 697 [0.7%]; ICA, nine of 630 [1.4%] to 12 of 422 [2.9%]) were less frequent in the CT versus ICA group. Participants with a BMI exceeding 30 kg/m² exhibited a higher nondiagnostic CT rate (7.1%, P = .044) compared to participants with lower BMI. Conclusion There was no evidence of a difference in outcomes between CT and ICA across the three BMI subgroups. Clinical trial registration no. NCT02400229 © RSNA, 2024 Supplemental material is available for this article.
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Enfermedad de la Arteria Coronaria , Adulto , Humanos , Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Índice de Masa Corporal , Angiografía Coronaria , Alta del Paciente , Estudios Prospectivos , Dolor en el Pecho/diagnóstico por imagenRESUMEN
Background Coronary artery calcium (CAC) has prognostic value for major adverse cardiovascular events (MACE) in asymptomatic individuals, whereas its role in symptomatic patients is less clear. Purpose To assess the prognostic value of CAC scoring for MACE in participants with stable chest pain initially referred for invasive coronary angiography (ICA). Materials and Methods This prespecified subgroup analysis from the Diagnostic Imaging Strategies for Patients With Stable Chest Pain and Intermediate Risk of Coronary Artery Disease (DISCHARGE) trial, conducted between October 2015 and April 2019 across 26 centers in 16 countries, focused on adult patients with stable chest pain referred for ICA. Participants were randomly assigned to undergo either ICA or coronary CT. CAC scores from noncontrast CT scans were categorized into low, intermediate, and high groups based on scores of 0, 1-399, and 400 or higher, respectively. The end point of the study was the occurrence of MACE (myocardial infarction, stroke, and cardiovascular death) over a median 3.5-year follow-up, analyzed using Cox proportional hazard regression tests. Results The study involved 1749 participants (mean age, 60 years ± 10 [SD]; 992 female). The prevalence of obstructive coronary artery disease (CAD) at CT angiography rose from 4.1% (95% CI: 2.8, 5.8) in the CAC score 0 group to 76.1% (95% CI: 70.3, 81.2) in the CAC score 400 or higher group. Revascularization rates increased from 1.7% to 46.2% across the same groups (P < .001). The CAC score 0 group had a lower MACE risk (0.5%; HR, 0.08 [95% CI: 0.02, 0.30]; P < .001), as did the 1-399 CAC score group (1.9%; HR, 0.27 [95% CI: 0.13, 0.59]; P = .001), compared with the 400 or higher CAC score group (6.8%). No significant difference in MACE between sexes was observed (P = .68). Conclusion In participants with stable chest pain initially referred for ICA, a CAC score of 0 showed very low risk of MACE, and higher CAC scores showed increasing risk of obstructive CAD, revascularization, and MACE at follow-up. Clinical trial registration no. NCT02400229 © RSNA, 2024 Supplemental material is available for this article. See also the editorial by Hanneman and Gulsin in this issue.
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Enfermedad de la Arteria Coronaria , Infarto del Miocardio , Adulto , Humanos , Femenino , Persona de Mediana Edad , Calcio , Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Dolor en el Pecho/diagnóstico por imagenRESUMEN
OBJECTIVES: To investigate if the effect of cardiac computed tomography (CT) vs. invasive coronary angiography (ICA) on cardiovascular events differs based on smoking status. MATERIALS AND METHODS: This pre-specified subgroup analysis of the pragmatic, prospective, multicentre, randomised DISCHARGE trial (NCT02400229) involved 3561 patients with suspected coronary artery disease (CAD). The primary endpoint was major adverse cardiovascular events (MACE: cardiovascular death, non-fatal myocardial infarction, or stroke). Secondary endpoints included an expanded MACE composite (MACE, transient ischaemic attack, or major procedure-related complications). RESULTS: Of 3445 randomised patients with smoking data (mean age 59.1 years + / - 9.7, 1151 men), at 3.5-year follow-up, the effect of CT vs. ICA on MACE was consistent across smoking groups (p for interaction = 0.98). The percutaneous coronary intervention rate was significantly lower with a CT-first strategy in smokers and former smokers (p = 0.01 for both). A CT-first strategy reduced the hazard of major procedure-related complications (HR: 0.21, 95% CI: 0.03, 0.81; p = 0.045) across smoking groups. In current smokers, the expanded MACE composite was lower in the CT- compared to the ICA-first strategy (2.3% (8) vs 6.0% (18), HR: 0.38; 95% CI: 0.17, 0.88). The rate of non-obstructive CAD was significantly higher in all three smoking groups in the CT-first strategy. CONCLUSION: For patients with stable chest pain referred for ICA, the clinical outcomes of CT were consistent across smoking status. The CT-first approach led to a higher detection rate of non-obstructive CAD and fewer major procedure-related complications in smokers. CLINICAL RELEVANCE STATEMENT: This pre-specified sub-analysis of the DISCHARGE trial confirms that a CT-first strategy in patients with stable chest pain referred for invasive coronary angiography with an intermediate pre-test probability of coronary artery disease is as effective as and safer than invasive coronary angiography, irrespective of smoking status. TRIAL REGISTRATION: ClinicalTrials.gov NCT02400229. KEY POINTS: ⢠No randomised studies have assessed smoking status on CT effectiveness in symptomatic patients referred for invasive coronary angiography. ⢠A CT-first strategy results in comparable adverse events, fewer complications, and increased coronary artery disease detection, irrespective of smoking status. ⢠A CT-first strategy is safe and effective for stable chest pain patients with intermediate pre-test probability for CAD, including never smokers.
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An effective response to the coronavirus disease 2019 (COVID-19) pandemic requires a better understanding of the biology of the infection and the identification of validated biomarker profiles that would increase the availability, accuracy, and speed of COVID-19 testing. Here, we describe the strategic objectives and action lines of the European Alliance of Medical Research Infrastructures (AMRI), established to improve the research process and tackle challenges related to diagnostic tests and biomarker development. Recommendations include: the creation of a European taskforce for validation of novel diagnostic products, the definition and promotion of criteria for COVID-19 samples biobanking, the identification and validation of biomarkers as clinical endpoints for clinical trials, and the definition of immune biomarker signatures at different stages of the disease. An effective management of the COVID-19 pandemic is possible only if there is a high level of knowledge and coordination between the public and private sectors within a robust quality framework.
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Investigación Biomédica , COVID-19 , Bancos de Muestras Biológicas , Biomarcadores , Prueba de COVID-19 , Humanos , Pandemias , SARS-CoV-2RESUMEN
BACKGROUND: Informed consent forms for clinical research are several and variable at international, national and local levels. According to the literature, they are often unclear and poorly understood by participants. Within the H2020 project CORBEL-Coordinated Research Infrastructures Building Enduring Life-science Services-clinical researchers, researchers in ethical, social, and legal issues, experts in planning and management of clinical studies, clinicians, researchers in citizen involvement and public engagement worked together to provide a minimum set of requirements for informed consent in clinical studies. METHODS: The template was based on a literature review including systematic reviews and guidelines searched on PubMed, Embase, Cochrane Library, NICE, SIGN, GIN, and Clearinghouse databases, and on comparison of templates gathered through an extensive search on the websites of research institutes, national and international agencies, and international initiatives. We discussed the draft versions step-by-step and then we referred to it as the "matrix" to underline its modular character and indicate that it allows adaptation to the context in which it will be used. The matrix was revised by representatives of two international patient groups. RESULTS: The matrix covers the process of ensuring that the appropriate information, context and setting are provided so that the participant can give truly informed consent. It addresses the key topics and proposes wording on how to clarify the meaning of placebo and of non-inferiority studies, the importance of individual participants' data sharing, and the impossibility of knowing in advance how the data might be used in future studies. Finally, it presents general suggestions on wording, format, and length of the information sheet. CONCLUSIONS: The matrix underlines the importance of improving the process of communication, its proper conditions (space, time, setting), and addresses the participants' lack of knowledge on how clinical research is conducted. It can be easily applied to a specific setting and could be a useful tool to identify the appropriate informed consent format for any study. The matrix is mainly intended to support multicentre interventional randomized clinical studies, but several suggestions also apply to non-interventional research.
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Estudios Clínicos como Asunto , Consentimiento Informado , Humanos , Difusión de la Información , Proyectos de Investigación , InvestigadoresRESUMEN
French clinical investigation centers (CICs) are academic platforms dedicated to clinical research. The QUALI-CIC working group helps to improve and harmonize practices within the CIC network. After some years of implementation, the manual of good professional practices of CICs (MGPP CIC) completed in 2010, needed to be revised to best fit with the large panel of CIC activities. The aim was also to make it more accurate and to reinforce requirements about participants safety and data security. In its second version published in the present article, the MGPP CIC includes 255 items divided into 15 chapters. An explanatory document, currently being drafted, will complete the manual to facilitate its implementation.
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Centros Médicos Académicos , Investigación Biomédica/normas , Manuales como Asunto , Garantía de la Calidad de Atención de Salud , Francia , HumanosRESUMEN
Importance: The effectiveness and safety of computed tomography (CT) and invasive coronary angiography (ICA) in different age groups is unknown. Objective: To determine the association of age with outcomes of CT and ICA in patients with stable chest pain. Design, Setting, and Participants: The assessor-blinded Diagnostic Imaging Strategies for Patients With Stable Chest Pain and Intermediate Risk of Coronary Artery Disease (DISCHARGE) randomized clinical trial was conducted between October 2015 and April 2019 in 26 European centers. Patients referred for ICA with stable chest pain and an intermediate probability of obstructive coronary artery disease were analyzed in an intention-to-treat analysis. Data were analyzed from July 2022 to January 2023. Interventions: Patients were randomly assigned to a CT-first strategy or a direct-to-ICA strategy. Main Outcomes and Measures: MACE (ie, cardiovascular death, nonfatal myocardial infarction, or stroke) and major procedure-related complications. The primary prespecified outcome of this secondary analysis of age was major adverse cardiovascular events (MACE) at a median follow-up of 3.5 years. Results: Among 3561 patients (mean [SD] age, 60.1 [10.1] years; 2002 female [56.2%]), 2360 (66.3%) were younger than 65 years, 982 (27.6%) were between ages 65 to 75 years, and 219 (6.1%) were older than 75 years. The primary outcome was MACE at a median (IQR) follow-up of 3.5 (2.9-4.2) years for 3523 patients (99%). Modeling age as a continuous variable, age, and randomization group were not associated with MACE (hazard ratio, 1.02; 95% CI, 0.98-1.07; P for interaction = .31). Age and randomization group were associated with major procedure-related complications (odds ratio, 1.15; 95% CI, 1.05-1.27; P for interaction = .005), which were lower in younger patients. Conclusions and Relevance: Age did not modify the effect of randomization group on the primary outcome of MACE but did modify the effect on major procedure-related complications. Results suggest that CT was associated with a lower risk of major procedure-related complications in younger patients. Trial Registration: ClinicalTrials.gov Identifier: NCT02400229.
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Enfermedad de la Arteria Coronaria , Femenino , Humanos , Persona de Mediana Edad , Dolor en el Pecho/etiología , Dolor en el Pecho/diagnóstico , Angiografía Coronaria/métodos , Enfermedad de la Arteria Coronaria/complicaciones , Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Tomografía Computarizada por Rayos X , Masculino , AncianoRESUMEN
In pediatric clinical research, it is essential to implement ethical and regulatory requirements, training, and facilities to grant the proper management of specimens, considering that blood sampling may be difficult, the number of specimens is usually limited, and all efforts should be made to minimize sample volumes. In the context of the Pediatric Clinical Research Infrastructure Network (PedCRIN) project, an easy-to-use tool has been developed to guide investigators and sponsors in managing specimens and associated data in compliance with the applicable European rules in the context of pediatric clinical trials. Key topics and research questions to properly manage biosamples and related data in the context of pediatric trials were identified by PedCRIN partners; the current European regulatory/ethical and legal resources were searched for and analyzed; the items/measures/procedures to ensure regulatory compliance of a pediatric trial with regards to biosamples were defined. A checklist of the key items to be considered for the management of biological samples in pediatric clinical trials in compliance with the European applicable rules and legislation, was prepared. It is publicly available on the PedCRIN website https://ecrin.org/projects/pedcrin. Five different topics were covered: consent and assent; minimizing harm and maximizing welfare; sampling volume; skills, training and facilities required for sampling; and long-term storage of biological material. This exercise addressed a specific need in the field of pediatric research to implement ad hoc procedures for specimen handling. In fact, specific guidance on the management of biosamples in pediatrics is not available.
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Proyectos de Investigación , Investigadores , Niño , Humanos , Ensayos Clínicos como AsuntoRESUMEN
OBJECTIVE: To compare cardiac computed tomography (CT) with invasive coronary angiography (ICA) as the initial strategy in patients with diabetes and stable chest pain. RESEARCH DESIGN AND METHODS: This prespecified analysis of the multicenter DISCHARGE trial in 16 European countries was performed in patients with stable chest pain and intermediate pretest probability of coronary artery disease. The primary end point was a major adverse cardiac event (MACE) (cardiovascular death, nonfatal myocardial infarction, or stroke), and the secondary end point was expanded MACE (including transient ischemic attacks and major procedure-related complications). RESULTS: Follow-up at a median of 3.5 years was available in 3,541 patients of whom 557 (CT group n = 263 vs. ICA group n = 294) had diabetes and 2,984 (CT group n = 1,536 vs. ICA group n = 1,448) did not. No statistically significant diabetes interaction was found for MACE (P = 0.45), expanded MACE (P = 0.35), or major procedure-related complications (P = 0.49). In both patients with and without diabetes, the rate of MACE did not differ between CT and ICA groups. In patients with diabetes, the expanded MACE end point occurred less frequently in the CT group than in the ICA group (3.8% [10 of 263] vs. 8.2% [24 of 294], hazard ratio [HR] 0.45 [95% CI 0.22-0.95]), as did the major procedure-related complication rate (0.4% [1 of 263] vs. 2.7% [8 of 294], HR 0.30 [95% CI 0.13 - 0.63]). CONCLUSIONS: In patients with diabetes referred for ICA for the investigation of stable chest pain, a CT-first strategy compared with an ICA-first strategy showed no difference in MACE and may potentially be associated with a lower rate of expanded MACE and major procedure-related complications.
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Enfermedad de la Arteria Coronaria , Diabetes Mellitus , Humanos , Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Angiografía Coronaria/métodos , Tomografía Computarizada por Rayos X , Dolor en el Pecho , Diabetes Mellitus/epidemiología , Angiografía por Tomografía Computarizada , Valor Predictivo de las PruebasRESUMEN
Clinical Investigation Centres (CICs) are academic organisations for performing clinical studies. They are a part of a national network which is co-ordinated by French national institute for health and medical research (Inserm), and the head office of healthcare provision (DGOS). There are working groups and specialised networks within the overall CIC network. The Harmonisation of CIC Procedures (HPCIC) group wrote a manual of good professional practices for clinical research. This manual is described here. This manual was written by consensus. It was approved by the coordinators of all CICs, external experts, and validated by representatives of both Inserm and the General directorate of healthcare provision (DGOS). The CIC Good Professional Practices manual is a guide divided into two sections. The first section covers the general management of a CIC (common to all CICs). The second section covers the core activities of CICs, running clinical studies (clinical study coordination, clinical investigation, data management, statistical analysis, valorisation). This manual is available for all CICs and any other clinical research organisations. It will serve as a basis for CIC self-quality evaluation, audits between CICs, and external audits. This manual shows how much the CICs want to standardise practices and procedures nationwide to offer their partners the best quality in performing clinical studies.
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Clinical Investigation Centres (CICs) are academic organisations for performing clinical studies. They are a part of a national network which is co-ordinated by French national institute for health and medical research (Inserm), and the head office of healthcare provision (DGOS). There are working groups and specialised networks within the overall CIC network. The Harmonisation of CIC Procedures (HPCIC) group wrote a manual of good professional practices for clinical research. This manual is described here. This manual was written by consensus. It was approved by the coordinators of all CICs, external experts, and validated by representatives of both Inserm and the General directorate of healthcare provision (DGOS). The CIC Good Professional Practices manual is a guide divided into two sections. The first section covers the general management of a CIC (common to all CICs). The second section covers the core activities of CICs, running clinical studies (clinical study coordination, clinical investigation, data management, statistical analysis, valorisation). This manual is available for all CICs and any other clinical research organisations. It will serve as a basis for CIC self-quality evaluation, audits between CICs, and external audits. This manual shows how much the CICs want to standardise practices and procedures nationwide to offer their partners the best quality in performing clinical studies.
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Investigación Biomédica/normas , Investigación Biomédica/organización & administración , Francia , Guías como Asunto , Humanos , Auditoría Administrativa , Reproducibilidad de los ResultadosRESUMEN
OBJECTIVE: To assess the comparative effectiveness of computed tomography and invasive coronary angiography in women and men with stable chest pain suspected to be caused by coronary artery disease. DESIGN: Prospective, multicentre, randomised pragmatic trial. SETTING: Hospitals at 26 sites in 16 European countries. PARTICIPANTS: 2002 (56.2%) women and 1559 (43.8%) men (total of 3561 patients) with suspected coronary artery disease referred for invasive coronary angiography on the basis of stable chest pain and a pre-test probability of obstructive coronary artery disease of 10-60%. INTERVENTION: Both women and men were randomised 1:1 (with stratification by gender and centre) to a strategy of either computed tomography or invasive coronary angiography as the initial diagnostic test (1019 and 983 women, and 789 and 770 men, respectively), and an intention-to-treat analysis was performed. Randomised allocation could not be blinded, but outcomes were assessed by investigators blinded to randomisation group. MAIN OUTCOME MEASURES: The primary endpoint was major adverse cardiovascular events (MACE; cardiovascular death, non-fatal myocardial infarction, or non-fatal stroke). Key secondary endpoints were an expanded MACE composite (cardiovascular death, non-fatal myocardial infarction, non-fatal stroke, transient ischaemic attack, or major procedure related complication) and major procedure related complications. RESULTS: Follow-up at a median of 3.5 years was available in 98.9% (1979/2002) of women and in 99.0% (1544/1559) of men. No statistically significant gender interaction was found for MACE (P=0.29), the expanded MACE composite (P=0.45), or major procedure related complications (P=0.11). In both genders, the rate of MACE did not differ between the computed tomography and invasive coronary angiography groups. In men, the expanded MACE composite endpoint occurred less frequently in the computed tomography group than in the invasive coronary angiography group (22 (2.8%) v 41 (5.3%); hazard ratio 0.52, 95% confidence interval 0.31 to 0.87). In women, the risk of having a major procedure related complication was lower in the computed tomography group than in the invasive coronary angiography group (3 (0.3%) v 21 (2.1%); hazard ratio 0.14, 0.04 to 0.46). CONCLUSION: This study found no evidence for a difference between women and men in the benefit of using computed tomography rather than invasive coronary angiography as the initial diagnostic test for the management of stable chest pain in patients with an intermediate pre-test probability of coronary artery disease. An initial computed tomography scan was associated with fewer major procedure related complications in women and a lower frequency of the expanded MACE composite in men. TRIAL REGISTRATION: NCT02400229ClinicalTrials.gov NCT02400229.
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Enfermedad de la Arteria Coronaria , Infarto del Miocardio , Accidente Cerebrovascular , Femenino , Humanos , Masculino , Angiografía Coronaria/métodos , Enfermedad de la Arteria Coronaria/complicaciones , Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Estudios Prospectivos , Dolor en el Pecho/diagnóstico por imagen , Dolor en el Pecho/etiología , Tomografía Computarizada por Rayos X , Infarto del Miocardio/diagnóstico por imagen , Infarto del Miocardio/epidemiología , Angiografía por Tomografía Computarizada , Valor Predictivo de las PruebasRESUMEN
Obtaining informed consent from parents of critically ill neonates can be challenging. The parental decision-making process is influenced by the severity of the child's condition, the benefit-risk balance, their emotional state and the quality of the relationship with the clinical team. Independent of local legislation, parents may prefer that consent is sought from both. Misconceptions about the absence of risks or unrealistic expectations about benefits should be openly addressed to avoid misunderstandings which may harm the relationship with the clinical team. Continuous consent can be sought where it is unclear whether the free choice of parental consent has been compromised. Obtaining informed consent is a dynamic process building on trusting relationships. It should include open and honest discussions about benefits and risks. Investigators may benefit from training in effective communication. Finally, involving parents in neonatal research including the development of the informed consent form and the process of obtaining consent should be considered standard practice.
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OBJECTIVES: This study aims to identify the sources of funding for investigator-initiated clinical trials (IICTs) in Portugal, and to recommend ways to improve the quality of information collected from clinical trial databases about funding. DESIGN AND METHODS: A systematic search of trial registrations over the last 13 years-using the WHO International Clinical Trials Registry Platform (WHO-ICTRP) and four clinical trials registries (CTRs)-was carried out to identify IICTs in Portugal, used as a case study. Data from the databases were compared with data contained in publications to evaluate the consistency of information on funding sources. The term 'database' is used in this study to refer to both the WHO-ICTRP and the CTRs. When mentioned separately, the WHO-ICTRP is referred to as a 'platform', while the CTRs are referred to as 'registries'. OUTCOME: Suggestions to improve clinical trials databases to clearly identify the funding sources and data ownership in IICTs. RESULTS: Two hundred and eighty-two IICTs were identified in Portugal. Twenty per cent of trials were supported by industry with unclear information on the ownership of the results. Inaccuracy was found in the information about sponsors and funders. The information about funding in all resulting publications (77 out of 133 completed studies) was also inconsistent between databases in 35 out of 77 (45%) of the studies. Notably, 23% of the trials funded by non-profit organisations (n=226) received funds from international and/or national funding agencies. CONCLUSIONS: Identification of IICT funding and ownership of results is unclear in the databases used for this study, which may lead to misunderstandings about the independence of the obtained results. Transparency and accuracy are desirable so that public decision makers and strategic partners can accurately evaluate national performance in this particular type of clinical research.
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Investigación Biomédica/economía , Ensayos Clínicos como Asunto/economía , Recolección de Datos , Bases de Datos Factuales , Humanos , Portugal , Reproducibilidad de los Resultados , Apoyo a la Investigación como AsuntoRESUMEN
INTRODUCTION: In older adults, dementia and depression are associated with individual distress and high societal costs. Music interventions such as group music therapy (GMT) and recreational choir singing (RCS) have shown promising effects, but their comparative effectiveness across clinical subgroups is unknown. This trial aims to determine effectiveness of GMT, RCS and their combination for care home residents and to examine heterogeneity of treatment effects across subgroups. METHODS AND ANALYSIS: This large, pragmatic, multinational cluster-randomised controlled trial with a 2×2 factorial design will compare the effects of GMT, RCS, both or neither, for care home residents aged 65 years or older with dementia and depressive symptoms. We will randomise 100 care home units with ≥1000 residents in total across eight countries. Each intervention will be offered for 6 months (3 months 2 times/week followed by 3 months 1 time/week), with extension allowed if locally available. The primary outcome will be the change in the Montgomery-Åsberg Depression Rating Scale score at 6 months. Secondary outcomes will include depressive symptoms, cognitive functioning, neuropsychiatric symptoms, psychotropic drug use, caregiver burden, quality of life, mortality and costs over at least 12 months. The study has 90% power to detect main effects and is also powered to determine interaction effects with gender, severity and socioeconomic status. ETHICS AND DISSEMINATION: Ethical approval has been obtained for one country and will be obtained for all countries. Results will be presented at national and international conferences and published in scientific journals. TRIAL REGISTRATION NUMBERS: NCT03496675; Pre-results, ACTRN12618000156280.
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Demencia/terapia , Depresión/terapia , Musicoterapia/métodos , Casas de Salud , Terapia Recreativa/métodos , Canto , Anciano , Análisis por Conglomerados , Evaluación Geriátrica , Hogares para Ancianos , Humanos , Estudios Multicéntricos como Asunto , Calidad de Vida , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
BACKGROUND: Randomised clinical trials are key to advancing medical knowledge and to enhancing patient care, but major barriers to their conduct exist. The present paper presents some of these barriers. METHODS: We performed systematic literature searches and internal European Clinical Research Infrastructure Network (ECRIN) communications during face-to-face meetings and telephone conferences from 2013 to 2017 within the context of the ECRIN Integrating Activity (ECRIN-IA) project. RESULTS: The following barriers to randomised clinical trials were identified: inadequate knowledge of clinical research and trial methodology; lack of funding; excessive monitoring; restrictive privacy law and lack of transparency; complex regulatory requirements; and inadequate infrastructures. There is a need for more pragmatic randomised clinical trials conducted with low risks of systematic and random errors, and multinational cooperation is essential. CONCLUSIONS: The present paper presents major barriers to randomised clinical trials. It also underlines the value of using a pan-European-distributed infrastructure to help investigators overcome barriers for multi-country trials in any disease area.
Asunto(s)
Estudios Multicéntricos como Asunto/métodos , Ensayos Clínicos Pragmáticos como Asunto/métodos , Ensayos Clínicos Controlados Aleatorios como Asunto/métodos , Proyectos de Investigación , Actitud del Personal de Salud , Confidencialidad , Conducta Cooperativa , Equipos y Suministros , Europa (Continente) , Medicina Basada en la Evidencia , Conocimientos, Actitudes y Práctica en Salud , Humanos , Estudios Multicéntricos como Asunto/economía , Estudios Multicéntricos como Asunto/legislación & jurisprudencia , Terapia Nutricional , Ensayos Clínicos Pragmáticos como Asunto/economía , Ensayos Clínicos Pragmáticos como Asunto/legislación & jurisprudencia , Ensayos Clínicos Controlados Aleatorios como Asunto/economía , Ensayos Clínicos Controlados Aleatorios como Asunto/legislación & jurisprudencia , Enfermedades Raras/terapia , Proyectos de Investigación/legislación & jurisprudencia , Investigadores , Apoyo a la Investigación como AsuntoRESUMEN
BACKGROUND: Medical devices play an important role in the diagnosis, prevention, treatment and care of diseases. However, compared to pharmaceuticals, there is no rigorous formal regulation for demonstration of benefits and exclusion of harms to patients. The medical device industry argues that the classical evidence hierarchy cannot be applied for medical devices, as randomised clinical trials are impossible to perform. This article aims to identify the barriers for randomised clinical trials on medical devices. METHODS: Systematic literature searches without meta-analysis and internal European Clinical Research Infrastructure Network (ECRIN) communications taking place during face-to-face meetings and telephone conferences from 2013 to 2017 within the context of the ECRIN Integrating Activity (ECRIN-IA) project. RESULTS: In addition to the barriers that exist for all trials, we identified three major barriers for randomised clinical trials on medical devices, namely: (1) randomisation, including timing of assessment, acceptability, blinding, choice of the comparator group and considerations on the learning curve; (2) difficulties in determining appropriate outcomes; and (3) the lack of scientific advice, regulations and transparency. CONCLUSIONS: The present review offers potential solutions to break down the barriers identified, and argues for applying the randomised clinical trial design when assessing the benefits and harms of medical devices.