Biobanks accumulate huge amounts of research findings, including participants' genomic data. Increasingly this leads to biobanks receiving research results that could be of clinical significance to biobank participants. The EU Horizon 2020 Project 'Genetics Clinic of the Future' surveyed European biobanks' perceptions of the legal and regulatory requirements for communicating individual research results to donors. The goal was to gain background knowledge for possible future guidelines, especially relating to the consent process. The Survey was implemented using a web-based Webropol tool. The questionnaire was sent at the end of 2015 to 351 European biobanks in 13 countries that are members of BBMRI-ERIC (Biobanking and Biomolecular Resources Research Infrastructure–European Research Infrastructure Consortium). Seventy-two biobanks responded to the survey, representing each of the 13 BBMRI Member States. Respondents were mainly individuals responsible for the governance of biobanks. The replies indicate that the majority of the respondents thought that their national legislation allowed them to contact participants to communicate results, and that research participants had the right to request their results. However, respondents' understanding of their national legislation varied even within member states. Our results indicate that legislation applied to biobanks in many countries may be scattered and difficult to interpret. In BBMRI-ERIC, there is an ongoing discussion about the need for European recommendations on sharing genomic biobank results with donors, which may pave the way for more coherent global guidelines. Our results form a basis for this work.
Dynamic consent (DC) is an approach to consent that enables people, through an interactive digital interface, to make granular decisions about their ongoing participation. This approach has been explored within biomedical research, in fields such as biobanking and genomics, where ongoing contact is required with participants. It is posited that DC can enhance decisional autonomy and improve researcher–participant communication. Currently, there is a lack of evidence about the measurable effects of DC-based tools. This article outlines a framework for DC evaluation and reporting. The article draws upon the evidence for enhanced modes of informed consent for research as the basis for a logic model. It outlines how future evaluations of DC should be designed to maximize their quality, replicability, and relevance based on this framework. Finally, the article considers best-practice for reporting studies that assess DC, to enable future research and implementation to build upon the emerging evidence base.
In: Koivula , R W , Heggie , A , Barnett , A , Cederberg , H , Hansen , T H , Koopman , A D , Ridderstrale , M , Rutters , F , Vestergaard , H , Gupta , R , Herrgard , S , Heymans , M W , Perry , M H , Rauh , S , Siloaho , M , Teare , H J A , Thorand , B , Bell , J , Brunak , S , Frost , G , Jablonka , B , Mari , A , McDonald , T J , Dekker , J M , Hansen , T , Hattersley , A , Laakso , M , Pedersen , O , Koivisto , V , Ruetten , H , Walker , M , Pearson , E & Franks , P W 2014 , ' Discovery of biomarkers for glycaemic deterioration before and after the onset of type 2 diabetes: rationale and design of the epidemiological studies within the IMI DIRECT Consortium ' , Diabetologia , vol. 57 , no. 6 , pp. 1132-1142 . https://doi.org/10.1007/s00125-014-3216-x
Aims/hypothesis The DIRECT (Diabetes Research on Patient Stratification) Study is part of a European Union Framework 7 Innovative Medicines Initiative project, a joint undertaking between four industry and 21 academic partners throughout Europe. The Consortium aims to discover and validate biomarkers that: (1) predict the rate of glycaemic deterioration before and after type 2 diabetes onset; (2) predict the response to diabetes therapies; and (3) help stratify type 2 diabetes into clearly definable disease subclasses that can be treated more effectively than without stratification. This paper describes two new prospective cohort studies conducted as part of DIRECT. Methods Prediabetic participants (target sample size 2,200-2,700) and patients with newly diagnosed type 2 diabetes (target sample size similar to 1,000) are undergoing detailed metabolic phenotyping at baseline and 18 months and 36 months later. Abdominal, pancreatic and liver fat is assessed using MRI. Insulin secretion and action are assessed using frequently sampled OGTTs in non-diabetic participants, and frequently sampled mixed-meal tolerance tests in patients with type 2 diabetes. Biosamples include venous blood, faeces, urine and nail clippings, which, among other biochemical analyses, will be characterised at genetic, transcriptomic, metabolomic, proteomic and metagenomic levels. Lifestyle is assessed using high-resolution triaxial accelerometry, 24 h diet record, and food habit questionnaires. Conclusinos/interpretation DIRECT will yield an unprecedented array of biomaterials and data. This resource, available through managed access to scientists within and outside the Consortium, will facilitate the development of new treatments and therapeutic strategies for the prevention and management of type 2 diabetes.
The DIRECT (Diabetes Research on Patient Stratification) Study is part of a European Union Framework 7 Innovative Medicines Initiative project, a joint undertaking between four industry and 21 academic partners throughout Europe. The Consortium aims to discover and validate biomarkers that: (1) predict the rate of glycaemic deterioration before and after type 2 diabetes onset; (2) predict the response to diabetes therapies; and (3) help stratify type 2 diabetes into clearly definable disease subclasses that can be treated more effectively than without stratification. This paper describes two new prospective cohort studies conducted as part of DIRECT.
In: Koivula , R W , Heggie , A , Barnett , A , Cederberg , H , Hansen , T H , Koopman , A D , Ridderstråle , M , Rutters , F , Vestergaard , H , Gupta , R , Herrgård , S , Heymans , M W , Perry , M H , Rauh , S , Siloaho , M , Teare , H J A , Thorand , B , Bell , J , Brunak , S , Frost , G , Jablonka , B , Mari , A , McDonald , T J , Dekker , J M , Hansen , T , Hattersley , A , Laakso , M , Pedersen , O , Koivisto , V , Ruetten , H , Walker , M , Pearson , E , Franks , P W & DIRECT Consortium 2014 , ' Discovery of biomarkers for glycaemic deterioration before and after the onset of type 2 diabetes : rationale and design of the epidemiological studies within the IMI DIRECT Consortium ' Diabetologia , vol 57 , no. 6 , pp. 1132-1142 . DOI:10.1007/s00125-014-3216-x
Aims/hypothesis The DIRECT (Diabetes Research on Patient Stratification) Study is part of a European Union Framework 7 Innovative Medicines Initiative project, a joint undertaking between four industry and 21 academic partners throughout Europe. The Consortium aims to discover and validate biomarkers that: (1) predict the rate of glycaemic deterioration before and after type 2 diabetes onset; (2) predict the response to diabetes therapies; and (3) help stratify type 2 diabetes into clearly definable disease subclasses that can be treated more effectively than without stratification. This paper describes two new prospective cohort studies conducted as part of DIRECT. Methods Prediabetic participants (target sample size 2,200–2,700) and patients with newly diagnosed type 2 diabetes (target sample size ~1,000) are undergoing detailed metabolic phenotyping at baseline and 18 months and 36 months later. Abdominal, pancreatic and liver fat is assessed using MRI. Insulin secretion and action are assessed using frequently sampled OGTTs in non-diabetic participants, and frequently sampled mixed-meal tolerance tests in patients with type 2 diabetes. Biosamples include venous blood, faeces, urine and nail clippings, which, among other biochemical analyses, will be characterised at genetic, transcriptomic, metabolomic, proteomic and metagenomic levels. Lifestyle is assessed using high-resolution triaxial accelerometry, 24 h diet record, and food habit questionnaires. Conclusions/interpretation DIRECT will yield an unprecedented array of biomaterials and data. This resource, available through managed access to scientists within and outside the Consortium, will facilitate the development of new treatments and therapeutic strategies for the prevention and management of type 2 diabetes.
In: Eriksen , R , Perez , I G , Posma , J M , Haid , M , Sharma , S , Prehn , C , Thomas , L E , Koivula , R W , Bizzotto , R , Mari , A , Giordano , G N , Pavo , I , Schwenk , J M , De Masi , F , Tsirigos , K D , Brunak , S , Viñuela , A , Mahajan , A , McDonald , T J , Kokkola , T , Rutter , F , Teare , H , Hansen , T H , Fernandez , J , Jones , A , Jennison , C , Walker , M , McCarthy , M I , Pedersen , O , Ruetten , H , Forgie , I , Bell , J D , Pearson , E R , Franks , P W , Adamski , J , Holmes , E & Frost , G 2020 , ' Dietary metabolite profiling brings new insight into the relationship between nutrition and metabolic risk : An IMI DIRECT study ' , EBioMedicine , vol. 58 , 102932 . https://doi.org/10.1016/j.ebiom.2020.102932
Background: Dietary advice remains the cornerstone of prevention and management of type 2 diabetes (T2D). However, understanding the efficacy of dietary interventions is confounded by the challenges inherent in assessing free living diet. Here we profiled dietary metabolites to investigate glycaemic deterioration and cardiometabolic risk in people at risk of or living with T2D. Methods: We analysed data from plasma collected at baseline and 18-month follow-up in individuals from the Innovative Medicines Initiative (IMI) Diabetes Research on Patient Stratification (DIRECT) cohort 1 n = 403 individuals with normal or impaired glucose regulation (prediabetic) and cohort 2 n = 458 individuals with new onset of T2D. A dietary metabolite profile model (T pred ) was constructed using multivariable regression of 113 plasma metabolites obtained from targeted metabolomics assays. The continuous T pred score was used to explore the relationships between diet, glycaemic deterioration and cardio-metabolic risk via multiple linear regression models. Findings: A higher T pred score was associated with healthier diets high in wholegrain (β=3.36 g, 95% CI 0.31, 6.40 and β=2.82 g, 95% CI 0.06, 5.57) and lower energy intake (β=-75.53 kcal, 95% CI -144.71, -2.35 and β=-122.51 kcal, 95% CI -186.56, -38.46), and saturated fat (β=-0.92 g, 95% CI -1.56, -0.28 and β=–0.98 g, 95% CI -1.53, -0.42 g), respectively for cohort 1 and 2. In both cohorts a higher T pred score was also associated with lower total body adiposity and favourable lipid profiles HDL-cholesterol (β=0.07 mmol/L, 95% CI 0.03, 0.1), (β=0.08 mmol/L, 95% CI 0.04, 0.1), and triglycerides (β=-0.1 mmol/L, 95% CI -0.2, -0.03), (β=-0.2 mmol/L, 95% CI -0.3, -0.09), respectively for cohort 1 and 2. In cohort 2, the T pred score was negatively associated with liver fat (β=-0.74%, 95% CI -0.67, -0.81), and lower fasting concentrations of HbA1c (β=-0.9 mmol/mol, 95% CI -1.5, -0.1), glucose (β=-0.2 mmol/L, 95% CI -0.4, -0.05) and insulin (β=-11.0 pmol/mol, 95% CI -19.5, -2.6). Longitudinal analysis showed at 18-month follow up a higher T pred score was also associated lower total body adiposity in both cohorts and lower fasting glucose (β=-0.2 mmol/L, 95% CI -0.3, -0.01) and insulin (β=-9.2 pmol/mol, 95% CI -17.9, -0.4) concentrations in cohort 2. Interpretation: Plasma dietary metabolite profiling provides objective measures of diet intake, showing a relationship to glycaemic deterioration and cardiometabolic health. Funding: This work was supported by the Innovative Medicines Initiative Joint Undertaking under grant agreement no. 115,317 (DIRECT), resources of which are composed of financial contribution from the European Union's Seventh Framework Programme (FP7/2007–2013) and EFPIA companies.