Adrian Thorogood

Isolated aerobic exercise and weight loss: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND Aerobic exercise is a common nonpharmacological intervention for the management of obesity. However, the efficacy of isolated aerobic exercise at promoting weight loss is unclear. We conducted a systematic review and meta-analysis to evaluate the efficacy of isolated aerobic exercise programs in overweight and obese populations. METHODS We searched for published randomized controlled trial reports of aerobic exercise through January 20, 2010. Trials with an isolated aerobic exercise intervention were included. A random-effect model was used to synthesize the results of each intervention. RESULTS We identified 14 trials involving 1847 patients. The duration of aerobic exercise programs ranged from 12 weeks to 12 months. Results were pooled for programs with 6-month duration and programs with 12-month duration. Six-month programs were associated with a modest reduction in weight (weighted mean difference [WMD]=-1.6 kg; 95% confidence interval [CI], -1.64 to -1.56) and waist circumference (WMD=-2.12 cm; 95% CI, -2.81 to -1.44). Twelve-month programs also were associated with modest reductions in weight (WMD=-1.7 kg; 95% CI, -2.29 to -1.11) and waist circumference (WMD=-1.95 cm; 95% CI, -3.62 to -0.29). CONCLUSION Moderate-intensity aerobic exercise programs of 6-12 months induce a modest reduction in weight and waist circumference in overweight and obese populations. Our results show that isolated aerobic exercise is not an effective weight loss therapy in these patients. Isolated aerobic exercise provides modest benefits to blood pressure and lipid levels and may still be an effective weight loss therapy in conjunction with diets.

An implementation framework for the feedback of individual research results and incidental findings in research

BackgroundThis article outlines procedures for the feedback of individual research data to participants. This feedback framework was developed in the context of a personalized medicine research project in Canada. Researchers in this domain have an ethical obligation to return individual research results and/or material incidental findings that are clinically significant, valid and actionable to participants. Communication of individual research data must proceed in an ethical and efficient manner. Feedback involves three procedural steps: assessing the health relevance of a finding, re-identifying the affected participant, and communicating the finding. Re-identification requires researchers to break the code in place to protect participant identities. Coding systems replace personal identifiers with a numerical code. Double coding systems provide added privacy protection by separating research data from personal identifying data with a third “linkage” database. A trusted and independent intermediary, the “keyholder”, controls access to this linkage database.DiscussionProcedural guidelines for the return of individual research results and incidental findings are lacking. This article outlines a procedural framework for the three steps of feedback: assessment, re-identification, and communication. This framework clarifies the roles of the researcher, Research Ethics Board, and keyholder in the process. The framework also addresses challenges posed by coding systems. Breaking the code involves privacy risks and should only be carried out in clearly defined circumstances. Where a double coding system is used, the keyholder plays an important role in balancing the benefits of individual feedback with the privacy risks of re-identification.SummaryFeedback policies should explicitly outline procedures for the assessment of findings, and the re-identification and contact of participants. The responsibilities of researchers, the Research Ethics Board, and the keyholder must be clearly defined. We provide general guidelines for keyholders involved in feedback. We also recommend that Research Ethics Boards should not be directly involved in the assessment of individual findings. Hospitals should instead establish formal, interdisciplinary clinical advisory committees to help researchers determine whether or not an uncertain finding should be returned.

A P3G generic access agreement for population genomic studies.

The Public Population Project in Genomics and Society (P3G) is a not-for-profit consortium that provides the international research community with access to the expertise, resources and innovative tools for the harmonization of health and social sciences research. (www.p3gconsortium.org) This “Generic Access Agreement” is a tool developed for use by population genomic studies (also often called biobanks or resources). Over the past decade, in anticipation of expanding demand for access by researchers and industry, large population studies collecting DNA samples worldwide have been developing access principles and policies to ensure ethical and legal access procedures to their resource that respect participant consent (see Table 1). These access policies are now being operationalized into agreements that clearly stipulate the obligations of researchers and institutions who wish to access these resources. The access agreement is typically the final step in the access request process, following the submission and successful review of an application for access.1 Table 1 Existing Agreements, Related Policies and Guidelines Reviewed This P3G Generic Access Agreement attempts to address both the sharing of data and the sharing of materials (i.e. biospecimens). All studies named in Table 1 provide data, while some may additionally allow access to the biological samples themselves, under certain conditions. While many aspects of access apply uniformly between data and materials, there are certain considerations unique to materials, such as their limited and depletable nature. Our proposed Agreement aims to foster some level of uniformity of access by addressing both data and materials together. Access agreements must be drafted clearly, not only so that researchers and their institutions are aware of their obligations, but also in order that “the border between acceptable and unacceptable conduct be clearly delineated and predictable…”2 Explicit sanctions are important in order to respond effectively to any breach. These sanctions must be balanced: harsh enough to deter abuse by researchers and yet not discourage access. We have surveyed available literature, policies, and access agreements in an attempt to identify access norms. These norms have been captured by the P3G “Generic Access Agreement.” Its utility, however, extends beyond suggesting best practices, as it also aims to enhance international harmonization of access procedures. Researchers should not encounter a completely different access procedure each time they apply for access to a study. Mindful of national and cultural heterogeneity, the Agreement seeks to promote scientific knowledge as a common good that should be shared, with appropriate protections in place. The adoption of this unique tool will hopefully improve transparency and interoperability in the sharing of data and samples. It is problematic for population studies to simply rely on existing agreements. First, significant heterogeneity exists between studies, and existing access agreements often reflect peculiarities. The “Generic Access Agreement” seeks to harmonize the core conditions that should be considered by all population studies. Second, existing agreements are often limited to data, and rarely address the use of and access to samples. Third, existing access agreements tend to be conceived in highly legalistic terms. This drafting approach is problematic because it lacks the clarity needed to communicate clear and understandable expectations to researchers as to their commitments. The P3G Generic Access Agreement offers not only a principled analysis of the content of access agreements, it also provides explicit clauses to promote comprehensibility among researchers. It is essential that these agreements are not developed in isolation. Harmonization, at the current implementation stage of population studies, will reinforce international data and sample sharing norms, promote equitable procedures, and improve researcher familiarity with simplified access procedures. Ultimately, some agreement on core bioethical principles3 and the procedures accompanying them will foster an equitable and transparent playing field across population studies and foster their translation into genomic medicine. The P3G “Generic Access Agreement” has drawn on a variety of sources. A selection of existing data or material access agreements among P3G members was reviewed to determine common elements. Access-related documents from population studies – such as publication policies, intellectual property policies and consent forms – were also reviewed to ensure coherent integration. General principles were drawn from existing P3G resources developed to encourage harmonization in access.4,5,6,7 The sources reviewed are listed in Table 1. From the results of our review, a provisional generic access agreement was drafted by the legal team at the Centre of Genomics and Policy of McGill University. The draft agreement was then circulated for two iterations of comments and revisions among the P3G International Steering Committee.8 The resulting version of the agreement was then discussed and approved via the consensus of both the International Steering Committee and the Board of the P3G.9 A few drafting principles were adopted in the preparation of this document: brevity; clear and simple language (as such agreements will often be read by scientists and administrators with limited legal training); and limiting of the template to essential elements so as to encourage uniform treatment of access applications, reduce time for negotiation between the study and researchers, and allow customization for local needs and laws. Certain issues were encountered in the drafting of this document. There was uncertainty concerning the commensurability of procedures for access to data and access to samples. Initially, the team developed a list of “special considerations for samples.” While samples require unique treatment for their quality, security, liability, and disposal upon termination, we found that they could largely be integrated under general conditions used in the access agreement. Significant discussion also went into the Intellectual Property terms. Our definition of “Invention” was drawn from the European Parliament and Council’s Directive on biotechnological inventions.10 The discussion reflected the tension between incentivizing research by allowing limited patent protection of inventions, and promoting the valorization of the resource by allowing future research to build on the findings of past research. The final solution is to protect the potential for downstream patentability while reserving a robust, open license for future use and sublicense. Thus, protection for downstream inventions is explicitly recognized, with reference to international directives that were judged to offer the best balance of the interests. Finally, certain types of conditions mentioned in existing access agreements were not included. The most common reasons were that these conditions were overly technical and legalistic, or too specific to a certain type of study to merit inclusion in a generic access agreement. The success of population studies will depend on their ability to adequately balance promotion and regulation of access. Research will suffer if the conditions of access are too strict; participants will suffer if they are too liberal. The P3G Generic Access Agreement aims to strike this essential balance, to ensure equitable and clear conditions of access for population studies. The Agreement’s successful adoption by the member institutions of P3G will help to establish an international standard for access to population studies. Their effective translation into population health will hopefully be enhanced and promoted.

Reproducibility and reuse of adaptive immune receptor repertoire data

High-throughput sequencing (HTS) of immunoglobulin (B-cell receptor, antibody) and T-cell receptor repertoires has increased dramatically since the technique was introduced in 2009 (1–3). This experimental approach explores the maturation of the adaptive immune system and its response to antigens, pathogens, and disease conditions in exquisite detail. It holds significant promise for diagnostic and therapy-guiding applications. New technology often spreads rapidly, sometimes more rapidly than the understanding of how to make the products of that technology reliable, reproducible, or usable by others. As complex technologies have developed, scientific communities have come together to adopt common standards, protocols, and policies for generating and sharing data sets, such as the MIAME protocols developed for microarray experiments. The Adaptive Immune Receptor Repertoire (AIRR) Community formed in 2015 to address similar issues for HTS data of immune repertoires. The purpose of this perspective is to provide an overview of the AIRR Community’s founding principles and present the progress that the AIRR Community has made in developing standards of practice and data sharing protocols. Finally, and most important, we invite all interested parties to join this effort to facilitate sharing and use of these powerful data sets (join@airr-community.org).

Registered access: a ‘Triple-A’ approach

We propose a standard model for a novel data access tier – registered access – to facilitate access to data that cannot be published in open access archives owing to ethical and legal risk. Based on an analysis of applicable research ethics and other legal and administrative frameworks, we discuss the general characteristics of this Registered Access Model, which would comprise a three-stage approval process: Authentication, Attestation and Authorization. We are piloting registered access with the Demonstration Projects of the Global Alliance for Genomics and Health for which it may provide a suitable mechanism for access to certain data types and to different types of data users.

Public variant databases: liability?

Public variant databases support the curation, clinical interpretation, and sharing of genomic data, thus reducing harmful errors or delays in diagnosis. As variant databases are increasingly relied on in the clinical context, there is concern that negligent variant interpretation will harm patients and attract liability. This article explores the evolving legal duties of laboratories, public variant databases, and physicians in clinical genomics and recommends a governance framework for databases to promote responsible data sharing.Genet Med advance online publication 15 December 2016

APPLaUD: access for patients and participants to individual level uninterpreted genomic data.

BackgroundThere is a growing support for the stance that patients and research participants should have better and easier access to their raw (uninterpreted) genomic sequence data in both clinical and research contexts.Main bodyWe review legal frameworks and literature on the benefits, risks, and practical barriers of providing individuals access to their data. We also survey genomic sequencing initiatives that provide or plan to provide individual access. Many patients and research participants expect to be able to access their health and genomic data. Individuals have a legal right to access their genomic data in some countries and contexts. Moreover, increasing numbers of participatory research projects, direct-to-consumer genetic testing companies, and now major national sequencing initiatives grant individuals access to their genomic sequence data upon request.ConclusionDrawing on current practice and regulatory analysis, we outline legal, ethical, and practical guidance for genomic sequencing initiatives seeking to offer interested patients and participants access to their raw genomic data.

International Guidelines for Privacy in Genomic Biobanking (or the Unexpected Virtue of Pluralism)

This article reviews international privacy norms governing human genomic biobanks and databases, and how they address issues related to consent, secondary use, de- identification, access, security, and governance. A range of international instruments were identified, varying in substance - e.g., human rights, data protection, research ethics, biobanks, and genetics - and legal character. Some norms detail processes for broad consent, namely, that even where potential participants cannot consent to specific users and uses, they should be given clear information on access policies, procedures, and governance structures. Some also give guidance about the conditions under which secondary use of data and samples without consent is appropriate, e.g., where consent is impracticable. International norms exhibit a confusing range of terminology relating to de-identification. They also continue to rely heavily on consent and anonymity as the basis for privacy protection, though governance is becoming more prominent. It may not be fatal that such a plurality of norms apply to biobanking; what is essential is that governance be built on shared values, our common interest in the success of genomic research, and practical tools that incentivize responsible, global sharing.

Population biobanking and international collaboration.

Population-based biobanks promise to be important resources for genetic research. However, the study of normal genomic variation across populations requires the collection of data and biological samples from individuals on a large scale. While international collaboration has become both a scientific and an ethical imperative, international sharing of data and samples poses many challenges. Significant variation persists among the legal and ethical norms governing population biobanks in different jurisdictions. Many of these norms do not clearly provide for international access. To illustrate these problems, we collected and compared applicable legislative instruments, as well as ethical guidelines issued by national, regional, and international bodies. In addition, harmonization is faced with important limitations and may not be sufficient to ensure effective international sharing. Population biobanks are therefore looking for new ways to promote sharing and improve interoperability. The formation of biobank networks and the development of common governance tools are two approaches that are setting the groundwork for international collaboration in genetic research.

Who should have access to genomic data and how should they be held accountable? Perspectives of Data Access Committee members and experts

Facilitating the responsible access to genomic research data is an emerging ethical and scientific imperative. Data Access Committees (DACs) assess the ethical footing and scientific feasibility of the data access requests and evaluate the qualification of applicants to ensure they are bona fide researchers. Through semi-structured interviews, we explored the opinions and experiences of 20 DAC members and experts concerning the users’ qualification criteria and mechanisms to hold users accountable. According to our respondents, such evaluation is necessary to ensure applicants are trustworthy, meet a certain level of expertise or experience and are aware of the rules and the associated concerns with genomic data sharing. The respondents noted, however, that the qualification criteria are fragmented or are poorly delineated at times. Thus, developing qualification criteria seems vital for an objective, fair and responsible access procedure. Similarly, the access review will benefit from using common ways of verifying the users’ affiliations. Furthermore, some DAC members expressed concern over the uncertain oversight of downstream data use, in particular where data are shared across borders. DAC members and experts did not consider current sanctions and enforcement procedures to be crystal clear. Therefore, data sharing policies should address this gap by establishing proportionate sanctions both against data producers and data users’ non-compliance. Users’ home institutes will need to have an active role in keeping oversight on the downstream data uses, considering their ultimate responsibility if wrongdoings happen.