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A theoretical framework for early human studies: uncertainty, intervention ensembles, and boundaries.

ABSTRACT: Clinical development of novel therapeutics begins with a coordinated sequence of early phase clinical trials. Such early human studies confront a series of methodological and ethical challenges. In what follows, I propose a theoretical framework for early human studies aimed at informing the negotiation of these challenges. At the outset of clinical development, researchers confront a virtually undifferentiated landscape of uncertainty with respect to three variables: outcomes, their probability of occurrence, and operation dimensions needed to effectuate favorable outcomes. Early human trials transform this uncertain landscape into one where there are grounds for belief about risk and benefit for various combined operation dimensions. To accomplish this, studies set out with two aims. First, they identify a set of operation dimensions that, when combined as a package (intervention ensemble), elicits a reasonable probability of a target outcome. Second, they define the boundaries of dimension values within an intervention ensemble. This latter aim entails exposing at least some volunteers in early studies to treatments that are inactive or excessive. I provide examples that illustrate the way early human studies discover and delimit intervention ensembles, and close by offering some implications of this framework for ethics, methodology, and efficiency in clinical development of new interventions.

SUBMITTER: Kimmelman J

PROVIDER: S-EPMC3551836 | biostudies-other | 2012 Sep

REPOSITORIES: biostudies-other

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A theoretical framework for early human studies: uncertainty, intervention ensembles, and boundaries.

Kimmelman Jonathan J

Trials 20120922

Clinical development of novel therapeutics begins with a coordinated sequence of early phase clinical trials. Such early human studies confront a series of methodological and ethical challenges. In what follows, I propose a theoretical framework for early human studies aimed at informing the negotiation of these challenges. At the outset of clinical development, researchers confront a virtually undifferentiated landscape of uncertainty with respect to three variables: outcomes, their probability ...[more]

PMID: 22999017

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Project description:Violence against women (VAW) is a global health problem, which leads to negative sexual, reproductive, mental and physical health outcomes, as well as death in extreme cases. Globally, over 35% of women are reported to have experienced some form of violence, while in Ghana, 37% of women have ever experienced physical violence. Considering that the sustainability of community-based VAW interventions is largely dependent on ownership, this study used the Theoretical Framework of Acceptability (TFA) to assess the COMBAT (Community Based Action Teams) intervention (for example, ethicality, self-efficacy, and intervention coherence) which was implemented to prevent violence against women in Ghana. This qualitative research study was conducted at baseline and end-line of the intervention, which used COMBAT as a vehicle to change social norms on gender and violence in the Central region, Ghana. Participants comprised of adult (women and men) who reside in the Agona District. We analyzed the transcripts from eight (8) Focus Group Discussions conducted within one of the two intervention recipient sites (4 female community FGDs and 4 male community FGDs). Data was analyzed thematically using the Nvivo software version 12. Through the application of the TFA, the findings show that community members perceive VAW as inappropriate at the individual and community levels (ethicality), have good knowledge of the COMBAT intervention and how it works (intervention coherence). Also, the study shows that participants have a positive attitude towards the intervention and its components (positive affective attitude), and could take up components of the intervention, by reporting and seeking for VAW support (positive self-efficacy). There was a perceived reduction in VAW practices in the various communities, as well as a reduction in the abuse of women, thereby improving their well-being (intervention effectiveness). The COMBAT strategy was accepted by the community members hence could be sustained as a culturally appropriate intervention for preventing VAW.

Project description:BackgroundSelf-quantification (SQ) is a way of working in which, by using tracking tools, people aim to collect, manage, and reflect on personal health data to gain a better understanding of their own body, health behavior, and interaction with the world around them. However, health SQ lacks a formal framework for describing the self-quantifiers' activities and their contextual components or constructs to pursue these health related goals. Establishing such framework is important because it is the first step to operationalize health SQ fully. This may in turn help to achieve the aims of health professionals and researchers who seek to make or study changes in the self-quantifiers' health systematically.ObjectiveThe aim of this study was to review studies on health SQ in order to answer the following questions: What are the general features of the work and the particular activities that self-quantifiers perform to achieve their health objectives? What constructs of health SQ have been identified in the scientific literature? How have these studies described such constructs? How would it be possible to model these constructs theoretically to characterize the work of health SQ?MethodsA systematic review of peer-reviewed literature was conducted. A total of 26 empirical studies were included. The content of these studies was thematically analyzed using Activity Theory as an organizing framework.ResultsThe literature provided varying descriptions of health SQ as data-driven and objective-oriented work mediated by SQ tools. From the literature, we identified two types of SQ work: work on data (ie, data management activities) and work with data (ie, health management activities). Using Activity Theory, these activities could be characterized into 6 constructs: users, tracking tools, health objectives, division of work, community or group setting, and SQ plan and rules. We could not find a reference to any single study that accounted for all these activities and constructs of health SQ activity.ConclusionsA Health Self-Quantification Activity Framework is presented, which shows SQ tool use in context, in relation to the goals, plans, and competence of the user. This makes it easier to analyze issues affecting SQ activity, and thereby makes it more feasible to address them. This review makes two significant contributions to research in this field: it explores health SQ work and its constructs thoroughly and it adapts Activity Theory to describe health SQ activity systematically.

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A theoretical framework for early human studies: uncertainty, intervention ensembles, and boundaries.

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A theoretical framework for early human studies: uncertainty, intervention ensembles, and boundaries.

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