From Standardization to Adaptation: Clinical Trials and the Moral Economy of Anticipation

Abstract

Hailed as the gold standard, the randomized controlled trial (RCT) occupies a hegemonic position at the top of evidence-based medicine’s hierarchy of knowledge. It is testament to the methodology’s capacity for standardization that it can so readily be spoken of in the singular: the RCT. Under what conditions, then, is it possible to speak of change in the gold standard? Since the 1950s, alternative versions of the RCT have been advocated for under the banner of ‘adaptive design’. Adaptive designs allow investigators to make pre-planned changes to a trial on the basis of accruing information while the experiment is ongoing. Initially a niche topic of methodological debate among biostatisticians, the approach is becoming widespread in mainstream drug development. A genealogical analysis exposes the discursive moves used to justify and popularize adaptation, from a focus on patient well-being and the greater good in the 1960s and 1970s, to efficiency and virtualism in the 1990s and 2000s. Changing discourses of time and patienthood have facilitated a move away from standardization as the singular logic of trials towards an appreciation of flexibility, undergirded by probabilistic methodologies. Adams et al.’s [(2009). Anticipation: Technoscience, life, affect, temporality, Subjectivity, 28, pp. 246–265] conceptual framework of anticipation illuminates this evolving moral economy of medical research, in which modes of knowledge production which claim to know the future are supplanting the traditional certainties of fixed and standardized experimental designs. Predictable uncertainty is the currency of this emerging economy, which capitalizes on computer simulation and ever more sophisticated tools of prediction to leverage credibility.

Key Words:

• clinical trials
• adaptive design
• time
• patients
• statistics
• anticipation

Disclosure Statement

No potential conflict of interest was reported by the authors.

ORCiD

Catherine M. Montgomery http://orcid.org/0000-0002-5829-6137

Notes

1 For a complete overview of the designs and debates of the Ebola clinical trials, see the special issue ‘Clinical Trials During the Ebola Crisis: A Series of Articles and Commentaries Describing the Challenges of Conducting Clinical Research During a Lethal Epidemic’ in Clinical Trials (2016) 13 (1).

2 In oncology, the integration of research and care is particularly notable, with clinical trials in the field of pediatric oncology, in particular, said to define the standard of care. The majority of children (approximately 70%) suffering from cancer enrol in one or more clinical trials (Unguru, 2011; Salman et al., 2014).

3 Based in Washington, PhRMA represents 56 biotechnology companies and ‘advocates in the U.S. and around the world on public policy issues critical to the discovery and development of innovative medicines’ (http://www.phrma.org/about). For further analysis of the influence of PhRMA on Congress and on the FDA, see (Davis and Abraham, 2013; Freudenberg, 2014).

4 Search conducted in Nexis® on 17 March 2015. Term ‘adaptive design’ searched in all 163 sources categorized as Industry = Pharmaceuticals and Biotechnology.

Additional information

Funding

This work was supported by the Nederlandse Organisatie voor Wetenschappelijk Onderzoek (Netherlands Organisation for Scientific Research) [grant number 451-11-003].