Perspectives

The history and fate of the gold standard

DOI: http://dx.doi.org/10.1016/S0140-6736(15)60742-5

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For the past half-century, physicians and clinical researchers have remained confident that randomised controlled trials (RCTs) provide the most rigorous test of preventive, diagnostic, and therapeutic interventions. They are ubiquitously referred to as the “gold standard” of empirical biomedical investigation, to the point where this status is often presented as a self-evident starting point in diagnostic or therapeutic evaluation. However, this status has long been contested, ever more so now with the emergence of “big data”, randomised registry trials, and other modes of knowledge production in medicine. In an era of increasing methodological self-reflection, it is useful to step back and examine how and when RCTs became the gold standard and what our aspirations for gold standards reveal about our deeper medical identity.

RCTs had a complicated prehistory, entailing attempts to ensure equivalent active and control groups, the occasional blinding of researchers or subjects, and the development of statistical methods of comparison. They took on their recognisably modern form with the British Medical Research Council's landmark 1948 trial of streptomycin for pulmonary tuberculosis. As statisticians and clinical pharmacologists attempted to make sense of the pharmaceutical revolution after World War 2, the power of RCTs seemed critical. When the 1962 amendments to the US Food and Drug Administration mandated proof of efficacy through “well-controlled” studies—namely, RCTs—before new drug approval, the US Government set the stage for the avalanche of pharmaceutical trials that followed. In the UK throughout the 1960s and 1970s, Archibald Cochrane advocated for the utility of RCTs to sort therapeutic wheat from chaff. His work set the stage for such worldwide champions of rational therapeutic assessment as Thomas Chalmers, Iain Chalmers, David Sackett, and their colleagues.

But when did RCTs become the “gold standard”? The first instance we have found of the phrase “gold standard” to refer to RCTs came in the pages of The New England Journal of Medicine (NEJM) in December, 1982, in an article written by Alvan Feinstein and Ralph Horwitz. This date surprised us as a very late date for the first usage. Despite extensive searching, we have found no earlier occurrence of “gold standard” in reference to RCTs. We are eager to be proven wrong, but until all textbooks, conference proceedings, journals, and archival collections have been digitised and made full-text searchable, the gold standard of historical research itself remains elusive. Of interest, Feinstein and Horwitz described RCTs not as a gold standard that all research must strive to attain, but as an elusive ideal in many circumstances. Their article was actually a brief in support of the rigorous conduct of other clinical epidemiological research designs. As they remarked, “epidemiological research has become increasingly important because it offers a substitute for the unattainable scientific gold standard of a randomized experimental trial”.

It is worth looking more closely at how and when this notion entered the medical literature. The phrase “gold standard” has a long prehistory in medical journals, but with different meanings. It first appeared in The Lancet in 1870 in a discussion of international coinage and efforts to restore the value of the guinea. Over the next 60 years it occurred repeatedly, in discussions of the actual gold standard: the technique of international finance that links the value of a nation's currency to a set amount of gold, facilitating exchange between different currencies. During the 1930s the term gained a new usage, in discussions of pharmacological use of gold, whether for tuberculosis (unsuccessfully, in 1934) or rheumatoid arthritis (successfully, in 1937). It first appeared in NEJM in 1933, in a humorous riff by Harvey Cushing about the state of surgery and dentistry in the USA. The next five references, through 1959, all referred to the financial gold standard.

Of course, the financial gold standard was rarely seen as a “gold standard”. Instead, it proved controversial for much of its history. Isaac Newton put Britain on a gold standard in 1717, an arrangement formalised by the Royal Mint in 1816. Many other countries followed suit. The system broke down during the economic turmoil of the early 20th century. Inflation during World War 1 forced the UK and other countries off the gold standard. A variant was restored in 1925, but that too had to be abandoned in 1931 during the Great Depression. After preliminary moves by the USA in the 1930s, Richard Nixon finally took the USA off its gold standard in 1971. In 1976 the US Government revised its definition of the dollar to remove all references to gold.

It was, ironically, in this setting—of the final abandonment of the financial gold standard in the USA—that the phrase began to appear in The Lancet and NEJM as something valuable, not merely as a standard of exchange but as the definitive exemplar of quality and reliability. A 1975 Lancet review of new diagnostic criteria described how they set the “gold standard”, providing a new “esperanto of liver disease”. Writing in NEJM in 1979, Victor McKusick called the presentations given by residents at Grand Rounds at Johns Hopkins the “gold standard” for medical communication. Book reviewers described new textbooks as the “gold standard” for their fields. By the early 1980s, clinical researchers described specific procedures as the diagnostic or therapeutic gold standard (eg, adrenal vein catheterisation in The Lancet in 1980, cardiac catheterisation in NEJM in 1981, or haemodialysis in The Lancet in 1982). After the first occurrence in 1982 of gold standard in association with RCTs, the phrase became commonplace, appearing less often within quotation marks, and by the 1990s paralleling the rise of the term evidence-based medicine.

What can we make of the irony of this usage entering medicine in the years after it was abandoned as a tool of international finance in the 1970s? It appeared in diverse therapeutic and diagnostic contexts, reflecting the broad aspirations in medicine for evidentiary solid ground and standardisation throughout this era. But many of its uses in relation to RCTs were critiques, reflecting a legacy of the controversies that had long ensnared those who would claim the epistemic hegemony of RCTs. The debates about RCTs, and about the notion of a medical “gold standard” more generally, often took on religious overtones. Angry about cardiologists' demands that coronary artery bypass grafting be subjected to RCTs, Lawrence Bonchek encouraged surgeons in 1979 to “resist the almost religious fervor of those who would sanctify randomized studies as the only means of learning the truth”. Writing in 1992, P Finbarr Duggan complained that the phrase “gold standard” itself “smacks of dogma” and should be abandoned.

The religious language here may not be coincidental. Arthur Kleinman and others have argued that the emergence of biomedicine within the monotheistic traditions of Europe and the Middle East imbued medicine with a commitment to universal truths, unitary paradigms, and a “single-minded approach to illness and care”. The idea of a gold standard, that there is one best way to do something, whether conduct clinical research, diagnose a disease, or treat a patient, emerges from this underlying commitment. While the desire to base clinical decisions on the best possible evidence reflects a genuine effort to improve the quality of medical care, commitment to a gold standard does more than that. Allegiance to a single approach provides a focus around which communities can organise and rally. But critics have pointed to the dangers of such medical monotheism. As pioneering cardiac surgeon René Favaloro wrote in 1998, reflecting on three decades of debate about bypass grafting, “Randomized trials have developed such high scientific stature and acceptance that they are accorded an almost religious sanctification…If relied on exclusively they may be dangerous.” Quoting Feinstein, Favaloro argued that medical decisions often had to be made without guidance from clinical trials: “To acknowledge this reality requires no loss of reverence, allegiance, or respect for the primacy of randomized trials as a ‘gold standard’ in scientific research.” Favaloro saw this as a particular challenge for surgery, but physicians in all specialties have at times resented the yoke of evidence-based medicine.

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Weighing ingots on the Chancellor Balance at the Royal Mint, Tower Hill, London, UK in the early 20th century

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The past several years have seen increasing calls for an ecumenical approach to clinical research, with more flexible standards for what counts as acceptable study designs. Physicians have developed new methods to extract robust analyses from patient registries and from the ever-growing databases provided by electronic medical records. Will this erode the status of RCTs as a gold standard? The rise of personalised medicine, meanwhile, might make it more difficult to defend gold standards in diagnostic and therapeutic practice. Personalised medicine refocuses clinical attention away from the “typical” patients analysed by RCTs and onto the idiosyncrasies, genetic or otherwise, of individual patients. Has the phrase outlived its usefulness in medicine? It is too soon to tell. Yet even as some physicians turn away from their commitment to medical gold standards, some politicians, newly wary about global financial turbulence, talk of restoring the financial gold standard. Gold standards, whether actual or figurative, represent structures of exchange and aspirations toward stability, despite developments that threaten both.

Cheryl & ethnovet

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Friday, 17 April 2015

Lancet - The history and fate of the gold standard [randomised controlled trials]

The history and fate of the gold standard

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