This study examined media and bioethics coverage of the DFSS, which serves as supporting evidence in the CE debate. We specifically focused on how the DFSS is reported in media and bioethics articles that engage in the debate in order to characterize how secondary literature has contributed to the claim that donepezil has CE effects.
Our key findings demonstrate that both media and bioethics articles use the DFSS as support to make strong claims about the use of donepezil for CE purposes, specifically for increasing intelligence and memory. These claims are most pronounced in the headlines and titles of articles that engage in the CE debate, as well as in the colloquialisms that are used to explicitly refer to donepezil within the context of a discussion about CE (Table
2). Emphasis is placed on the possibility that donepezil could affect cognition or intellectual capacity while consistent use of enhancement language implies that this effect is both above one’s “healthy” level of cognition and is a desirable or laudable goal. This supports the previous findings of a study that found that media and bioethics discourses were generally enthusiastic in portraying CE effects of methylphenidate on cognition
. However, we did see a difference between headline and title references to pharmaceutical use as well as to the potential medical use of donepezil (i.e., for memory restoration). While media headlines reference both topics, bioethics titles focus on enhancement and reflect coverage of general issues related to the CE debate. This could indicate that donepezil is rarely examined in the bioethics literature as a cognitive enhancer in its own right (i.e., for memory), but has become part of the larger debate on CE where it is taken to be an illustrative example. Alternatively, it could point to the media interpreting the primary study in different ways, i.e., as both a treatment study and an enhancement study, while bioethics articles unilaterally interpreted the study as evidence of an enhancement effect.
Our analysis of how the results of the DFSS are depicted in media and bioethics articles is consistent with the presentation of strong claims for CE that we found in headlines, titles, and colloquialisms. Amplification of a CE effect occurs both within and across individual articles as the findings of the DFSS are consistently presented at two levels (i.e., specific or extended; Additional file
3 and Additional file
4). In both literatures, the drug effect is reported with reference to three broad categories of characteristics, namely, task performance, memory, and brain, mind, or mental capacity. The way this effect is conveyed, either through improvement language (which could connote a treatment or an enhancement effect) or through explicit enhancement language, and what category of characteristic is emphasized, changes depending on the level at which the result is reported.
We found a clear trend to use explicit CE language and to report effects on memory and brain, mind, and mental capacity when articles report the findings as extended results. This trend is particularly salient in bioethics articles, where the majority of result claims use enhancement language at this level. The proportion of claims about DFSS results made by the media that use enhancement language does increase at the extended level; however, the majority of media claims use improvement language. When improvement language is used at this level, both literatures equally make reference to all three categories of performance improvement.
Conversely, when reporting results at the specific level, both literatures use a higher proportion of improvement rather than explicit enhancement language. Both literatures overwhelmingly report an improvement in task performance, followed by an improvement in memory. An improvement in brain function is only raised as a specific result of the study by bioethics articles. Specific reports of improvements in performance (and memory to a lesser degree) are often associated with discrete tasks, such as flying a flight simulator or performing an emergency procedure. However, further specification of what aspects of these broad characteristics are influenced by donepezil is rare (i.e., executive function, short or long-term memory) as is a precise description of the original level of significance of the findings or what trend contributed to this significant difference (i.e., a decrease in the performance of the pilots in the placebo group). Too few articles use enhancement language at this level to establish any trend.
Evidently, the findings of the DFSS that are reported, as well as the level of detail conveyed, change substantially as they are reported at the specific and extended levels. The direction of this change—from claims of memory and task improvement to claims of enhanced cognitive traits—as articles move away from a focused discussion of the DFSS to report generalized findings suggests that the results of this study may have been hyped as they were used to support the CE debate. However, this data also reflects the duality of study interpretations we found in the headlines, titles, and colloquialisms and may be attributable to the study being interpreted in different ways (i.e., as both a treatment and enhancement study).Our final investigation of how accurately media and bioethics articles translate and present the characteristics of the DFSS (e.g., subjects, study design) showed that overall most study characteristics are accurately identified; only a few are clearly incorrect (Figure
1). However, we found high levels of variability in claims related to the “subjects” and “methods” categories. The information provided on the ‘subjects’ category is straightforward in the DFSS, so these discrepancies stand out. There is a trend to report subject characteristics using the language of the CE debate, e.g., “healthy,” or in relation to the expectation that the drug may be useful for “fighter” or “commercial” pilots (Figure
2). Close examination of the DFSS itself shows that information on the methods used may be difficult for a lay audience to interpret, making accurate restatement of these characteristics legitimately difficult. This variable accuracy in the reporting of study characteristics, combined with our findings related to the reporting of the study’s results, suggests that the strong claims of CE effects associated with donepezil use cannot be accounted for by simple inaccuracy in reporting of the primary paper. More complex interactions seem to be governing the accurate dissemination and interpretation of the findings of the study.
We explore the potential factors involved in the hyped portrayal of the results of the DFSS and the potential ethical implications for society and clinical decision-making in the following discussion points: 1) the magnification of the connection between the results of the DFSS and the CE debate; and, 2) the ethical challenges of hyped claims of CE effects for clinicians.
The magnification of the connection between the results of the DFSS and the CE debate
Further comparison of the results of the DFSS that were reported in media and bioethics articles with the conclusions drawn by the authors of the study in its “discussion” section provides insight into how difficult aspects of the CE debate may have contributed to how the results of the DFSS came to be reported as support for CE.
The findings presented by the DFSS in its “abstract” or “results” section (Table
3) do not claim an enhancement in performance, rather they claim that: “the donepezil group showed greater ability to retain the capacity to perform”
3, abstract). The majority of specific results reported by both media and bioethics articles may be said to have accurately conveyed this result as they claimed improvement in task performance or memory (Additional file
3 and Additional file
In the discussion of the DFSS the authors move from discussing the specific effect they found to generalize an improvement in cognitive performance. They present the qualifying clause: “these results should not be interpreted to advocate widespread use of donepezil in nondemented populations”
 before stating that “[n]onetheless”
, their results are consistent with those of previous studies, which “have reported that cholinesterase inhibitors improve cognitive performance”
. As discussed above in the background section, the interpretation of these results as evidence that donepezil improves flight performance has since been discredited by the authors. A recent review also concluded that the DFSS only demonstrates that donepezil “might improve the retention of training on complex aviation tasks”
 (emphasis added). Finally an additional study that reviewed the level of evidence provided by the DFSS and other studies on acetylcholinesterase inhibitors similarly concluded: “the available evidence does not appear to support the widely cited conclusion that donepezil improves the retention of training”
. Thus, while providing an acceptable lay interpretation of the data, it can be concluded that specific result claims magnify the results of the DFSS.
Beyond generalizing memory to cognition, the authors go on to dedicate the final paragraph of their discussion to raising concerns about CE, directly raising and naming the concept of CE for the first time. Careful examination of this section exposes how difficult aspects of the CE debate, namely understanding the distinction between references to CE that connote a medical term in the AD literature and those that connote CE in healthy individuals and assessing whether a study on an aging population can be considered to be a CE study, may have compounded the challenge of accurately interpreting the study, such that articles’ interpretations are understandably biased towards a CE effect.
Throughout the paragraph, the authors consider what would happen if CE becomes a possibility for intellectually intact individuals and discuss ethical issues tightly linked to the CE debate, such as access, justice, fairness, and regulation. Yet, at the same time, they imply that their study population was not healthy: they discuss the potential demand for CE from aging individuals without AD who seek to remedy their “deficits”
. In this way, the authors make a clear connection between the findings of their study and a CE effect, yet it remains unclear whether they intended to distinguish CE as found in the AD literature from CE discussed in the ethics debate. Thus, the extended result claims of CE effects that were reported in media and bioethics articles seem to be attributable, at least in part, to different messages found in the original publication as the authors attempted to connect their findings to those of other studies and, potentially, to the CE debate.
Problems created in the dissemination of research results emerging from discrepancies within one primary study are certainly not unique to the CE debate or the study we examined. For example, a study on the dissemination of attention deficit hyperactivity disorder (ADHD) research (primary studies that associate polymorphisms of a specific gene with ADHD) found: (1) internal inconsistencies between claims made in the results and those presented in the conclusions; (2) a strong conclusion claim in the summary, while data that limit this conclusion were only present in the results section; and (3) the inappropriate extrapolation of findings to therapeutic prospects
. These data offer support for our finding of a shift in emphasis between the data reported in the results section of the DFSS and the generalized conclusion offered in the study’s discussion that this result may lend support to the CE debate. Previous research on developments in biotechnology, including neurotechnology, has also shown that the majority of authors include both a qualifying clause in their paper that addresses the uncertainty inherent in their data, as well as a main explanation of their data, that is designed to provoke discussion with their peers. Yet, often only the main or simplified explanation is widely disseminated in print media
[20, 76] and observed by stakeholders exposed to media coverage of cognitive enhancement
. Further, explanations that were reported in the media have been found to be inconsistent with what was actually reported in the study, reflecting “different versions of future relevance”
 as the data is interpreted and translated. This phenomenon provides greater insight into our finding that media and bioethics articles reported more generalized conclusions than qualifying clauses and helps to account for the further discrepancy observed in the facts reported by media and bioethics articles.
Finally, the presence of expectations in a field of research has also been found to influence the claims made by authors of both primary and secondary literature
 describes how anticipation of a prospective future is crucial for project development, funding, and creativity. Yet, hype around expectations can threaten the legitimacy of a research project. Unfortunately, the perpetuation of expectations rarely occurs without hype and strong claims of an effect. Where there are expectations, a spatial dynamic is often created “whereby the further we travel from the source of knowledge production, the more colourful and flamboyant become the promissory properties of knowledge”
. This trend is consistent with previous work on the reporting of neuroscience research
[15, 27]. Our current data may well indicate the presence of such a spatial dynamic. In some germinal form, we saw that the primary authors’ description of their findings moved from memory retention in the results section to CE in the discussion. This trend was magnified in claims made in media and bioethics articles given their presentation of the results of the DFSS on two levels (specific and extended). Finally, when we consider the strong claims and latent expectations for CE found in our colloquialism and headline data, there is additional support for the hypothesis that there is a distinct trend to elaborate on findings, based on expectations rather than reflecting uncertainty, as claims are further removed from the source of the data.
The ethical challenges of hyped claims of CE effects for clinicians
One ethical implication of print media and bioethics literature hyping claims of CE effects while referencing primary research arises from the effect of hype on pre-existing expectations about CE drugs. Specifically, it has been widely recognized that one of the risks of endorsing the use of pharmaceuticals for enhancement purposes is that it may perpetuate social pressures, such as the pressure to perform, be productive, highly intelligent, or competitive
. Unchecked, social pressure may perpetuate social values that are not in line with the interests of the population as a whole, or do not reflect the interests of all individuals
. These performance-oriented values, though viewed by some as integral to a thriving society (e.g.
), may negatively impact individuals’ ideas of their own self-worth, fostering anxiety and discontent regarding genuinely lived experiences
, and subsequently inducing a society that instead celebrates those traits that are the most in line with quantifiable economic and military principles of productivity. The long-term social consequences of drug use for CE purposes are unknown; however, the risk of inducing a “medicated normality”, has been raised, where a loss of cultural and social diversity, accompanied by intolerance towards difference, would manifest as an assault on the autonomy of individuals
. Others have raised the possibility that such drug use could induce unanticipated changes to the complex biosocial and psychological functions of the brain, altering our social behaviour in an altogether different way
Research on the role of social pressure in the context of CE has isolated a “funnel phenomenon,”
 where social pressure covertly drives individual choice in the use of methylphenidate for CE among students
. When prompted, stakeholders in the debate (e.g., students, health care providers) firmly believed that students’ personal values guided their decision to use methylphenidate for CE (i.e., students acted autonomously). However, they also believed that social pressure to perform was so strong in the academic community that it created “a form of social determinism leading to conformity with social values through a concession of personal values”
. The authors concluded that personal values are an ornamental, rather than substantial, factor in decision-making. This finding has substantial implications in the context of our own results. If health care professionals believe individuals are making autonomous choices, yet external pressures are implicitly shaping these decisions, the task of determining whether an individual is being coerced to change a trait becomes challenging and worthy of attention from an ethics standpoint.
It has been recognized that as requests for “neuroenhancements” enter the clinical realm, physicians will be left with the difficult task of interpreting strong claims, modifying expectations, and addressing social pressure. However, recently published guidelines on how neurologists should deal with these requests
 concluded that neurologists were sufficiently aware of these social factors and thus left out specific recommendations on how to take social pressures into account, opting instead to support a physician-patient discussion
. As demonstrated by the previous data, there is a risk that within the context of the patient-physician relationship it will be difficult to determine whether the individual is in fact making informed decisions based on appropriate claims. Further, in its absence from the guidelines, the presumed importance of this issue may be overlooked. An extended patient-physician discussion may uncover reasons for the request; however, without specific guidelines to address misguided expectations and related social pressure in the clinical context, physicians may consider further attention to these issues unnecessary or even consider the presence of social pressure as an ethically justifiable reason to prescribe.
It has been suggested that the description of the lack of data on the safety and efficacy of cognitive enhancers would deter physicians from prescribing them
. However, as our study shows, this dearth of scientific evidence can be difficult to grapple with due to hyping of the results in media and bioethics literature. Indeed, these very guidelines cited the DFSS as evidence in support of the efficacy of these drugs
. Clearly, there is an important interaction between strong public claims about CE, pre-existing social pressure, the existence of expectations for CE, and the ability to adequately disseminate information on safety and efficacy. Mitigating misguided claims, social pressure, and expectations will be an ongoing process. Organizations have begun developing explicit recommendations on how to deal with social pressures surrounding CE agents
; however, more work is needed to help physicians integrate knowledge of social factors and circumstances that shape decision-making
. As the CE debate continues, caution should be further applied to avoid complicity with negative social norms that surround intellectual disability. Attention to disability ethics literature may help bioethicists and clinicians become acquainted with the obligations we have to support people with disabilities.
Another area to explore is how information could be provided to the public based not on single studies, but on more comprehensive and authoritative reviews of the literature. Primary researchers should consider means to reduce misappropriation of their work, and journalists and editors should be accountable for writing headlines that draw in readers while conserving accuracy.
In spite of broad searches and the use of multiple databases, our sample may not be exhaustive of all articles on non-medical use of donepezil with reference to the DFSS. The small sample size, which may well reflect the scope of the CE debate, makes it difficult to make any wide-reaching conclusions. Like other qualitative content and discourses analyses, though coding was double-checked and thoroughly pilot tested, controlling for subjectivity of data gathering and analysis is challenging and represents another study limitation. Further, our findings should not be interpreted as an accusation of the authors of the DFSS or of the specific journalists or scholars who were authors of the media and bioethics articles in our sample. We understand that the reported media statements reflect an amalgamation of data and opinions and do not necessarily reflect the opinions of the authors. Accordingly, the content of our sample should be viewed as a reflection of what members of the public have access to, rather than the individual voice of the author per se, and our findings should be considered a detailed exploration of the challenges of interpreting complex data and their contribution to contemporary ethics debates about neurological advances in healthcare and beyond.