Guilherme Azevedo -Audencia
email: gazevedo@audencia.com

INTO THE REALM OF ORGANIZATIONAL FOLLY: A POEM, A REVIEW, AND A TYPOLOGY OF ORGANIZATIONAL STUPIDITY

This 'Provocation essay' is aimed at triggering reflection and fostering renewed research into organizational stupidity and its intersections with management learning. It opens with a critical poem evoking diverse aspects of our daily encounters with the idiocy, nonsense, and absurdity that pervades organizations. It continues with a more comprehensive review of the still diffuse research literature to reveal a typology of three approaches to studying organizational stupidity (systemic-mechanistic, critical-sociological, and cultural-functionalist). It closes with a discussion of how stupidity detracts from reflexivity but can also play useful roles in organizations, which ultimately invites more management learning research on the topic.

Into the realm of organizational folly

Behind those walls stands a fine firm built by bright folks.

From out here, it seems all smart and neat but no hoax: its innards are plagued by nonsense, are obtuse baroques.

I enter with some silly questions: Please tell me, why all the merry-go-rounds? Discombobulations: Why so many rat races? Why such vain battlegrounds? I'm a befuddled scholar: Why the organizational stupidity that abounds? Oh, let thus my duty be to understand how that decent manager grew into a hypocrite; to discover how such great intelligence spawned pages devoid of wit; to unveil the business histories of their stockpiled bullshit.

Off I go, with good intentions and mixed methods, to do my erudite trickery. I look further, anew, and again at their laughable stocks of daily misery, muddling through trails of trials and tribulations, little hope of victory.

Indeed, there I encounter defunct creativity, for their frigid board members they must please; cadaverous futures, for short-sighted stockholders they must appease; decency that is no more, for always another penny they must squeeze.

I see dazed men and women who carry on with their senseless work. Too many mouths to feed, ends that must meet, mortgages that lurk.

Their souls hung out of sight. They no longer care about this cirque.

But if I contemplate further, underneath their wacky ways of today I find the heroic sagas of pioneers. Their mishmashes are the very scars of clever survival through the years.

Their weird morphology is but the archaeology of hard work, glory, and tears.

Through mazes of law and opaque cultural manners, they walk the feasible way. The tortuous paths, the murky talk, the impractical rituals keep insanity at bay. Their chicanery saves faces, their cynicism saves jobs, their folly saves the day! I then return to academic vanity.

Let the struggle with meandering sentences and vague ideas recommence. Messy data, hellish thick descriptions, scanty glimpses of dubious sense.

Wasteful writing and rambling thinking. My very profession a sad offence.

Back to my days of irrelevant contentment, my life of spoiled bookworm. Papers sink beneath the waves of oblivion, theories never to confirm.

And yet, behind those walls, there are bright folks building a fine firm.

-o-0-o-To put it simply, this Provocation essay is about organizational stupidity.

By addressing such a pedestrian matter, I wish to call attention to the hidden causes, unsuspected functions, and often dispiriting consequences of the collective idiocy, nonsense, and absurdity that pervades organizations. Despite being a source of trouble and waste to managers, employees, customers, and other stakeholders, this all-pervasive phenomenon remains surprisingly understudied.

Yet, better understanding it is particularly crucial to the management learning field [START_REF] Coraiola | From organizational learning to organizational mnemonics: Redrawing the boundaries of the field[END_REF] because, by disabling reflexivity [START_REF] Cunliffe | Reflexive dialogical practice in management learning[END_REF], organizational stupidity detracts organizations from accumulating knowledge and improving decision making. I thus review the still diffuse literature on the subject and contribute with a more comprehensive perspective, which includes a typology of three approaches to studying organizational stupidity. Concurring with the Management Learning vocation of publishing "unexpected, unconventional, unusual and unorthodox" pieces (Bell and Bridgman, 2018: 3), this poem-cum-commentary is ultimately aimed at using poetry and experimentation to "feed imagination, seed change and cultivate learning" (Brewis and Bell, 2020: 536).

The poem that opens this piece is a critical-perhaps jocose nonetheless-evocation of diverse aspects of organizational stupidity. Into the realm of organizational folly is a free-verse elegy written from the perspective of a management researcher. That is all I write about it here, for each reader should approach a piece of poetry with their own gaze. A more explicit explanation of the poem would thus be antithetical to the very nature of that medium. 1 Still, and in the spirit of writing differently [START_REF] Gilmore | Writing differently[END_REF], I take the liberty of playfully permeating this commentary with occasional fragments {within braces} extracted from the poem. These fragments should add a related, but not always obvious, connotation to the passage. By so doing, I wish to move beyond juxtaposing poetic and academic writing to also set points of contact where the two distinct voices can meet.

A closer look at organizational stupidity

In this commentary I address streams of literature built around the neighbouring concepts of organizational stupidity [START_REF] Mccomber | The organizational stupidity factor[END_REF][START_REF] Albrecht | Brain power: learn to develop your thinking skills[END_REF][START_REF] Kerfoot | Organizational intelligence/organizational stupidity: the leader's challenge[END_REF][START_REF] Alvesson | A stupidity-based theory of organizations[END_REF][START_REF] Paulsen | Slipping into functional stupidity: The bifocality of organizational compliance[END_REF]; incompetence [START_REF] Peter | The Peter principle[END_REF][START_REF] Ott | Toward a definition of organizational incompetence: a neglected variable in organization theory[END_REF][START_REF] Wagner | Smart people doing dumb things: the case of managerial incompetence[END_REF]; bullshit [START_REF] Allen | Bull markets and bull sessions[END_REF][START_REF] Spicer | Business bullshit[END_REF][START_REF] Christensen | Bullshit and organization studies[END_REF]; nonsense [START_REF] Azevedo | Does Organizational Nonsense Make Sense? Laughing and Learning from French Corporate Cultures[END_REF]; and absurdity [START_REF] Starkey | Management education and the theatre of the absurd[END_REF].

Those are typically critical texts that on occasion adopt a humorous twist and usually portray 1 Although rare, poetry can be a compelling medium to stimulate interrogations and to promote management research discussions. Poems published in management journals have provided critical, ironic, or emotional representations of issues that permeate and surround organizations [START_REF] Nutman | After they've gone[END_REF][START_REF] Saxton | The M&A game[END_REF][START_REF] Reid | Three poems on organisation, control and exchange[END_REF]. They can be autobiographical, offering humorous retrospectives of academic lives [START_REF] Inkson | The professor of management[END_REF] or more meditative ponderings about career turnarounds [START_REF] Hatch | Nostalgia for because[END_REF]. Poetry can be used to produce "alternative (non-mainstream) ways of looking at organization and management" (Kostera, 1997: 345). Moreover, as creativity invites creativity, management research poems have been written as hip-hop mashups [START_REF] Gartner | Entrepreneurship-hop[END_REF] or choir songs [START_REF] Inkson | The professor of management[END_REF] and have been supplemented with sketches and drawings [START_REF] Saxton | The M&A game[END_REF][START_REF] Inkson | The professor of management[END_REF]. organizational stupidity as ubiquitously observable in all fields of management research. {Organizations' innards are plagued by nonsense.} There is stupidity in public administration [START_REF] Mccomber | The organizational stupidity factor[END_REF][START_REF] Ott | Toward a definition of organizational incompetence: a neglected variable in organization theory[END_REF]; in financial services [START_REF] Allen | Bull markets and bull sessions[END_REF]; in nursing management [START_REF] Kerfoot | Organizational intelligence/organizational stupidity: the leader's challenge[END_REF]; in business education [START_REF] Bedeian | The dean's disease: How the darker side of power manifests itself in the office of dean[END_REF][START_REF] Olsen | The origin of the garbage can model theory[END_REF][START_REF] Starkey | Management education and the theatre of the absurd[END_REF]; in organizational cultures [START_REF] Azevedo | Does Organizational Nonsense Make Sense? Laughing and Learning from French Corporate Cultures[END_REF]; and in management communication [START_REF] Spicer | Business bullshit[END_REF]. I begin by acknowledging some antecedents of extant literatures that address stupidity in organizations. That is followed by a proposed conceptual terrain for organizational stupidity research. I then put forward a typology of three major approaches to studying it before concluding with a short discussion.

Some antecedents of present-day organizational stupidity research

Arguably, organizational stupidity research was founded by a few publications up to six decades ago [START_REF] Parkinson | Parkinson's Law[END_REF][START_REF] Peter | The Peter principle[END_REF][START_REF] Mccomber | The organizational stupidity factor[END_REF] before eventually regaining some vigour over the last decade [START_REF] Alvesson | A stupidity-based theory of organizations[END_REF][START_REF] Paulsen | Slipping into functional stupidity: The bifocality of organizational compliance[END_REF][START_REF] Spicer | Business bullshit[END_REF][START_REF] Christensen | Bullshit and organization studies[END_REF][START_REF] Starkey | Management education and the theatre of the absurd[END_REF][START_REF] Azevedo | Does Organizational Nonsense Make Sense? Laughing and Learning from French Corporate Cultures[END_REF]. On the one hand, organizational stupidity constitutes a phenomenon that should be as old as organizations themselves. On the other hand, some argue that bullshit and absurdity {laughable stocks of daily misery} have become more prevalent in recent times (Frankfurt, 2005;[START_REF] Foley | The age of absurdity: Why modern life makes it hard to be happy[END_REF], in an age of kakistocracy with many societies being ruled by the worst possible leaders (Mohammed, 2020: 246).

The etymology of stupidity comes from the Latin noun stupiditatem [dullness, folly, or senselessness], derived from the adjective stupidus [dull, foolish, or confounded]. Stupid people are hence those who are slow of mind, lacking intelligence or reason, or given to unintelligent decisions or acts [START_REF] Merriam-Webster | Merriam-Webster online dictionary[END_REF]. When working together they are likely to create stupid organizations; but a distinctive feature of collective stupidity is that a gathering of intelligent individuals can add up to be collectively stupid. {Great intelligence spawning pages devoid of wit.}

As enunciated in what became known as Albrecht's Law:

Intelligent people who can think and act very effectively as individuals can, as a group, exhibit the most profoundly stupid and counterproductive responses to the demands of their environment. (Albrecht, 1980: 236) Pioneering texts have tried to explain the stupidity bourgeoning in organizations, particularly in bureaucracies, by describing mechanisms articulated as laws or principles. Those notably include Cyril N. Parkinson's enunciation of Parkinson's Law, postulating that "work expands so as to fill the time available for its completion" [START_REF] Parkinson | Parkinson's Law[END_REF][START_REF] Parkinson | Parkinson's Law, and other studies in administration[END_REF], and Laurence J. Peter's formalization of the Peter Principle, stating that "in a hierarchy, every employee tends to rise to his level of incompetence" [START_REF] Peter | The Peter principle[END_REF]. More recently, in what became known as the Dunning-Kruger effect, it has been shown that incompetent people tend to underestimate their own incompetency, whereas those who are more competent tend to be more aware of their limitations (Dunning and [START_REF] Kruger | Unskilled and unaware of it: How difficulties in recognizing one's own incompetence lead to inflated self-assessments[END_REF].

The existing research on organizational dysfunctionalities is evidently much broader than the attempt to describe problematic aspects of organizations as laws and principles named after their proponents. Indeed, some foundations of organizational theory rest upon seminal research on bounded rationality [START_REF] Simon | A behavioral model of rational choice[END_REF][START_REF] March | Organizations[END_REF] and upon studies of flawed decisions with catastrophic consequences for working teams (e.g., the death of firefighters who did not drop their heavy tools [START_REF] Weick | The Collapse of Sensemaking in Organizations: The Mann Gulch Disaster[END_REF]) or to entire organizations (e.g., deviant decisions at NASA that caused the Challenger space shuttle disaster [START_REF] Vaughan | The Challenger launch decision: risky technology, culture, and deviance at NASA[END_REF]). I argue nevertheless that, despite providing crucial explanations of decision failures, those studies do not fully characterize organizational stupidity research. It could be disputed that limited rationality and bad decision making are by definition stupid, but the assessment of the literature reveals that organizational stupidity research tends to look at more pathologically pervasive dysfunctionalities than just at precise instances of decision failures (Ott and Shafritz, 1994: 372-373).

Organizational stupidity hence refers to the systemic collective stupidity that can potentially permeate entire organizations [START_REF] Peter | The Peter principle[END_REF][START_REF] Kerfoot | Organizational intelligence/organizational stupidity: the leader's challenge[END_REF][START_REF] Paulsen | Slipping into functional stupidity: The bifocality of organizational compliance[END_REF]. {All the merrygo-rounds, so many rat races, such vain battlegrounds.} For instance-and referring again to a seminal text-Parkinson described, over half a century ago, organizations suffering from injelititis, a pathology caused by the rise to authority of individuals with unusually high injelitance (i.e., the combination of incompetence and jealousy):

We find everywhere a type of organization […] in which the higher officials are plodding and dull, those less senior are active only in intrigue against each other, and the junior men are frustrated or frivolous. Little is being attempted. Nothing is being achieved. (Parkinson 1957: 78) {Defunct creativity, cadaverous futures.} Widespread organizational stupidity can indeed-as discussed in more detail later in this essay-be rooted in systems, in collective behaviour, and in organizational cultures. First, however, it may be useful to shed some light on how the notion of organizational stupidity relates to-and often becomes entangled with-some of its neighbouring concepts.

Mapping the terrain of organizational stupidity research

Organizational stupidity can be conflated with other concepts, notably organizational incompetence, bullshit, nonsense, and absurdity. To outline the scope of organizational stupidity research, it is hence useful to map a specific terrain (Brewis and Bell, 2020: 535) by better understanding how those concepts relate to each other.

Organizational incompetence, which can be defined as the "repeated pattern of an organization not able or willing to learn from its environment, its failures, or its successes" (Ott and Shafritz, 1994: 370), is a quasi-synonym of organizational stupidity, possibly with two minor semantic distinctions.

First, incompetence carries the somewhat more procedural or less derogatory connotation of lack of competence [START_REF] Peter | The Peter principle[END_REF]. Second, incompetence (as the lack of qualities needed for effective action [START_REF] Merriam-Webster | Merriam-Webster online dictionary[END_REF]) tends to be perceived as more likely to be remediated through organizational redesign [START_REF] Peter | The Peter principle[END_REF] and through the acquisition of organizational knowledge, typically by training or hiring [START_REF] Ott | Toward a definition of organizational incompetence: a neglected variable in organization theory[END_REF].

Bullshit can be defined as a colloquial or vulgar noun for nonsense or foolish insolent talk [START_REF] Merriam-Webster | Merriam-Webster online dictionary[END_REF]. It refers more often to what is said {the murky talk}, whereas stupidity and incompetence refer more often to what is done. Moreover, although both organizational stupidity and bullshit result in time and resources being wasted, organizational bullshit is occasionally recognized as having social functions and as related to specific managerial practices [START_REF] Christensen | Bullshit and organization studies[END_REF]. Organizational bullshit has recently attracted substantial attention from both academics and practitioners, and research on the topic is becoming more sophisticated. Although initial studies addressed mostly the harmful consequences of bullshit (Frankfurt, 2005) and proposed agendas for minimizing the production and exchange of business bullshit (Spencer, 2017), the focus of bullshit research has gradually turned to its performative functions and to the interactions between those involved in its transactions, namely the bullshitter and the bullshittee [START_REF] Allen | Bull markets and bull sessions[END_REF][START_REF] Christensen | Bullshit and organization studies[END_REF].

Management research built upon the concepts of organizational nonsense [START_REF] Azevedo | Does Organizational Nonsense Make Sense? Laughing and Learning from French Corporate Cultures[END_REF] and absurdity [START_REF] Starkey | Management education and the theatre of the absurd[END_REF] remains extremely rare. Those terms tend to refer to aspects of organizational life that pose a challenge to organizational members and researchers by being "apparently absurd or contrary to good sense" (Azevedo, 2020: 385). {Wacky ways; tortuous paths.} Consequently, they often invite the reader to "reflect on the human condition and on our current business and social context" (Starkey, Tempest, and Cinque, 2019: 592-593). Organizational stupidity and incompetence are hence more often depicted as inherent to the organization, whereas texts on organizational bullshit, nonsense, and absurdity tend to adopt a more subjectivist perspective. There is, for instance, no clear agreement on what constitutes organizational bullshit [START_REF] Spicer | Business bullshit[END_REF], and it is potentially possible to make sense of what appears to be nonsensical or absurd [START_REF] Azevedo | Does Organizational Nonsense Make Sense? Laughing and Learning from French Corporate Cultures[END_REF]. In other words, organizational stupidity and incompetence are often perceived as belonging to the organization, whereas organizational bullshit, nonsense, and absurdity can also be in the eye of the beholder.

Finally, organizational bullshit is also portrayed as a communication practice "intentionally designed to bear no relationship to truth by purposefully obscuring organizational function and reality" (Mohammed, 2020: 244). {Meandering sentences and vague ideas.} Therefore, although it may at first glance appear just stupid, organizational bullshit is often created and maintained by design (Spicer, 2018: xii). It means that some talented organizational members can purposefully build an architecture of bullshit to serve their interests. That perspective contrasts with the typical understanding that organizational absurdity, stupidity, and incompetence emerge as the unplanned, almost organic accumulation of idiosyncrasies. In that regard, organizational nonsense arguably occupies an intermediate position because it can be both the result of idiosyncratic occurrences and of intentional actions by agents [START_REF] Azevedo | Does Organizational Nonsense Make Sense? Laughing and Learning from French Corporate Cultures[END_REF]. This effort to delineate a research terrain for organizational stupidity sheds some light on the relationships between concepts that occasionally overlap and get conflated. I hence acknowledge the extant uncertainty [START_REF] Brewis | Provocation essays editorial: On the importance of moving and being moved[END_REF] 533) of organizational stupidity conceptualizations but, nonetheless, I refrain from either selecting or proposing a precise definition. Rather, I examine the emergence of a possible management learning literature that comprises a range of views of stupidity in organizations and that also encompasses other organizational attributes deemed dysfunctional. Thus, by treating organizational stupidity in broader terms, I also survey the research literature that addresses organizational incompetence, bullshit, nonsense, and absurdity.

A typology of approaches to studying organizational stupidity

Various are the ways of approaching the stupidity that exists in organizations. My effort to build a more comprehensive perspective reveals, in particular, the existence of three major ways to study organizational stupidity and its neighbouring concepts. Each approach has specific consequences for the management learning field and, together, they form a typology that can help us to assess and examine the organizational stupidity phenomenon in a more structured manner.

A systemic-mechanistic approach In this approach, organizations are perceived as systems that contain flaws to be corrected. {Obtuse baroques; weird morphologies.} As in a systems theory view, organizational stupidity constitutes sub-optimal equilibria of systems which management should correct by reconfiguring their organizations. The systemic-mechanistic approach often enunciates normative directions for improving organizations by making changes to organizational structure, leadership style, and knowledge management: Stupid organizations will flourish unless the knowledge and experience of all within the organization are harnessed effectively. […] Without structures such as shared leadership and other forms of participative management, the organization or unit cannot access and use the available information and wisdom in the organization. (Kerfoot, 2003: 92) Under this approach, organizations are analogous to mechanisms where inadequate outcomes are due to deficient design or lack of resources. Some studies may even equate organizational stupidity with lack of technology as, for instance, in McComber and Jenkins's early proposition of an "organizational stupidity factor":

The rate at which an organization falls behind technology and becomes less able to compete may be called the "Organizational Stupidity Factor" since it represents the rate at which the organization will make stupid decisions. (McComber and Jenkins, 1972: 46) Alternatively, if the scarce resource is knowledge, the organization will suffer from a collective form of ignorance, hence being prone to making bad decisions (Roberts, 2012). Therefore, although tending to have a less negative connotation, ignorance (i.e., lack of knowledge, or not knowing something) is a major cause of stupidity. This unveils a fundamental relation between organizational stupidity and ignorance, both crucial concepts to the management learning field (Coraiola and Murcia, 2020: 236).

Moreover-and complementing Albrecht's Law-under the systemic-mechanistic approach intelligent individuals become collectively stupid because they are in the grip of bad systems.

Considerations given to systems have priority over those directed at individuals because, as in Pfeffer and Sutton's (2006: 102) "law of crappy systems trumps the law of crappy people:" "bad systems do far more damage than bad people, and a bad system can make a genius look like an idiot." Thus, organizations may become systems that encourage intelligent people to act stupidly: "Organisations hire smart people, but then positively encourage them not to use their intelligence [and those] who learn how to switch off their brains are rewarded" [START_REF] Spicer | Stupefied: how organisations enshrine collective stupidity and employees are rewarded for checking their brains at the office door[END_REF].

That approach has a straightforward, if not simplistic, relationship with management learning: an organization will be better equipped to learn if it adopts suitable technology, organizational structures, leadership methods, and knowledge management. Studies adopting a systemicmechanistic approach are still being conducted, but that view tends {as heroic sagas of pioneers} to predate the other two. Interestingly though, despite being built mostly upon early studies of bureaucracies-or perhaps because of that-this approach leans toward proposing solutions that focus on formal aspects of organizations (e.g., structure, technology, and managerial methods). The underlying assumption is that human behaviour and choice can be observed through a prism of rationality [START_REF] Simon | A behavioral model of rational choice[END_REF]; and, therefore, these studies tend not to take notice of the collective stupidity that emanates from the human interactions that create and operate systems.

A fundamental limitation of this approach is thus that, by ignoring human factors, it proposes solutions that can actually be unworkable. For instance, one of its fundamental tenets is that managers must redesign their organizations with better systems to reduce organizational stupidity.

Such redesign efforts would be particularly profitable because the organization would gain productivity by being less stupid. That poses a perverse conundrum, however: reducing stupidity would be a smart move, but stupid organizations are systems that encourage managers not to use their intelligence.

A critical-sociological approach

The second approach describes and often denounces organizational stupidity as a perverse consequence of combined sociological and institutional factors. Although more sophisticated sociological frames are adopted to explain it, this approach basically agrees with Albrecht's view that organizational stupidity is "an inevitable part of all large human endeavors" (1980: 268). {Trails of trials and tribulations, little hope of victory.} Organizational stupidity can thus can be reduced, but never eradicated. In the systemic-mechanistic approach, the antidote to organizational stupidity is to design better systems, whereas here the palliative remedy is to promote organizational learning, reflexivity, and critical-thinking capabilities. Indeed, in this approach, organizational stupidity can be defined as the "refusal to use critical thinking" (Starkey, Tempest, and Cinque, 2019: 595). In their critique, Kenneth Starkey and co-authors denounce management and management education as too often being exercises in rhinoceritis, a concept of dysfunctional group thinking adapted from Ionesco's views on absurdity: rhinoceritis is "a pernicious and pervasive tendency to conformity that leads to an inability to think critically about the state we are in" (Starkey, et al., 2019: 592).

Organizations thus become the worsened portrait of their creators, i.e., human beings who are imperfect, incapable of full rationality, and sometimes animated by egoism and by lack of respect for others. The critical-sociological approach responds to the previous one by taking human nature into account. It typically combines sociological stances and critical perspectives to explain how human interactions produce organizational stupidity. Such views are often closely related to issues of lack of reflexivity [START_REF] Cunliffe | Reflexive dialogical practice in management learning[END_REF] and to organizational learning deficiencies, which are recurrent concerns for the Management Learning community [START_REF] Anderson | Reviewing Management Learning: The field and the journal[END_REF]. In some instances, this approach can be aimed at identifying and exposing the spurious moral origins and consequences of the stupidity that permeates organizations {decency that is no more}, which fits an agenda that is typical of critical management studies.

Overall, by recognizing that collective stupidity is rooted in human interactions, this approach can portray individuals as both the victims of the oppression caused by organizational stupidity and as the source of the moral flaws that create it. On the one hand, organizations can do stupid things despite their members' and leaders' intelligence, good intentions, and dedication. Learning from perspectives of bounded rationality and of flawed collective decision making, studies adopting a critical-sociological approach can disclose unforeseen dysfunctional consequences of how people learn, communicate, and act, with the blame usually assigned to decision processes turned chaotic [START_REF] Cohen | A garbage can model of organizational choice[END_REF]; to underlying psychological dispositions causing teamwork failure [START_REF] Weick | The Collapse of Sensemaking in Organizations: The Mann Gulch Disaster[END_REF]; and to gradual deviation of behaviour due to work complexity and pressure [START_REF] Vaughan | The dark side of organizations[END_REF]. On the other hand, some studies in this approach also emphasize the moral imperfection of individuals that, if raised to positions of influence, will contribute to the erosion of the collective moral constitution, thereby making the entire organization degenerate and stupid. {Decent managers growing into hypocrites.} Those texts are typically devoted to revealing the dark side of organizations [START_REF] Vaughan | The dark side of organizations[END_REF][START_REF] Bedeian | The dean's disease: How the darker side of power manifests itself in the office of dean[END_REF]; to explaining how industries and organizations may slip into moral decrepitude [START_REF] Jackall | Moral mazes: the world of corporate managers[END_REF]; and decrying the process whereby leaders may be blinded by "power, prestige, and performance [that make them] stubborn, stupid, and resistant to valid evidence" (Pfeffer and Sutton, 2006: 225;[START_REF] Bedeian | The dean's disease: How the darker side of power manifests itself in the office of dean[END_REF].

Interestingly, when probing into the sociological and moral complexities of organizations that eventually act stupidly, scholars find abundant inspiration in their own academic institutions [START_REF] Bedeian | The dean's disease: How the darker side of power manifests itself in the office of dean[END_REF][START_REF] Wagner | Smart people doing dumb things: the case of managerial incompetence[END_REF][START_REF] Olsen | The origin of the garbage can model theory[END_REF][START_REF] Starkey | Management education and the theatre of the absurd[END_REF]. {My very profession a sad offence.} That may be illustrated by two notable cases related to the recruitment and leadership styles of deans. The first was told by Johan P. [START_REF] Olsen | The origin of the garbage can model theory[END_REF]. He explained in an interview that the fortuitous observation of an academic institution hiring its new dean provided him and his co-authors with the inspiration for their very influential garbage can model of choice [START_REF] Cohen | A garbage can model of organizational choice[END_REF]. The dean search they observed evolved in a chaotic manner, basically due to the random availability of those in charge of the collective decision. It ended with none of the potential candidates being selected. {Discombobulations.} The second case was presented by Arthur G. [START_REF] Bedeian | The dean's disease: How the darker side of power manifests itself in the office of dean[END_REF] as the dean's disease to illustrate how the moral deficiencies of a leader can contribute to making an entire organization stupid. He borrowed from some organizational stupidity classics, such as [START_REF] Parkinson | Parkinson's Law, and other studies in administration[END_REF] injelitance concept (see also [START_REF] Brimelow | How do you cure injelitance?[END_REF], to denounce the manifestation of "the darker side of power" in deans' offices:

[There are cases] where deans have doubts about their own competence and are jealous of anyone seen as more able or prominent. In such instances, [… deans] surround themselves with acolytes who are nonthreatening, so as to protect their ego and position. [START_REF] Parkinson | Parkinson's Law, and other studies in administration[END_REF] has justly labeled this phenomenon 'injelitance,' defined as a form of organizational paralysis compounded equally of incompetence and jealousy. (Bedeian, 2002: 167) In summation, this approach identifies the sociological origins of organizational stupidity, denounces the moral flaws of organizational members, and exposes their perverse consequences. The implicit solution it offers to organizational stupidity is to reinforce the individual and collective capacities of communicating, learning, and, more importantly, to reflect critically on the possible flaws of their organizations. However, even if considering that the eradication of organizational stupidity is a quixotic fight because it is rooted in the very nature of human interactions, both this approach and the previous one implicitly assume that organizational stupidity is inherently bad and should be tackled.

A cultural-functionalist approach

Beyond the idea that stupidity can be culturally induced (Alvesson and Spicer, 2016: ch. 8) and the explicit sense of people "act[ing] stupidly out of a desire to adhere to cultural norms" (Ott and Shafritz, 1994: 375), the third approach suggests that an organizational feature that seems dysfunctional, but that endures over time, probably exists because it fulfils a function. It drops the assumption of organizational stupidity as being dysfunctional or perverse to adopt instead a more subjectivist perspective, which, as argued earlier, is an attribute more often assigned to organizational bullshit, nonsense, and absurdity than to organizational stupidity and incompetence. In the cultural-functionalist approach, the perceived organizational pathology can be in the eye of the beholder (Ott and Shafritz, 1994: 373). Organizational stupidity "may provide certainty, regularity, and may be functional to maintaining organizational order" (Coraiola and Murcia, 2020: 235, emphasis in original). Therefore, stupidity can have a reason for being. {Opaque cultural manners; they walk the feasible way.} For instance, a language deemed bullshit because it lacks meaning and is inflated with grandiose claims can be simply the result of a genuine attempt to think and communicate better:

[We] have in mind a productive sort of bullshit: bullshit that ultimately produces better thought and better selves. We must acknowledge that benign bullshit is inevitable when people are attempting to write well. (Eubanks and Schaeffer, 2008: 387) Some of these studies openly adhere to a culturalist view of the firm [START_REF] Schein | Organizational culture and leadership[END_REF] and are even explicitly aimed at developing "a better understanding of possible origins, functions, and consequences of traits of organizational cultures perceived as nonsensical" (Azevedo, 2020: 398).

More often, however, they simply build upon the assumption that organizational features potentially deemed stupid, bullshit, nonsensical, or absurd can have useful functions (Allen, Allen, and McGoun, 2012: 26). For instance, organizational bullshit can serve managers when they command or strategize [START_REF] Christensen | Bullshit and organization studies[END_REF]: 1593-1595); functional stupidity allows workers to "not ask critical questions" (Paulsen, 2017: 200); and there is an ever-growing repertoire of otherwise pointless tasks that are useful for filling the work hours of those stuck in bullshit jobs [START_REF] Graeber | On the phenomenon of bullshit jobs: a work rant[END_REF][START_REF] Graeber | Bullshit jobs: a theory[END_REF][START_REF] Glaser | Beyond bullshit jobs[END_REF]. {Cynicism saves jobs.} There are thus many reasons for people in organizations to decide not to learn (Coraiola and Murcia, 2020: 235-236), and stupidity can fulfil various functions in organizations:

[Functional stupidity] can save the organization and its members from the frictions provoked by doubt and reflection. Functional stupidity contributes to maintaining and strengthening organizational order. It can also motivate people, help them to cultivate their careers, and subordinate them to socially acceptable forms of management and leadership. (Alvesson andSpicer, 2012: 1196) This approach tends to adopt a particularism stance by perceiving organizational stupidity as context specific. The reasons why workers end up "not thinking too much" cannot be generalized across workplaces (Paulsen, 2017: 200) and apparently trivial considerations such as "why smart executives fail" may require the analysis of specific histories of companies to disclose particular patterns of managerial behaviour [START_REF] Finkelstein | Why smart executives fail: four case histories of how people learn the wrong lessons from history[END_REF]. {Business histories of stockpiled bullshit.} The surrounding cultural context also matters. For instance, the apparent nonsense of a French corporation's director spending a long time describing a little-known passage of a philosopher's life {erudite trickery} may fulfil the crucial function of reinforcing his legitimacy with a "necessary demonstration of erudition" (Azevedo, 2020: 394).

For the cultural-functionalist approach, the "important task is to understand more about what it is and what role it plays in organizations" [START_REF] Christensen | Bullshit and organization studies[END_REF]Rasche, 2019: 1593). {Underneath their wacky ways.} The effort to disclose those roles can take the form, for instance, of business history research of past managerial failures [START_REF] Finkelstein | Why smart executives fail: four case histories of how people learn the wrong lessons from history[END_REF]; of cultural interpretations aimed at making sense of corporate cultures' nonsensical traits [START_REF] Azevedo | Does Organizational Nonsense Make Sense? Laughing and Learning from French Corporate Cultures[END_REF]; or of ethnographic research about the "rationales of stupidity" that motivate workers to carry on with the work they know is stupid (Paulsen, 2017: 200-204). The search for the hidden functions of what is apparently stupid also profits from the work done in other disciplines, which reveal, for instance (in sociology, communication, and education studies, respectively): that ignorance can be a productive asset to individuals and organizations [START_REF] Mcgoey | The logic of strategic ignorance[END_REF]; that ambiguity can play an important role in organizational communication [START_REF] Eisenberg | Ambiguity as strategy in organizational communication[END_REF]; and that bullshit can become a form of resistance [START_REF] Gaztambide-Fernández | Bullshit as resistance: justifying unearned privilege among students at an elite boarding school[END_REF].

The intersection with the management learning field is perhaps more subtle but very promising: a closer investigation of organizational stupidity can reveal some unsuspected limits to the promotion of organizational learning. In some instances, or beyond a certain level, learning and reflexivity become detrimental and counterproductive. Occasionally, to progress in a job or to preserve an organization, it is better not to act intelligently [START_REF] Spicer | Stupefied: how organisations enshrine collective stupidity and employees are rewarded for checking their brains at the office door[END_REF], not to think too much [START_REF] Paulsen | Slipping into functional stupidity: The bifocality of organizational compliance[END_REF], and even to make a strategic use of ignorance [START_REF] Mcgoey | The logic of strategic ignorance[END_REF]. {Their chicanery saves faces; their folly saves the day.} There is, therefore, a time and place for reflexivity in organizations but also a time and a place for avoiding it.

Finally, in contrast to the previous two, the third approach refrains from making objective judgments about the quality or morality of organizations. Instead, it tends to adopt a Boasian cultural relativism perspective and to assume that the functions of what is apparently stupid can only be revealed if one understands the organization's specific features and ways of functioning. {Impractical rituals keep insanity at bay.} That unveils a particularly problematic aspect of the cultural-functionalist approach: its primary interest is neither to correct the organizational stupidity (as in the first one) nor to mitigate it (as in the second one), but just to understand, appreciate, and, possibly, find better ways to accept and live with it.

Three complementary understandings

The main aspects of the approaches composing the typology I describe are presented in Table 1. It can be noted that most of our views on stupidity in the field of management learning have surpassed a systemic-mechanistic approach to embrace a more typically critical-sociological one. However, it has only been very recently that we have evoked the possible functional role of stupidity (Coraiola and Murcia, 2020: 235-236).

---Insert Table 1 about here ---Overall, the typology shows that we already rely upon complementary perspectives to explain specific instances of organizational stupidity. For the sake of illustrating how they produce distinct explanations, I revisit here how the literature tries to make sense of the creation of useless jobs by organizations. Early references perceived the issue mostly through a systemic-mechanistic approach:

Granted that work (and especially paper work) is thus elastic in its demands on time, it is manifest that there need be little or no relationship between the work to be done and the size of the staff to which it may be assigned. (Parkinson, 1955: 1) That phenomenon has recently regained attention, especially since David Graeber (2013)2 popularized the concept of bullshit jobs and argued that "at least half of all work being done in our society could be eliminated without making any real difference at all" (Graeber, 2018: 26). {Dazed men and women who carry on with their senseless work.} His proposition is more closely affiliated to the critical-sociological approach in that it criticizes current economic models and questions how human interactions eventually contribute to preserving worthless jobs:

[A] bullshit job is a form of paid employment that is so completely pointless, unnecessary, or pernicious that even the employee cannot justify its existence even though, as part of the conditions of employment, the employee feels obliged to pretend that this is not the case. (Graeber, 2018: 9-10) Finally, a cultural-functionalist approach could probe the possible hidden functions of pointless jobs existing in capitalist societies that should promote efficiency. A key to deciphering this apparent conundrum resides in the assumption that "it doesn't matter if those jobs do something useful; we just assume that more jobs is better no matter what" (Graeber, quoted in Illing, 2019). That underlying cultural assumption [START_REF] Schein | Organizational culture and leadership[END_REF] does indeed reflect an entrenched ambiguity of an economic model that combines a neoliberal discourse of austerity and an obsession with economic growth that requires the permanent creation of jobs [START_REF] Glaser | Beyond bullshit jobs[END_REF]. Therefore, by delineating three approaches for addressing organizational stupidity, the typology allows us to advance toward a more complete understanding of the phenomenon even if, as with the proverbial blind men describing an elephant, the full picture can still elude us.

Conclusion

Organizational learning-the most frequent theme of study in Management Learning (Anderson et al., 2020: 23)-is hindered by the extant collective stupidity that compromises reflexivity, knowledge gathering, and better decision making. To open up the "existing ways of thinking about knowledge and learning to critical scrutiny" (Bell and Bridgman, 2018: 3) in this Provocation essay, I examined the emergence of literature streams addressing organizational stupidity and neighboring conceptualizations. I began by identifying some antecedents to current perspectives, then delimited a terrain for research on organizational stupidity and identified intersections with the management learning field. Taking stock of the existing research on the topic, I contributed a more comprehensive perspective and proposed a typology of three approaches to studying organizational stupidity.

We know-often from painful experience-that stupidity, incompetence, bullshit, nonsense, and absurdity are ubiquitous organizational phenomena, but we still need to understand why they are so abundant and persistent. {I'm a befuddled scholar: Why the organizational stupidity that abounds?} Although the literature review indicates that research on the topic remains theoretically underdeveloped, some important preliminary efforts have been made. More importantly, this essay points to some specific intersections between stupidity and organizational learning that, I argue, deserve further investigation. There is a vast world of mysterious, unexamined stupidity out there, and it would be silly not to put some effort into better understanding it.

Future research could investigate the performative functions of organizational stupidity and the ways it may serve individual and collective interests. Instead of aiming at its unachievable eradication, management learning scholars should learn about stupidity and investigate, for instance, how its gradual acquisition allows individuals to advance and companies to prosper. Growing research evidence shows that, contrary to what we may suppose, certain organizational objectives can only be reached by being stupid [START_REF] Allen | Bull markets and bull sessions[END_REF][START_REF] Paulsen | Slipping into functional stupidity: The bifocality of organizational compliance[END_REF][START_REF] Christensen | Bullshit and organization studies[END_REF]. That is perhaps a disturbing finding for management learning scholars, but a serious look at how stupidity flourishes and thrives in organizations indicates that learning and reflexivity can on occasion be detrimental to individual careers and businesses as a whole. Our incursion into the realm of organizational folly thus warns us that too much of a good thing can be bad. Overall, it also suggests that our research effort to understand organizational learning must be matched by the attempt to also understand how organizations unlearn, forget, and, on occasion, act stupidly. Therefore, I call for more vigorous research into the unsuspected causes and functions of aspects of organizational life that tend to remain unexamined because they are dismissed as mere stupidity.

Finally, {return to academic vanity} I insist that studying stupidity is urgent not only because it permeates the organizations we study but also because it pervades the very work we do as scholars.

Indeed, academic writing is flooded with bullshit language [START_REF] Eubanks | A kind word for bullshit: The problem of academic writing[END_REF]; a considerable share of the tasks we perform resemble those of bullshit jobs [START_REF] Graeber | On the phenomenon of bullshit jobs: a work rant[END_REF][START_REF] Graeber | Bullshit jobs: a theory[END_REF]; and absurdity flourishes with splendorous vitality in management research and education [START_REF] Starkey | Management education and the theatre of the absurd[END_REF]. I hence hope that this Provocation essay encourages us, as management researchers, to reflect more carefully on and to debate more openly all the organizational stupidity and evident ridiculousness that surrounds us. {Papers sink beneath the waves of oblivion, theories never to confirm.} Which brings me back to poetry, to self-irony, and how this commentary began:

My research was so irrela-vent, That they made me an associate prof of management.

[…] And if managing nothing, your lives are spent, Then you all may be professors of management! (Kerr [START_REF] Inkson | The professor of management[END_REF] The professor of management)

Sadly, the composition of this essay coincided with the passing away (on September 2, 2020) of the American anthropologist and anarchist activist David Graeber.


Vincent Cottin
email: vincent.cottin@chu-lyon.fr

Fernando J Martinez

R Gisli Jenkins

John A Belperio

Hideya Kitamura

Maria Molina-Molina

Inga Tschoepe

Carl Coeck

Dirk Lievens

Ulrich Costabel

R Gisli Jenkins

Safety and tolerability of nintedanib in patients with progressive fibrosing interstitial lung diseases: data from the randomized controlled INBUILD trial

Keywords: Adverse drug event, Clinical trial, Diarrhea, Patient adherence, Pulmonary fibrosis Graphical

ou non, émanant des établissements d'enseignement et de recherche français ou étrangers, des laboratoires publics ou privés.

Background

In addition to all patients with idiopathic pulmonary fibrosis (IPF), a proportion of patients with other chronic fibrosing interstitial lung diseases (ILDs) develop a progressive fibrosing phenotype characterized by increasing fibrosis on high resolution computed tomography (HRCT); worsening of lung function, symptoms and quality of life; and early mortality [START_REF] Wells | What's in a name? That which we call IPF, by any other name would act the same[END_REF][START_REF] Brown | The natural history of progressive fibrosing interstitial lung diseases[END_REF][START_REF] Faverio | Progressive fibrosing interstitial lung diseases: prevalence and characterization in two Italian referral centers[END_REF][START_REF] Nasser | Progressive fibrosing interstitial lung disease: a clinical cohort (the PROGRESS study)[END_REF].

Nintedanib is an intracellular inhibitor of tyrosine kinases that inhibits processes fundamental to the progression of pulmonary fibrosis [START_REF] Wollin | Mode of action of nintedanib in the treatment of idiopathic pulmonary fibrosis[END_REF][START_REF] Wollin | Potential of nintedanib in treatment of progressive fibrosing interstitial lung diseases[END_REF]. Randomized placebo-controlled trials have demonstrated that nintedanib slows the progression of ILD in patients with IPF [START_REF] Richeldi | Efficacy and safety of nintedanib in idiopathic pulmonary fibrosis[END_REF], systemic sclerosis-associated ILD (SSc-ILD) [START_REF] Distler | Nintedanib for systemic sclerosis-associated interstitial lung disease[END_REF], and progressive fibrosing ILDs other than IPF [START_REF] Flaherty | Nintedanib in progressive fibrosing interstitial lung diseases[END_REF]. The adverse event profile of nintedanib in patients with ILDs is characterized mainly by gastrointestinal adverse events, particularly diarrhea [START_REF] Richeldi | Efficacy and safety of nintedanib in idiopathic pulmonary fibrosis[END_REF][START_REF] Distler | Nintedanib for systemic sclerosis-associated interstitial lung disease[END_REF][START_REF] Flaherty | Nintedanib in progressive fibrosing interstitial lung diseases[END_REF][START_REF] Corte | Safety, tolerability and appropriate use of nintedanib in patients with idiopathic pulmonary fibrosis[END_REF][START_REF] Lasky | Safety of nintedanib in patients with idiopathic pulmonary fibrosis: global pharmacovigilance data[END_REF][START_REF] Seibold | Safety and tolerability of nintedanib in patients with systemic sclerosis-associated interstitial lung disease: data from the SENSCIS trial[END_REF][START_REF] Flaherty | Nintedanib in progressive interstitial lung diseases: data from the whole INBUILD trial[END_REF].

The INBUILD trial was conducted in patients with chronic fibrosing ILDs other than IPF that had progressed within the prior 24 months despite management deemed appropriate in clinical practice [START_REF] Flaherty | Nintedanib in progressive fibrosing interstitial lung diseases[END_REF]. The trial population included patients with a variety of diagnoses who were taking a wide range of comedications [START_REF] Flaherty | Nintedanib in progressive fibrosing interstitial lung diseases[END_REF][START_REF] Cottin | Nintedanib and immunomodulatory therapies in progressive fibrosing interstitial lung diseases[END_REF]. The primary endpoint of the annual rate of decline in forced vital capacity (FVC) was assessed over 52 weeks; however patients continued to receive blinded randomized treatment until the last patient had completed the trial, so most patients received trial medication for longer than 52 weeks. We used data from the whole INBUILD trial to perform a comprehensive analysis of the safety and tolerability of nintedanib in this patient population.

Methods

Trial design

The design of the INBUILD trial has been published, together with the trial protocol [START_REF] Flaherty | Nintedanib in progressive fibrosing interstitial lung diseases[END_REF]. Briefly, patients had a physician-diagnosed chronic fibrosing ILD other than IPF, reticular abnormality with traction bronchiectasis (with or without honeycombing) of > 10% extent on HRCT, FVC ≥ 45% predicted, and diffusing capacity of the lung for carbon monoxide (DLco) ≥ 30% to < 80% predicted. Patients met one of the following criteria for ILD progression within the 24 months before screening, despite management deemed appropriate in clinical practice: relative decline in FVC ≥ 10% predicted; relative decline in FVC ≥ 5 to < 10% predicted and worsened respiratory symptoms; relative decline in FVC ≥ 5 to < 10% predicted and increased extent of fibrosis on HRCT; worsened respiratory symptoms and increased extent of fibrosis on HRCT. Patients taking azathioprine, cyclosporine, mycophenolate mofetil, tacrolimus, rituximab, cyclophosphamide, or oral glucocorticoids > 20 mg/day were not enrolled. Initiation of these medications was allowed after 6 months of the trial in cases of deterioration of ILD or autoimmune disease. Patients at risk of bleeding (defined as genetic predisposition to bleeding; requirement for fibrinolysis, full-dose therapeutic anticoagulation or high-dose antiplatelet therapy; hemorrhagic central nervous system event within 12 months; hemoptysis or hematuria, active gastrointestinal bleeding or gastrointestinal ulcers, or major injury or surgery, within 3 months; or international normalized ratio > 2, prolongation of prothrombin time and activated partial thromboplastin time by > 1.5 times the upper limit of the normal range (ULN) were not enrolled. Patients were excluded if they had a history of severe uncontrolled hypertension (≥ 160/100 mmHg) within 6 months, myocardial infarction within 6 months, unstable angina within 6 months, thrombotic event (including stroke and transient ischemic attack) within 12 months of screening, or significant pulmonary arterial hypertension.

Patients were randomized to receive nintedanib 150 mg twice daily (bid) or placebo, stratified by fibrotic pattern on HRCT (usual interstitial pneumonia [UIP]like fibrotic pattern or other fibrotic patterns). Patients received one capsule bid administered orally. The trial consisted of two parts (Additional file 1). Part A comprised 52 weeks of treatment. Part B was a variable period beyond week 52 during which patients continued to receive blinded randomized treatment until all the patients had completed the first 52 weeks of the trial and the benefit-risk of nintedanib over 52 weeks had been assessed. Patients who discontinued treatment were asked to attend all visits as planned, including an end-of-treatment visit and a follow-up visit 4 weeks later. Patients who were still on treatment at the end of Part B were eligible to enter an open-label extension study, INBUILD-ON (NCT03820726). The final database lock took place after all patients had completed the follow-up visit or entered INBUILD-ON. Data collected up to the final database lock (i.e. in Part A and Part B) are referred to as data collected over the whole trial.

Treatment interruptions (for ≤ 4 weeks for adverse events considered related to trial medication or ≤ 8 weeks for other adverse events) and dose reductions to 100 mg bid were recommended to manage adverse events. No time frame was specified for the duration of dose reduction. After resolution of the adverse event, nintedanib could be reintroduced and/or the dose increased back to 150 mg bid. Specific recommendations were provided to the investigators for the management of diarrhea and hepatic enzyme elevations (Fig. 1). Adverse events were reported irrespective of causality and coded according to preferred terms in the Medical Dictionary for Regulatory Activities (Med-DRA) version 22.0.

Analyses

Compliance with trial medication was calculated as the number of capsules taken × 100 divided by the number of capsules that should have been taken. Dose intensity was defined as the amount of drug administered divided by the amount of drug that would have been received if the 150 mg bid dose had been administered for the planned treatment period or until permanent treatment discontinuation.

We analyzed the proportions of patients with any adverse events, any serious adverse events, and any adverse events leading to treatment discontinuation over 52 weeks (or until 28 days after the last intake of trial drug in patients who discontinued trial drug before week 52) and between the first trial drug intake and 28 days after the last trial drug intake (i.e. over the whole trial). Serious adverse events were defined as events that resulted in death, were life-threatening, resulted in hospitalization or prolongation of hospitalization, resulted in persistent or clinically significant disability or incapacity, were a congenital anomaly or birth defect, or were deemed to be serious for any other reason. The intensity of an adverse event was categorized by the investigator as mild (awareness of signs or symptoms which are easily tolerated), moderate (enough discomfort to cause interference with usual activity), or severe (incapacitating or causing inability to work or to perform usual activities). Based on the mechanism of action of nintedanib [START_REF] Wollin | Mode of action of nintedanib in the treatment of idiopathic pulmonary fibrosis[END_REF] and its known adverse event profile in patients with IPF [START_REF] Richeldi | Efficacy and safety of nintedanib in idiopathic pulmonary fibrosis[END_REF], we present data on diarrhea, liver enzyme and bilirubin elevations, bleeding, and cardiovascular adverse events. Analyses were descriptive and based on patients who received ≥ 1 dose of trial drug.

Results

Patients

A total of 663 patients received ≥ 1 dose of trial drug (332 nintedanib, 331 placebo). The baseline characteristics of the trial population have been described [START_REF] Flaherty | Nintedanib in progressive fibrosing interstitial lung diseases[END_REF][START_REF] Cottin | Nintedanib and immunomodulatory therapies in progressive fibrosing interstitial lung diseases[END_REF]. Briefly, mean (SD) age was 65.8 (9.8) years, FVC was 69.0 (15.6) % predicted; 53.7% of patients were male, 62.1% had a UIP-like fibrotic pattern on HRCT. The most common diagnoses were hypersensitivity pneumonitis (26.1%), autoimmune disease-related ILDs (25.6%), idiopathic non-specific interstitial pneumonia (iNSIP) (18.9%), and unclassifiable idiopathic interstitial pneumonia (17.2%). About half the patients (53.2%) were taking low-dose glucocorticoids (≤ 20 mg/day prednisone or equivalent), 4.7% were taking biologic disease-modifying antirheumatic drugs (DMARDs) and 11.6% were taking non-biologic DMARDs [START_REF] Cottin | Nintedanib and immunomodulatory therapies in progressive fibrosing interstitial lung diseases[END_REF].

Compliance and exposure

Over the whole trial, 34.3% of patients in the nintedanib group and 30.2% of patients in the placebo group permanently discontinued trial medication (for any reason). Among those who permanently discontinued medication in the nintedanib and placebo groups, respectively, 17.5% and 2.0% discontinued within 31 days; 15.8% and 12.0% discontinued between day 32 and day 91; 14.9% and 15.0% discontinued between day 92 and day 182; and 51.8% and 71.0% discontinued after day 182. Mean compliance with trial medication was 96.7% in the nintedanib group and 97.5% in the placebo group. Mean dose intensity was 91.5% and 98.4% in these groups, respectively. Median exposure to trial drug (at either dose) was 17.4 months in both treatment groups.

Dose adjustments

Almost half (48.2%) of patients in the nintedanib group and 15.7% in the placebo group had ≥ 1 dose reduction and/or treatment interruption. The most common reason for dose reduction or treatment interruption was diarrhea (Tables 1 and2). Information on dose reductions and treatment interruptions is shown in Tables 1 and2. A total of 131 (39.5%) patients in the nintedanib group had ≥ 1 dose reduction, of whom 41 (31.3%) had ≥ 1 dose reescalation. Twenty (6%) patients in the placebo group had ≥ 1 dose reduction, of whom 8 (40%) had ≥ 1 dose reescalation. Dose reductions were more common among female patients (49.0% of the nintedanib group, 8.4% of the placebo group) than male patients (31.3% of the nintedanib group, 4.0% of the placebo group) (Additional file 2). A total of 128 (38.6%) patients in the nintedanib group and 41 (12.4%) patients in the placebo group had ≥ 1 treatment interruption.

Dose adjustments and treatment discontinuations over 52 weeks are shown in Additional file 3. In patients who completed 52 weeks of treatment, the rate of decline in FVC over 52 weeks was similar irrespective of the dose adjustments used to manage adverse events of nintedanib (Fig. 2).

Adverse events

Adverse events over 52 weeks are described in Additional file 4. Over the whole trial, similar proportions of patients in the nintedanib and placebo groups had any adverse event(s) (98.2% and 93.1%, respectively). The most common adverse event was diarrhea, which was reported in 72.3% of patients in the nintedanib group and 25.7% of patients in the placebo group. Diarrhea occurred at a rate of 136.4 events per 100 patient-years in the nintedanib group and 23.0 events per 100 patient-years in the placebo group (Table 3). Adverse events in subgroups by sex, age, race and weight at baseline are shown in Additional file 5.

Adverse events leading to treatment discontinuation occurred in a greater proportion of patients in the nintedanib group than in the placebo group (22.0% versus 14.5%) (Table 4). The rate of adverse events leading to treatment discontinuation was 17.0 events per 100 patient-years in the nintedanib group and 10.3 events per 100 patient-years in the placebo group. Diarrhea led to permanent treatment discontinuation in 6.3% of patients in the nintedanib group and 0.3% of patients who received placebo.

Serious adverse events were reported in 44.3% of patients in the nintedanib group and 49.5% of patients in the placebo group. The most common serious adverse events in the nintedanib and placebo groups, respectively, were pneumonia (7.2% and 4.8%) and progression of ILD (5.7% and 13.6%) (Additional file 6). The proportion of patients with fatal adverse events in the nintedanib group (6.3%) was lower than that in the placebo group (10.9%).

Gastrointestinal and metabolic adverse events

Diarrhea, nausea, vomiting, decreased appetite, weight decrease, and abdominal pain were more frequent in patients who received nintedanib than placebo (Table 3). Among nintedanib-treated patients who experienced ≥ 1 diarrhea adverse event, most (87.8%) experienced events that were at worst of mild or moderate intensity (Table 5). Among nintedanib-treated patients who experienced ≥ 1 diarrhea adverse event, 8.8% permanently discontinued treatment due to diarrhea.

Hepatic adverse events

The proportions of patients with hepatic adverse events and elevations in hepatic enzymes and bilirubin were greater in patients treated with nintedanib than placebo (Table 6). Elevations in alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) to ≥ 3 times the ULN were observed in 47 patients (14.2%) in the nintedanib group and 6 patients (1.8%) in the placebo group. Among the 47 nintedanib-treated patients with these elevations, the elevations were observed ≤ 30 days after the interruption. One patient in each treatment group had elevations in liver enzymes and bilirubin that met criteria for Hy's law; liver enzymes and bilirubin returned to normal ranges after discontinuation of nintedanib or placebo.

Bleeding adverse events

Bleeding adverse events were reported in 13.9% patients in the nintedanib group and 15.4% of patients in the placebo group (Additional file 7). The most frequent bleeding adverse event was non-serious epistaxis. One patient in each treatment group had a non-serious adverse event of gastrointestinal perforation. Serious bleeding adverse events occurred in 1.5% and 2.1% of patients in the nintedanib and placebo groups, respectively (Additional file 7). The most frequent serious bleeding adverse event in the nintedanib group was gastrointestinal hemorrhage (0.9% of patients).

Cardiovascular adverse events

In the nintedanib and placebo groups, respectively, hypertension was reported in 5.7% and 6.9% of patients, major adverse cardiovascular events in 6.3% and 5.1% of patients, and myocardial infarction in 1.8% and 1.5% of patients (Additional file 8).

Discussion

We used data from the INBUILD trial to characterize the safety and tolerability of nintedanib in patients with progressive fibrosing ILDs other than IPF. The adverse event profile of nintedanib in these patients was consistent with that observed in patients with IPF in the INPULSIS trials [START_REF] Richeldi | Efficacy and safety of nintedanib in idiopathic pulmonary fibrosis[END_REF][START_REF] Corte | Safety, tolerability and appropriate use of nintedanib in patients with idiopathic pulmonary fibrosis[END_REF] and in patients with SSc-ILD in the SENSCIS trial [START_REF] Distler | Nintedanib for systemic sclerosis-associated interstitial lung disease[END_REF][START_REF] Seibold | Safety and tolerability of nintedanib in patients with systemic sclerosis-associated interstitial lung disease: data from the SENSCIS trial[END_REF]. Consistent with the findings of the INPULSIS and SENSCIS trials [START_REF] Corte | Safety, tolerability and appropriate use of nintedanib in patients with idiopathic pulmonary fibrosis[END_REF][START_REF] Seibold | Safety and tolerability of nintedanib in patients with systemic sclerosis-associated interstitial lung disease: data from the SENSCIS trial[END_REF], diarrhea was the most common adverse event associated with nintedanib and was mild or moderate in most cases. Serious adverse events of diarrhea were rare. Fewer than 9% of nintedanibtreated patients who experienced diarrhea discontinued nintedanib due to this adverse event. The low rate of discontinuation of nintedanib due to diarrhea or other gastrointestinal adverse events suggests that the recommendations provided for management of these events were effective in minimizing their impact and enabling patients to remain on treatment, and that similar procedures should be implemented in clinical practice. The proportion of patients who permanently discontinued nintedanib over 52 weeks was similar in the INBUILD trial (24.1%) and INPULSIS trials (24.5%) and higher than in the SENSCIS trial (19.4%). The proportion of nintedanib-treated patients who had at least one dose reduction over 52 weeks was similar in the INBUILD trial (33.7%) and INPULSIS trials (27.9%) and lower than in the SENSCIS trial (40.6%). The reasons for this greater use of dose reduction are not known, but may be partly due to the greater proportion of female patients in the SENSCIS trial (75.2%) compared with the INBUILD trial (46.3%) or INPULSIS trials (20.7%), as dose reductions were more common in female than male patients. Among patients who completed 52 weeks of treatment, the rate of decline in FVC was similar irrespective of nintedanib dose adjustments. Despite this observation, we believe, based on a dose-finding study in patients with IPF, that a 150 mg bid dose of nintedanib is the optimal dose for slowing decline in FVC [START_REF] Richeldi | Efficacy of a tyrosine kinase inhibitor in idiopathic pulmonary fibrosis[END_REF]. Other than in patients with mild hepatic impairment, nintedanib should be initiated at this dose to ensure that patients receive the optimal benefit on slowing progression of ILD.

Previous analyses of data from the INBUILD trial have shown that the adverse event profile of nintedanib was consistent across subgroups based on ILD diagnosis [START_REF] Wells | Nintedanib in patients with progressive fibrosing interstitial lung diseases-subgroup analyses by interstitial lung disease diagnosis in the INBUILD trial: a randomised, double-blind, placebo-controlled, parallel-group trial[END_REF]. Here we showed that the adverse event profile of nintedanib was generally consistent across subgroups based on age, sex, race and weight, but nausea, vomiting and dose reductions were numerically more common among female than male patients. In the nintedanib group, ALT/AST increases were more frequent among patients who were female, Asian, or < 65 kg. The frequency of liver enzyme elevations in both the nintedanib and placebo groups was higher in the INBUILD trial than in the INPULSIS trials [START_REF] Richeldi | Efficacy and safety of nintedanib in idiopathic pulmonary fibrosis[END_REF][START_REF] Corte | Safety, tolerability and appropriate use of nintedanib in patients with idiopathic pulmonary fibrosis[END_REF] or SENSCIS trial [START_REF] Distler | Nintedanib for systemic sclerosis-associated interstitial lung disease[END_REF][START_REF] Seibold | Safety and tolerability of nintedanib in patients with systemic sclerosis-associated interstitial lung disease: data from the SENSCIS trial[END_REF]. No reasons for this could be identified based on the characteristics of the patient populations, including sex, race, weight and concomitant medication use, and it is likely largely explained by the use of a different central laboratory, which used different reference values, i.e., a lower threshold for the upper limit of normal, in the INBUILD trial than in previous trials. In most cases, elevated liver enzymes returned to within the normal range Table 5 Number, intensity and consequences for trial drug of diarrhea adverse events among patients who experienced ≥ 1 diarrhea adverse event in the INBUILD trial CTCAE: Common Terminology Criteria for Adverse Events [START_REF]Common Terminology Criteria for Adverse Events (CTCAE) (version 4.0[END_REF]. Adverse events reported between first trial drug intake and 28 days after last trial drug intake are shown. Median exposure to trial drug was 17.4 months in both groups. Data are n (% of patients who had ≥ 1 diarrhea adverse event and in whom additional information was collected) a Discontinuation of trial drug was considered the worst consequence, followed by dose reduction spontaneously or after dose reduction or treatment interruption. Liver function tests should be conducted prior to initiation of nintedanib, at regular intervals during the first 3 months of treatment, and periodically thereafter or as clinically indicated [START_REF]Ofev prescribing information[END_REF]. Immunomodulatory therapies are the mainstay of treatment for fibrosing ILDs other than IPF [START_REF] Wang | The Pulmonary Fibrosis Foundation Patient Registry. Rationale, design, and methods[END_REF][START_REF] Assayag | Treatment initiation in patients with interstitial lung disease in Canada[END_REF]. At baseline, glucocorticoids were taken by over half the patients in the INBUILD trial. To minimize the potential impact of immunomodulatory therapies on the assessment of the efficacy and safety of nintedanib, the use of certain immunomodulatory therapies was restricted. Use of nintedanib (other than as trial medication) and pirfenidone was prohibited. Previous analyses have shown that the adverse event profile of nintedanib over 52 weeks, including hepatic enzyme elevations, was similar between patients who did (n = 39) and did not (n = 293) use prohibited or restricted therapies at baseline or during treatment with trial drug [START_REF] Cottin | Nintedanib and immunomodulatory therapies in progressive fibrosing interstitial lung diseases[END_REF] and between patients who did (n = 187) and did not (n = 145) use DMARDs and/or glucocorticoids at baseline [START_REF] Chaudhuri | Does nintedanib have the same effect on FVC decline in patients with progressive fibrosing ILDs treated with DMARDs or glucocorticoids? Eposter presented at the European Respiratory Society international congress[END_REF]. A limitation of our data is that it was not possible to draw conclusions about the safety and tolerability of nintedanib used in combination with specific other medications, given the small numbers of patients using specific therapies and the differences between patients who were and were not taking those therapies.

As an inhibitor of the vascular endothelial growth factor receptor, nintedanib may increase the risk of bleeding [START_REF] Schmidinger | Understanding and managing toxicities of vascular endothelial growth factor (VEGF) inhibitors[END_REF]. In the INBUILD trial, bleeding adverse events and serious bleeding adverse events were not more frequent in patients treated with nintedanib than placebo, but it must be borne in mind that patients treated with fulldose anticoagulation, high-dose antiplatelet therapy or at high risk of bleeding were excluded. Pharmacovigilance data and other real-world evidence have shown that most bleeding events reported in patients with IPF treated with nintedanib were non-serious and that epistaxis and contusion were the most common bleeding events [START_REF] Lasky | Safety of nintedanib in patients with idiopathic pulmonary fibrosis: global pharmacovigilance data[END_REF][START_REF] Toellner | Early clinical experiences with nintedanib in three UK tertiary interstitial lung disease centres[END_REF]. It is recommended that patients treated with nintedanib who are on full-dose anticoagulation therapy be monitored closely for bleeding and anticoagulation treatment be adjusted as necessary [START_REF]Ofev prescribing information[END_REF].

Overall, the frequency of cardiovascular adverse events in the INBUILD trial was low. The proportions of patients with major adverse cardiovascular events or myocardial infarction were similar in the nintedanib and placebo groups. Data from clinical trials in patients with IPF have also shown that the incidence of cardiovascular events in patients treated with nintedanib is low and similar to that in patients who received placebo [START_REF] Noth | Cardiovascular safety of nintedanib in subgroups by cardiovascular risk at baseline in the TOMORROW and INPULSIS trials[END_REF]. It should be noted that patients with a recent history of myocardial infarction, unstable angina or stroke were excluded from clinical trials of nintedanib.

The open-label extensions of the INPULSIS and SEN-SCIS trials, INPULSIS-ON and SENSCIS-ON, suggest that the safety and tolerability of nintedanib in patients with IPF and systemic sclerosis are maintained with longterm use [START_REF] Crestani | Long-term safety and tolerability of nintedanib in patients with idiopathic pulmonary fibrosis: results from the open-label extension study, INPULSIS-ON[END_REF][START_REF] Highland | Continued treatment with nintedanib in patients with systemic sclerosis-associated interstitial lung disease (SSc-ILD): data from the SENSCIS-ON trial[END_REF]. Data from the open-label extension of the INBUILD trial, INBUILD-ON, as well as from registries and other real-world studies, will provide further information on the long-term safety and tolerability of nintedanib in patients with ILDs.

Conclusions

In conclusion, data from the INBUILD trial demonstrate that the adverse event profile of nintedanib in patients with progressive fibrosing ILDs other than IPF is consistent with its established safety and tolerability profile in patients with IPF and SSc-ILD. The adverse event profile of nintedanib is characterized mainly by gastrointestinal events, particularly diarrhea. Management of adverse events using symptomatic therapies and dose adjustment is important to minimize the impact of adverse events and help patients remain on therapy.

Fig. 1

 1 Fig. 1 Algorithm for the management of A diarrhea adverse events and B hepatic enzyme elevations in the INBUILD trial

  of treatment in 25 patients (53.2%), > 30 to ≤ 60 days after the start of treatment in 3 patients (6.4%), > 60 to ≤ 90 days after the start of treatment in 5 patients (10.6%) and > 90 days after the start of treatment in 14 patients (29.8%). For most of these cases (43 of 47 patients in the nintedanib group, 6 of 6 patients in the placebo group), liver enzymes returned to within the normal range spontaneously or after dose reduction or treatment

Fig. 2

 2 Fig. 2 Rate of decline in FVC (mL/year) over 52 weeks by nintedanib dose adjustment in the INBUILD trial

Table 1

 1 Dose reductions in the INBUILD trialData are n (%) of patients unless otherwise stated. Adverse events shown were reported between first trial drug intake and 28 days after last trial drug intake. Median exposure to trial drug was 17.4 months in both groups ALT alanine aminotransferase, AST aspartate aminotransferase a Adverse events were coded based on preferred terms in the Medical Dictionary for Regulatory Activities version 22.0. Adverse events that led to > 2 dose reductions in either treatment group are shown. Percentages are based on the total number of dose reductions

	Nintedanib (n = 332)	Placebo (n = 331)

Table 2

 2 Treatment interruptions in the INBUILD trial

	Nintedanib (n = 332)	Placebo (n = 331)

Data are n (%) of patients unless otherwise stated. Adverse events shown were reported between first trial drug intake and 28 days after last trial drug intake. Median exposure to trial drug was 17.4 months in both groups ALT alanine aminotransferase, AST aspartate aminotransferase a Adverse events were coded based on preferred terms in the Medical Dictionary for Regulatory Activities version 22.0. Adverse events that led to > 2 treatment interruptions in either treatment group are shown. Percentages are based on the total number of treatment interruptions

Table 3

 3 Most frequent adverse events (reported irrespective of causality) in the INBUILD trialData are based on adverse events reported between first trial drug intake and 28 days after last trial drug intake. Median exposure to trial drug was 17.4 months in both groups. Adverse events were coded based on single preferred terms in the Medical Dictionary for Regulatory Activities (MedDRA) version 22.0, except for abdominal pain, which was based on a group of MedDRA preferred terms. Adverse events with a rate > 10 events per 100 patient-years in either treatment group are shown ALT alanine aminotransferase, AST aspartate aminotransferase a Based on MedDRA preferred term "interstitial lung disease"

		Nintedanib (n = 332)	Placebo (n = 331)
		n (%)	Rate per 100	n (%)	Rate per 100
			patient-years		patient-years
	Diarrhea	240 (72.3) 136.4	85 (25.7) 23.0
	Nausea	100 (30.1) 30.8	33 (10.0) 7.6
	Vomiting	64 (19.3) 17.3	16 (4.8)	3.5
	Abdominal pain	62 (18.7) 16.7	19 (5.7)	4.2
	Nasopharyngitis	54 (16.3) 13.9	48 (14.5) 11.4
	Decreased	54 (16.3) 14.0	23 (6.9)	5.1
	appetite
	Dyspnea	52 (15.7) 12.9	57 (17.2) 13.3
	Bronchitis	48 (14.5) 12.1	64 (19.3) 15.4
	Weight	49 (14.8) 12.4	18 (5.4)	3.9
	decreased
	ALT increased	49 (14.8) 12.4	13 (3.9)	2.8
	AST increased	43 (13.0) 10.8	13 (3.9)	2.8
	Cough	40 (12.0)	9.8	51 (15.4) 12.1
	Progression of	28 (8.4)	6.5	56 (16.9) 12.7
	ILD a

Table 4

 4 Most frequent adverse events that led to permanent treatment discontinuation in the INBUILD trial

		Nintedanib (n = 332)		Placebo (n = 331)
		n (%)	Rate per 100 patient-years n (%)	Rate per 100
					patient-years
	Any adverse event(s) leading to permanent treat-	73 (22.0)	17.0	48 (14.5)	10.3
	ment discontinuation
	Diarrhea	21 (6.3)	4.8	1 (0.3)	0.2
	ALT increased	6 (1.8)	1.4	1 (0.3)	0.2
	Drug-induced liver injury	5 (1.5)	1.1	0	0
	Progression of ILD a	3 (0.9)	0.7	12 (3.6)	2.6

Data are based on adverse events reported between first trial drug intake and 28 days after last trial drug intake. Median exposure to trial drug was 17.4 months in both groups. Adverse events were coded based on preferred terms in the Medical Dictionary for Regulatory Activities (MedDRA) version 22.0. Adverse events that led to permanent treatment discontinuation with an incidence rate of > 1 event per 100 patient-years in either group are shown ALT alanine aminotransferase a Based on MedDRA preferred term "interstitial lung disease"

Table 6

 6 Hepatic adverse events and elevations in liver enzymes and bilirubin in the INBUILD trialData are n (%) of patients with elevations reported between first trial drug intake and 28 days after last trial drug intake. Median exposure to trial drug was 17.4 months in both groups. Liver enzyme and bilirubin elevations are based on central laboratory data ALT alanine aminotransferase, AST aspartate aminotransferase, ULN upper limit of normal a Based on the standardized MedDRA query 'liver related investigations, signs and symptoms' (broad definition) which included preferred terms such as "ALT increased", "AST increased" and "gamma-glutamyltransferase increased" b One patient in the nintedanib group had elevations in ALT and/or AST ≥ 3 × ULN and bilirubin ≥ 2 × ULN based on local laboratory data. One patient in each group met criteria for Hy's Law

		Nintedanib (n = 332)	Placebo (n = 331)
	Hepatic adverse event a	87 (26.2)	24 (7.3)
	Elevations in ALT and/or AST
	≥ 3 × ULN ≥ 5 × ULN ≥ 8 × ULN Elevations in ALT and/or	47 (14.2) 14 (4.2) 3 (0.9) 0 (0)	6 (1.8) 1 (0.3) 1 (0.3) 1 (0.3)
	AST ≥ 3 × ULN and biliru-bin ≥ 2 × ULN b Elevation in total bilirubin
	≥ 1.5 × ULN ≥ 2 × ULN Elevation in alkaline phosphatase	3 (0.9) 1 (0.3)	6 (1.8) 1 (0.3)
	≥ 1.5 × ULN ≥ 2 × ULN	17 (5.1) 8 (2.4)	6 (1.8) 3 (0.9)

Acknowledgements

We thank the patients who participated in the INBUILD trial. The INBUILD trial was funded by Boehringer Ingelheim International GmbH (BI). The authors meet criteria for authorship as recommended by the International Committee of Medical Journal Editors (ICMJE). The authors did not receive payment for development of this manuscript. Writing assistance was provided by Elizabeth Ng and Wendy Morris of FleishmanHillard, London, UK, which was contracted and funded by BI. BI was given the opportunity to review the manuscript for medical and scientific accuracy as well as intellectual property considerations.

// clini caltr ials. gov/ ct2/ show/ NCT02 999178

Abbreviations

ALT: Alanine aminotransferase; AST: Aspartate aminotransferase; bid: Twice daily; CTCAE: Common Terminology Criteria for Adverse Events; DLco: Diffusing capacity of the lungs for carbon monoxide; DMARDs: Disease-modifying antirheumatic drugs; FVC: Forced vital capacity; HRCT : High resolution computed tomography; ILD: Interstitial lung disease; iNSIP: Idiopathic non-specific interstitial pneumonia; IPF: Idiopathic pulmonary fibrosis; MedDRA: Medical Dictionary for Regulatory Activities; SSc-ILD: Systemic sclerosis-associated interstitial lung disease; UIP: Usual interstitial pneumonia; ULN: Upper limit of the normal range.

Supplementary Information

The online version contains supplementary material available at https:// doi. org/ 10. 1186/ s12931-022-01974-2. Additional file 2: Table S1. Dose reductions and treatment interruptions in the INBUILD trial in subgroups by sex. S2. Dose reductions, treatment interruptions and exposure over 52 weeks in the INBUILD trial.

Additional

Additional file 3: Table

Additional file 4: Table S3. Adverse events over 52 weeks of the INBUILD trial.

Additional file 5: Table S4. Most frequent adverse events in the INBUILD trial in subgroups by sex. Table S5. Most frequent adverse events in the INBUILD trial in subgroups by age at baseline. Table S6. Most frequent adverse events in the INBUILD trial in subgroups by race. Table S7. Most frequent adverse events in the INBUILD trial in subgroups by weight at baseline. S8. Most frequent serious adverse events in the INBUILD trial. S9. Bleeding adverse events in the INBUILD trial.

Additional file 6: Table

Additional file 7: Table

Additional file 8: Table S10. Cardiovascular events in the INBUILD trial.

Authors' contributions

All authors contributed to the writing and critical review of this manuscript. All authors read and approved the final manuscript.

Funding

The INBUILD trial was funded by Boehringer Ingelheim.

Availability of data and materials

To ensure independent interpretation of clinical study results, BI grants all external authors access to relevant material, including participant-level clinical study data, as needed to fulfil their role and obligations as authors under the ICMJE criteria. Clinical study documents and participant clinical study data are available on request after publication of the primary manuscript in a peer-reviewed journal, and if regulatory activities are complete and other criteria met as per the BI Policy on Transparency and Publication of Clinical Study Data (https:// www. mystu dywin dow. com/ msw/ datas haring). Bona fide, qualified scientific and medical researchers are eligible to request access to the clinical study data with corresponding documentation describing the structure and content of the datasets. Upon approval, and governed by a Legal Agreement, data are shared in a secured data-access system for a period of 1 year, which may be extended upon request. Prior to providing access, clinical study documents and data will be examined, and, if necessary, redacted and de-identified, to protect the personal data of study participants and personnel, and to respect the boundaries of informed consent. Researchers should use the https:// vivli. org/ link to request access to study data and visit https:// www. mystu dywin dow. com/ msw/ datas haring for further information.

Declarations Ethics approval and consent to participate

The INBUILD trial was conducted in accordance with the principles of the Declaration of Helsinki and the Harmonized Tripartite Guideline for Good Clinical Practice from the International Conference on Harmonization and was approved by local authorities. The clinical protocol was approved by an independent ethics committee or institutional review board at each participating center. All patients provided written informed consent before study entry.

Consent for publication

Not applicable.

Competing interests

VC reports grants from Boehringer Ingelheim (BI); consulting and/or speaker fees from AstraZeneca, Bayer, Merck Sharp & Dohme, BI, Bristol-Myers Squibb (BMS), FibroGen, Galapagos, Novartis, Roche/Promedior, Sanofi, Shionogi; travel fees from BI and Roche/Promedior; and participation in a Data Safety and Monitoring Board for Celgene, Galapagos, Galecto and Roche/Promedior. FJM reports grants or contracts from Afferent/Merck, Bayer, Biogen, Nitto, Respivant, Roche, Veracyte for participation in Steering Committees of ILD studies; consulting fees from AbbVie, BI, BMS, Bridge Biotherapeutics, CSL Behring, DevPro, Genentech, IQVIA, Sanofi, Shionogi, twoXAR, Veracyte; honoraria for an internal presentation from United Therapeutics; and has participated on Data Safety Monitoring Boards or Advisory Boards for Biogen and BI. RGJ reports grants paid to his institution from AstraZeneca, Biogen, Galecto, GlaxoSmithKline, Pliant, Redx; consulting fees from BMS, Daewoong Pharmaceuticals, Pliant, Redx, Resolution Therapeutics, Veracyte; honoraria for lectures from AstraZeneca, Chiesi, PatientMPower, Roche; has participated on Data Safety Monitoring Boards or Advisory Boards for BI, Galapagos, Vicore; and has held unpaid leadership or fiduciary roles for Action for Pulmonary Fibrosis and NuMedii. JAB, HK and MMM have nothing to report. IT is a contractor to BI. CC and DL are employees of BI. UC reports consulting fees from BI, Genentech, Pliant, Roche; lecture fees from AstraZeneca, BI, Novartis, Roche; support for attending meetings from BI, Roche; and has participated on Data Safety Monitoring Boards or Advisory Boards for BI, Galapagos, Roche.

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