Reflecting or ruminating: listening to the regrets of life science leaders

Helen Mary Meldrum (NAS, Bentley University, Waltham, Massachusetts, USA)

ISSN: 1093-4537

Article publication date: 30 March 2021

Issue publication date: 15 June 2021

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Abstract

Purpose

The overwhelming frequency of failure in trying to bring a safe and effective biotech, pharmaceutical or medical device product to market is truly astounding. This research synthesizes industry leaders' insights on lessons learned from reflecting on professional disappointments.

Design/methodology/approach

This research used a qualitative approach to learning from the Chief Executive Officers (CEOs), Chief Scientific Officers (CSOs) and Chief Medical Officers (CMOs) of the most successful life science firms in the USA. A total of 45 industry leaders were interviewed regarding their lingering regrets about their career misadventures.

Findings

Regrets were unavoidable because there were opportunity costs for every choice each leader made. Commentary about wisdom gained comprised themes regarding valuable time lost, strategies that could have been enacted, products that failed and essential personnel who were not managed optimally. Contrary to expectations, there was little mention of money that was squandered.

Originality/value

Not felt as a solely negative emotion, regrets were recognized by these leaders as a potentially positive influence on their future decisions. Not felt as a solely negative emotion, regret was recognized by these leaders as a potentially positive influence on their future decisions. This exploratory study suggests that learning from retrospective and anticipated regrets benefits life science leaders in gaining clarity of thought regarding their current business challenges. Because prior research on the value of psychological regrets has mostly relied on limited samples, this inquiry contributes a new vantage point by examining a unique population of senior business leaders, thus providing broader applicability to the organizational literature.

Citation

Meldrum, H.M. (2021), "Reflecting or ruminating: listening to the regrets of life science leaders", International Journal of Organization Theory & Behavior, Vol. 24 No. 2, pp. 77-92. https://doi.org/10.1108/IJOTB-06-2019-0069

Publisher

:

Emerald Publishing Limited

Introduction

The US bioscience industry has reached $2 trillion in annual economic impact, holding a leading position as an economic force and job generator (Biotechnology Innovation Organization, 2018). Life scientists make breakthrough discoveries, which augment options for commercialized medical treatments, tests and devices. Leading a commercial bioscience company is a colossal challenge, with frequent restructuring, mergers, acquisitions and liquidations. C-Suite executives of these organizations must balance the needs of scientific precision and investors' interests. Leaders manage the unpredictable journey of innovation while planning to gain the approval of regulatory agencies and, at the same time, retain their best employees without going over budget. In this precarious product development process, missteps are inevitable. Misjudgments can cost time and money and often lead to the demise of a promising project, or cause a company to be liquidated or be acquired for the remaining assets (Shepherd, 2018). In life science product development, failure is the norm. Over 90% of biotech and pharma companies that advance a product as far as clinical trials never bring that once promising product to market. The costs to develop a new medication are estimated to be between$1.5 and almost 3 billion (Mestre-Ferrandiz et al., 2012; DiMasi, 2018; Ledley, 2018). In addition to the staggering amount of money required, there is an enormous investment of time. From preclinical testing of a new drug to approval takes an average of 12 years and about 7 years for a new medical device (Van Norman, 2016). The leaders of life science organizations never experience a simple sprint to a victorious finish line. This research reveals some of the emotional residue that lingers from the years of preparation for and running of the marathon product development process. This inquiry asked elite leaders (defined as corporate professionals who have achieved a high status in their industry) to be honest about their psychological experience of felt regrets about the product development process. Professionals reflecting on similar project work have commented on how utterly consuming this process can be: “I put my entire heart, my blood, my entire skill, my entire motivation into the [failed] project,” and “[y]ou are better to ask how many hours I did not invest in my work—there were very few” (Shepherd et al., 2011, p. 1,231). Dedication in the face of grim odds is expected from life science professionals, and the present inquiry sought to better understand the impact of this type of psychological enmeshment. Leaders are often judged by how they respond to and recover from failures. To stay stuck with static regrets about past misadventures does not inform future leaning .This speaks to the quality of resilience. A synthesis of over 270 research articles provides a useful definition of resilience “as the process of negotiating, managing and adapting to significant sources of stress or trauma. Assets and resources within the individual, their life and environment facilitate this capacity for adaptation and ‘bouncing back’ in the face of adversity” (Windle et al., 2011, p. 2). It can certainly be said that resilience is required in a business with fewer top-selling drugs making it to the market and new regulatory pressures along with the aforementioned costs and risks associated with the product development process. Theoretical background With the ever-present probability of a major project failure, how life science leaders respond to setbacks is quite telling. Some reversals in research plans prove permanently fatal, while others can be partially salvaged by regrouping. Regret has been defined as a decision-related emotion that is felt when a selected outcome is, or is thought to be, less favorable than a nonchosen option (Connolly and Zeelenberg, 2002). When C-Suite officers make unfortunate choices, their teams, and perhaps the leaders themselves, may question if they let unfiltered emotions get in the way of clear judgment. A review of the literature on psychological regret revealed a focus on how individuals think back on episodes across their life span and sparse research on how regrets affect organizational dynamics (Roese and Epstude, 2017). Because people imagine that a project would have had a better result if they had made different decisions, this knowledge can create excessive self-blame linked to elements of counterfactual thinking (i.e. reasoning through alternative courses of action) and assumed personal agency for choices made (Zeelenberg and Pieters, 2007). Another theory of regret posits that actions taken produce greater regret in the short term, whereas actions omitted generate more remorse in the long run (Gilovich and Medvec, 1995). Although a disastrous choice cannot be reversed, restitutions or apologies can lessen the felt magnitude. However, there may never be an opportunity to fulfill the goals derailed by a lack of action. Anticipatory regret refers to beliefs about whether feelings of distress will follow from an action or inaction and these attitudes affect decision-making (Abraham and Sheeran, 2003). Foreseeing the possibility of painful regrets can help motivate people to make a better choice in the moment (DeWall et al., 2016). In contrast, dysfunctional strategies to prevent future regrets might involve avoiding feedback about outcomes or delaying decisions for too long. Resilience is defined as “the developable capacity to rebound or bounce back from adversity, conflict, and failure or even positive events, progress, and increased responsibility” (Luthans, 2002, p. 702). Coutu (2002) asserts that resilient business leaders have in common a deep acceptance of realities, a strong belief that life is meaningful and a talent for improvisation. Resilient people and companies face reality with staunchness, make meaning of hardship, and improvise solutions. Individuals who are resilient show more emotional stability and flexibility with changing demands. Resiliency may serve to restore some optimism after an experience such as a product program cancellation (Luthans et al., 2006). It may be that the capacity to reframe regrets is an essential part of resilient leadership in life sciences. Leaders who ruminate on regrettable choices may experience difficulties that interfere with productivity. Everyone makes mistakes, but some can be catastrophic (e.g. losing venture capital funding means widespread layoffs) making it harder to bounce back (Toussaint et al., 2017). Rather than defaulting to defensive, or avoidant responses, maintaining a reflective posture toward their workplace regrets may help leaders gain insight regarding their own culpability. Scholars in organizational behavior have noted that resilient leadership provides a means of counteracting weak or strategic misalignments as well as a way to respond to triggering events (Williams et al., 2017). The present inquiry offers an opportunity to listen to leaders reflecting on this process. Since the next crisis of project failure will always be looming, it is useful to learn to how life science leaders reflect on regret as it relates to ongoing adaptions. Thus, the impetus behind this exploratory study was the author's interest in the mindsets of leaders in life sciences. What is unique about studying these professionals is that in their world, failure is the norm. “For every drug that gains FDA approval, more than 1,000 were developed but failed” (Seyhan, 2019, p. 5). Although scholars have studied the emotional aftermath of entrepreneurial business failures (see Shepherd and Patzelt, 2017), the relationship between psychological regret and the learning curves of bioscience leaders has not attracted much attention. This inquiry is part of a larger study exploring the resilience displayed by elite leaders in the industry. Methodology This qualitative research interviewed Chief Executive Officers (CEOs), Chief Scientific Officers (CSOs) and Chief Medical Officers (CMOs) of some of the most successful life sciences firms in the USA. The overwhelming frequency of failure and the stunning amount of money spent trying to bring a product to market are daunting, so the questions put to participants centered on how they maintain adequate resilience to persevere. How do the leaders find, take and make meaning from the frequent failures? That was the larger inquiry this research set out to answer (a project currently entitled: Forward from Failures: Profiles of Psychological Perseverance in Life Science Leaders). The leaders of the prestigious BioCentury 100 (BC 100) ranked companies (as indexed in 2015) were invited to participate. The BC100 list of the top 100 US life science organizations is based on market capitalization (BioCentury, 2015). Ten additional companies identified as top performers in 2015 by Forbes Inc. rankings were added to the list. Thus, the target group consisted of the CEOs and CMOs or CSOs of the BC 100, plus the Forbes index, which meant that approximately 250 professionals were candidates for participation. It was difficult gaining the cooperation of these prominent C-Suite executives, several of whom public data indicated were compensated at more than10 million annually [1].

Recruiting candidates was time-intensive, but resulted in interviews with 45 participants. The first approach used publicly available corporate addresses to send a letter by postal mail explaining why it would be beneficial to participate and the safeguards provided for any information collected. Participants were offered the opportunity to review the transcript of their interview for accuracy, to make edits and to be reassured that there would be no attempt at writing a negative exposé. The postal mailing yielded four respondents. Recruitment efforts through the online LinkedIn platform garnered no responses. Persistent follow-up yielded the rest of the sample. A strategy of informed conjecture was used to find the direct email addresses of the executives (which were never published on the web). Often, an email address for an employee about six rungs down the organizational chart could be found in a newsletter or press release. Then, a strategy of filling in the leaders' names in the e-mail format was used to send an invitation. Personal referrals (knowing someone who knew the staff in the C-suite) resulted in gaining six participants. Networking through life science professional membership groups did not yield any respondents. Attending a public presentation by C-Suite executives in Massachusetts to issue a personal invitation yielded three participants.

Telephone interview projects with the general public in the USA routinely obtain response rates below 10% (Leeper, 2019). Kennedy and Hartig (2019) find that just 6% of Americans are willing to participate in a phone interview. Surveys of C-Suite management also suffer from depressed response rates for a variety of reasons. These professionals have excessive demands on their time. Leading a publicly traded company means that there is sensitive data that executives might worry about inadvertently revealing. Most surveys of top management capture very low levels of cooperation, and this has discouraged researchers from attempting to gain access to corporate elites (Bednar and Westphal, 2006). Thus, to have completed interviews with approximately 20% of the potential pool of eminent respondents was a favorable return.

There are few guidelines prescribing appropriate sample size in qualitative studies. Creswell (2007) recommends at least 20–30 interviews to facilitate pattern emergence, dimension growth and saturation of viewpoints. The flexible interview format allowed for the leaders to spend more or less time on any subtopic related to failure in life sciences, allowing the respondents to think carefully and fully about the issues. This process resulted in 25 out of the 45 participants speaking directly about regrets.

The research plan and subject protections were documented and approved by Bentley University's Institutional Review Board (IRB) [2]. The interviews were conducted by telephone, digitally recorded, downloaded into audio files and transcribed. The process of scheduling phone appointments with overbooked leaders was time-intensive and spread over many months in 2015–2016. The interviews ranged in length from 45 min to over 2 h. Each transcript was sent back to every participant for review and a sign-off on the Bentley University IRB consent document. Without control over final approval of their own transcripts, it is unlikely that any of these high-profile leaders would have granted an interview. Follow-up was needed to clarify some transcripts because participants used terms including chemical formulas or the names of nonexistent companies that had liquidated. IRB guidelines for safeguarding and storing data were followed.

After a literature review to inform possible areas of inquiry, a flexible interview guide was formulated. The goal was to conduct a conversation and remain open and adaptable to the interviewees' priorities. Since the interviewer can control the quality of the results, background training was crucial. This investigator has decades of experience in counseling psychology and teaching listening skills that enabled effective facilitation. Preparation included thinking about possible questions regarding career issues and resilience in the face of failure. And, as is the focus here, some participants recalled their most memorable regrets.

The manifest content of the verbatim transcripts was analyzed, followed by an interpretation of the latent content. Braun and Clarke's (2006) Thematic Analysis method was employed. In brief, the six steps of this method are: familiarization with the data, generating preliminary codes (coding is defined as identifying text excerpts that are linked by a common idea), using the codes to look for emerging themes, reviewing the themes, naming and defining the themes and subthemes and reporting the data with illustrative quotes for each theme. Thematic analysis elicits the meaning in the data without contaminating it with preconceived ideas. This method was germane given that so little is known about the phenomenon of regret in life science corporate settings.

Accordingly, the transcripts were read and then reread to assign initial codes. Data reduction collapsed passages into potential themes. Themes were reviewed to ascertain whether the meaning in the data could be better represented by a different configuration. Each theme was defined and supported by quotations. For example, one interviewee said, “I realized that the most precious commodity was not the dollars, it was time....” and another said “The original timeline that was given out was too short....” Thus, both were included in a grouping about regrets regarding precious lost time. The stages of thematic analysis seem sequential, but they were actually a recursive process that became a more accurate portrayal of the data with increasing iterations. There were many checks on the raw data to confirm that the resultant descriptions were veracious.

Interrater reliability was not calculated, but informal debriefing with colleagues working in life sciences assisted in seeing patterns in the data and furthering the development of internal validity. Final responsibility for the results rests with the author for an additional and unusual reason. As part of a covenantal relationship with the elite corporate leaders, a promise was made that their data would only be handled by her.

Computer-assisted analytic software is easy to use and freely available. A decision was made to stay close to the data and forgo use of NVivo or similar programs. Firsthand experience with NVivo in a large, mixed-methods study led the author to conclude that manual analysis can code with more nuance than software (Simon et al., 2018). Seeing connotative significance in the subtext of a narrative and recognizing layered meanings and in-group references cannot yet be programmed via computer. The semantic subtlety of language makes these types of tasks less valid even with widely implemented programs.

Results

Participants spoke candidly despite needing to maintain an awareness of their public persona. However, some respondents were not reflecting on events inside their current place of employment. They were invited to reflect on any moment across their career span. Because of the sensitivities involved in leading public companies, several used examples from prior positions.

Because critics of the industry often mention exorbitant prices, it was surprising that the interviewees seemed relatively unconcerned with the bottom line. Obviously, there was a need to make a profit, but there were no outsized regrets related to funding. This is a small sample of interviews and yet discernible themes emerged regarding regrets. Some focused on specific strategies that should have been enacted had they held a different business philosophy (11 comments). Another clustered around lamenting the passage of moments, the different ways that tempo affected their decision-making and productivity, questions about what could have been accomplished with that lost time, and as a result, thoughts about whether the outcome wound have differed (nine comments). Others were clearly still haunted by therapeutic agents that failed or were harmful (eight comments). A few expressed remorse regarding essential personnel who were not managed optimally (five comments). Some of the comments echoed the ubiquitous wistful feelings about “what could have been.”

What could have been accomplished with that lost time, and as a result, would the outcome have differed?

If there's anything that I regret, probably, it's having spent too long in the nuts and bolts of trying, like everybody else, believing in the value of incremental benefits and not raising my head earlier in my career to say “where's the bigger picture here?”

– CMO Moderna

This executive regretted moving too slowly and following the norm of incremental progress in research. Industry leaders want to save and change lives through huge forward leaps. Since the challenges are so immense, movement comes through small steps. Still, through the lens of hindsight, some leaders feel they could have done better.

Other regrets reflected the opposite sentiment, feeling rushed:

…we could do the project in a shorter timeframe I thought, okay, the time that's left is eventually still good enough, it's a lot of time, somehow we will make it. Unfortunately, we did not make it and this was the reason why the project almost failed. The original timeline that was given out was too short....That undermined my team's credibility… That's something I would not do again.

– Senior VP Qiagen

Time is money, but the ways that the two constraints interact can tell the storyline. One CSO commented on the reticence of his company to spend on better pacing of testing and regretted not stepping in to push for a longer-range approach:

…. we had some really exciting follow-on molecules (more potent and selective) that we discovered in our labs and were ready for clinical development, but the investors were so focused on the near-term exit scenario of a big win that they did not want to invest in these earlier-stage assets. They would not let us even spend $2 or$3 million-- all it would have taken to get these through clinical proof of concept. If we had done that, we would also have some phase 2 data coming out at the same time as our lead drug trial failed and that would have been a completely different scenario around fundraising and survivability of the company. That was my biggest regret- not forcing the issue of funding these earlier stage assets....it taught me to not to tolerate short-sighted thinking.

– CSO Cubist

These comments did not communicate any sense of regret for having been too reckless. This is consistent with the aforementioned research indicating that people have a tendency to regret things they did not do more than things they did (Gilovich et al., 2003). This quotation conveyed a wish that the leader had been more assertive in pushing the funders toward higher-risk timelines. Does cautious behavior here suggest past negative outcomes from engaging in capricious actions? In hindsight, this executive wished he had been bolder. Seeing events in retrospect as more predictable than they were at the time a decision was made is called hindsight bias: the irrational idea of having been able to foresee a scenario emerging with prophetic accuracy. Hindsight bias also allowed some leaders to participate in the human habit of criticizing the decisions of others for their lack of acumen (Roese and Vohs, 2012).

Time was treated by most of these executives as an asset to be spent wisely. Carelessness with its passage stood out as a common regret:

…three or four years in, I realized that the most precious commodity was not the dollars it was time.... The wisest way to use money it is not to spend frivolously, but to go fast....The way I would have spent more is I would have hired more experts faster.... I do that now. I did not know enough to do it initially, and my greatest regret is that maybe I could have pushed us forward even faster ....

– CEO Seattle Genetics

Time, in this instance, was less about the career trajectory of the interviewee and more about the organizational focus that he tried to create. C-Suite executives felt acutely responsible for moving their projects along timelines that can be opaque and whose endpoints will always be unpredictable:

… I said I do not really see, based on the data we have, that we really can say we're going to be different than their molecule. We ended up almost de-prioritizing the program. I remember the team thinking we should push forward, and there was a lot of pressure in terms of the amount of money we were spending … we probably lost a year. ..we reinvigorated the program and really pushed it through, and now it's actually on the market. We lost time. The one thing about my regret, we lost time. Now the drug's on the market and it's transformed the company. The launch has gone way beyond what anyone could have imagined, how well it's done. I think my regret is that I knew that it was a drug, but I let some of these other considerations sway me too much....We were one year or two behind and probably should have been a little bit bolder in pushing.

– CEO Syros Pharmaceuticals

Despite the stereotypical concerns of time loss really being predominantly profit-motivated – this did not seem to be a major element of these descriptions. Participants expressed a keen sense of endangering or bypassing patients who could have benefited from earlier market debuts of products. In these cases, loss of time can be tragic:

….we had finished the phase one study, which was very successful, published it in the New England Journal of Medicine, but we did not get approved. Even though we had met our endpoints. We were forced to do a phase three study, and in that process, because I knew it was going to take a couple years to get through all that… patients who were too sick to be in a phase three, and were not going be around long enough, (their) parents were begging us to treat them, but I couldn't … To do it promptly, we did not have a lot of extra supply but we had enough just to get by, and we did not treat anyone. ...and in the end I did not get those kids treated, and three of them died. You know, I promised myself that wasn't going happen again. Because I think about that all the time.... even if we couldn't save them, we did not give them a chance, right?

– CEO, Ultragenix

Here the sense of a faster path-not-taken went beyond one leader's choices and took on a larger and potentially more tragic cast:

I always wish we could go faster because I know that there are patients who have cancers that they're dying of right now. We may have a drug that would help them. I'd like to be able to get it to them as fast as possible.

– CMO Seattle Genetics

There were also regretful comments on the pace of career trajectories:

In hind-sight … I wish I understood how much I enjoy small company entrepreneurial ventures because I would have done this earlier in my career.

– CSO Epizime

Maybe if I'd made an earlier transition to industry … maybe I would have been better in phase with the market dynamics. … The people who made the same moves that I did but five years earlier, were riding successes and not dealing all the time with the troughs in the industry.... my family would say it would have been an easier life if I'd been around for some of the peaks…

– CMO Pacira Pharmaceuticals

… It's that I did not come into the industry maybe a year or two earlier. The reason I say that is because I've learned a lot.... It's been really a great platform in which you are not only involved in the science, (but also) the clinical care, regulations, the economics, the social aspects.

– CMO Sanofi

Some comments reflected retrospective wisdom, something that nobody could be expected to know without the essential experience.

One interviewee noted that he was a successful university researcher, but still wistfully thought he could have done even better with industrial experience under his belt:

I was a successful academic doc, but I wish I had the discipline then that working in industry imposed. It's kind of like going to boot camp....“Okay, what's our objective? What's deliverable? What's the end result? If it goes this way, what are we going to do? If it goes that way, what are we going to do? And how are we going to communicate the results? And how's that going to happen?” We do this on timelines.…

– CMO Cempra

A few interviewees expressed a sense that they may have missed out on a career pivot, which they wished they had known that they were better suited to, or, in some cases, that a different aspect of the industry would have given them more leverage.

Regrets also have the potential to inspire a new philosophy. There were reports of learning and integrating major lessons based on this balancing act, of weighing the fear of failing against potentially positive outcomes:

Never let the fear of failing stop you from doing something, that's something that I really hold in my core.

– CMO Receptos

The leaders acknowledged that pushing through that fear can be challenging, especially in the biosciences industry. A vivid alertness to opportunity was a skill that developed over time and informed decisions:

You have to know when to hold and when to fold, as they say. It's a sense that … I have saying, “Hey, we do not belong in this market, in this business, in this research program,” [versus] We're going to take this all the way because it's going to work and that's it.

– CEO Arena Pharma

A sharpened awareness of what the contrasting outcomes could have manifested gave executives a more flexible and accommodating mindset for those dualities. They could now look back on the chaos of a research pathway with useful lucidity:

I am now fully capable of holding two thoughts that are diametrically opposed in my head at the same time, and two emotional states I remember thinking very clearly, “All is lost,” and “Wow, this is an interesting problem to try to solve.”

– CEO Vertex

Regret has the potential to inspire novel strategies and be beneficial for bringing their organizations to a more realistic position when facing these intensely risk-laden scenarios.

Apparently worried about feeling regret in the future, an interviewee recalled bringing up the risks up about a project, even while colleagues were trying to keep the “bad news” out of the discussion:

My executives were freaked out, and saying “Why are you bringing everybody down?” Well, it's not about bringing everybody down, it's about making sure that they understand that we're not looking at this business through rose-colored glasses, but in fact we were doing a lot of scenario planning,…If something happens, I want these guys to say, “Okay, they said it might happen, but they've got a plan.” To me, that's part of the process of building resilience in organizations, so that people do not experience these kind of ridiculous lows through times of bad news.

– CEO of Receptos

The executives sometimes found themselves pushing back against not only their own instincts, but also the group's will as a whole:

The easiest answer is always no because it's the lowest risk answer in the short term but it can often be the biggest risk answer in the longer term,…. When you're in that moment and it is the short term and you are with a group of very talented people as a group you are more likely even than as an individual to get a no answer, because everyone kind of softens each other's edges in conversation and you wind up defaulting to the risks that you are seeing.

– CEO Acorda

Even though the process is daunting, leaders reported that experiencing both the successes and the failures engendered an emotional attachment that enhances dedication to their work:

I think I had trouble dissociating myself from that failure.... I think that there is a separation generally, like when you sell a company… At the time, everyone went, Wow, that was a big success. I think that separation with something you like … it's a bit of divorce, I see drugs like your children. They're not perfect, but you've gotten to know them, and you've got to help them, hopefully, to the best that they can be, you know?”

– CMO of Intercept

Regret helped many to redirect their strategic plans and reprioritize their goals:

… our ability to raise further funding was hit badly. It was more of a financial setback, because we continued to take the same drug forward… but in the end it was like any example of what does not kill you makes you stronger,

– CSO of Acorda Therapeutic

The organizational response to missteps could prompt reconstruction of a company's priorities:

We were able to retreat behind the walls of our core group and focus in more intensively on the things that we felt made the most sense in terms of taking things forward. That process, which was ten years ago now, left us primarily with the projects that we have still on board as well as a few things we brought in since then.

– CSO Acorda Therapeutic

With clinical safety always a critical consideration, leaders had to balance forward momentum with institutionally mandated caution. Regrets in this area were not so easily pinned on personal or project-based factors, but respondents experienced them that way nonetheless:

I had another drug ...and it clearly worked but they were too timid to take it through… They got a very mild safety signal which they order to stop by, but I do not think they're right about that … that's more frustrations with bureaucracy and group thinking committee-based decision making than disappointment with the project.

– CSO from Agenus

One leader mentioned that regrets taught him a hyperawareness of safety as a counterbalance to unrealistic hopes:

I'm always super vigilant about safety data and super vigilant about implementation, orchestration and quality of work so that we do not run afoul of the authorities from a compliance perspective. That we are reporting and watching patient safety. Sometimes being optimistic about the drug's potential and drug's success, I'm always very, very cautious, overly cautious.

CMO Relypsa

Recollected regrets reinforced the necessity for caution, as medications can perform differently when shifted away from their original indication. One spoke of the stunning effectiveness of drugs developed for one condition having no effect on another:

It's amazing. It's like what we saw also in some cancer drugs. Then it was expanded into psoriasis and rheumatoid arthritis. All of a sudden, it did not work that great anymore.

– CSO from Quidel

Anticipation of regret actually led to an industry-wide action:

We had a couple calls with the FDA and we agreed that, okay, we should stop treating patients with this… Over the weekend, what I did was something very unusual in any pharmaceutical executive's career. I called up my friends in other companies who had similar drugs and before all the legalities were ironed out, I said Look, we'll get the lawyers involved Monday morning, but here's what I need you to know.

– CMO from Moderna

Some of the strongest regrets felt by executives were in the interpersonal sphere:

I was just too naïve and too young to do [the project]. I managed, by persuasion, to convince others, [but]I feel bad that I was able to persuade people in a way, on an idea that today I would have been able to pick apart in a heartbeat, That's a regret, but I learned a lot.

– CEO Bluebird Bio

This interviewee talked about how the people on the failed project went on to get great jobs elsewhere. He took comfort in the knowledge that “nothing tragic” happened to them, but the possibility that something could have happened had weighed on him.

Another CEO stated that her biggest regret was about losing good people:

Has the culture failed to deliver in terms of what we all want, which is the culture of respect, recognition, where everybody is held to equal accountability? When I hadn't focused enough on those issues and I lost some key people… it always sets you back. It's just people are stars you want to have.

– CEO Halozyme

In some cases, the regret stemmed not from losing the right people, but errors in hiring the wrong people:

The most damaging impact on the decisions I made was picking the wrong people, the wrong person to do an important job. That's the piece that really hurts, because first it was a direct decision of mine as a business leader. Most of [those decisions] impacted a large organization where the teams suffered because of that choice of a leader.

– CEO Moderna

Creating the perfect team may be impossible, but that did not keep the leaders from feeling responsible for not getting the right combination:

I think probably the biggest regret that I would have is not building a deeper leadership team, says [I should have had] more people, more strength, on the leadership teams earlier.

– CEO from Exact Sciences

Whether the executives regretted undesirable outcomes with their colleagues, or with potential future patients, the personal caring they felt for people was obvious:

I still miss full time patient care. That's why I try and go to clinic a little bit… I think the trade- off is worth it because I think I've been able to fortunately make a bigger impact on a much larger group of patients than one by one, but I really miss full time patient care still now today. – CEO Agios

Money was mentioned indirectly when discussing regrets and it was seldom at the core of what these leaders grieved over. For example, a CEO mentioned licensing a preclinical program, which later was developed in quite a different way than the company had intended:

In retrospect it would have been great if we kept it, because we were not that far from the clinic and ....there's at least one company now with a multi- billion dollar market cap for a ....molecule that wasn't that dissimilar from ours, [but] we were about a year and a half ahead, It was a great learning experience that whenever you hand your best baby over to someone else they're not going to raise it the way you would necessarily.

He went on to say that efforts to keep the company in the black with lots of reserves were so that they could have future options:

I do not want to be dependent on a deal like that to get us the kind of money we need to move things ahead. I really would like to control our destiny ourselves.

– CEO Kyropharm

These leaders were aware of the need for funding, but balanced it against intangible considerations.

A CEO recalled passing on an acquisition because of cold feet around the target company's management:

We were worried that we were not getting a straight answer. We lost trust. We ended up passing on the company… That company today is … Obviously because of confidentiality I cannot get into specifics, but it's probably a $100 billion company right now. – CEO Analym Another echoed a regret for lost opportunities due to a decision not acquire a product: So you do not buy it. Somebody else does. And then you discover that it was the best thing in the world, (said with a laugh). I have had that a few times. – CEO Incyte Learning from these experiences can incite or inhibit future decisions, but overall, regrets were seen as meaningful in that they informed ongoing choices. Discussion The objective of this inquiry was to explore the memorable regrets of life science leaders as a template for examining their reactions to challenging events and outright failures. There was no evidence that the leaders experienced a diminished capacity to learn from the events they described. Instead, their retrospective learning was solidified without lingering interference from strong emotions. Still, some still lamented the unrelenting passage of time and how it can be unforgiving as crucial moments are lost on project work or years spent in a less than an ideal job for their skill set. Others mentioned strategic business planning errors that could have been avoided. Even knowing that failure is a reality of medical research, some leaders were still thinking about products that did not cure or actually caused harm to patients. A few reflected on their weak management skills having harmful effects on employees. Working in life sciences is unique in that all subsequent career undertakings are sure to bear some resemblance to previous failed ventures. It is possible that the repetitive similarity of the failing research process may make it easier to apply lessons from previous misadventures. Prior psychological research has established that regrets can be dysfunctional at times and have been linked with anxiety and depression (Roese et al., 2009). However, none of the leaders interviewed for this project indicated that they retained high levels of debilitating distress over past business woes, and this could be related to the fact that they all work in organizational cultures where project termination is considered commonplace. Also, finding benefits (i.e. “silver linings”) in the regret-eliciting events can counteract the negative psychological effects that would otherwise be emotionally depleting (Gao et al., 2014). These leaders' reflections indicated that regret can be a springboard to effective problem-solving rather than a downward pull toward paralyzing devastation. In life science businesses, it is imperative to show proof of concept as quickly as possible before consuming too much cash and human capital. Several leaders mourned valuable time that was lost. However, they did not endlessly recount frustrations, but rather saw the experiences as setting the stage for their present work. As mentioned, regrets about actions that are not taken can persist longer than those of actions taken (Gilovich and Medvec, 1995). This phenomenon was present: regrets about inaction in specific situations with the repetition of several quotations that began with “I wish I had…” sentiments. Consistent with established research, there were fewer regrets that were both severe and persistent and instead more wistful repentances that were mild but long-lived (Gilovich et al., 1998). Perhaps this also reflects the need to become accustomed to failure in order to survive in their chosen profession. Some commented on learning not to make the same errors again. Ruminations about other choices that could have been made can be painful, but they seemed to keep the thwarted goal scenarios in mind as a way to maximize the likelihood of future successes. This was exemplified by a CEO's comment about learning not to be too short-sighted. These executives were motivated to take action to remedy a regretted outcome. One mentioned persuading his team to follow his lead on an idea he later saw as inherently faulty. Feelings of regret accelerated their learning curves to inform more effective strategic choices. Because regret is a great educator, these leaders learned to trade off the pursuit of one goal for another. Feeling remorse from lost opportunities may facilitate the process of turning attention toward obtainable outcomes. Some researchers have speculated that intense regret creates “low psychological closure” that can actually enhance redirected energy toward achievable goals (Beike et al., 2009). This process was evident when a CEO paraphrased a variation of philosopher Nietzsche's maxim “what does not kill us makes us stronger” to capture his team's determination in the face of adversity. Lingering regrets can be seen as a window into deep-seated motives. Research has documented the mismanagement of relationships to be an influential regret. Emotionally intelligent managers have the ability to recover from negative emotions (Wong and Law, 2002). Interpersonal regrets may be especially intense because they can directly impinge on self-concept. This was evident in the statement by the CEO who felt he had hurt people in his company by making a hiring mistake, for example, “the wrong person to do an important job.” He expressed abiding regret about how the team suffered because of his error. The need for harmonious teamwork is a strong motive and when thwarted, can set the stage for long-term regrets. An essential part of any leader's job is to promote a healthy organizational culture. Good relationships can become the ultimate strategic advantage. One leader cross-examined herself, wondering aloud if she had done enough to shape an environment to retain her star employees. When outstanding researchers depart a life science organization, their former teammates are less likely to have the wherewithal required for major innovation. Effective leaders can put processes in place to facilitate the growth of the star's mentees. Using regrets to prompt proactive change can save some of the high costs associated with turnover of scientific and managerial talent (Tzabbar and Kehoe, 2014). Some of the leaders used the mechanism of anticipatory regret to keep a vigilant eye on safety data with human subjects. One aversive aspect of regret is that people who experience it think they should have known better. With a decision point at hand regarding canceling a project, avoiding too much risk is a way of avoiding regret. In the words of a CMO, opting for the “very cautious” choice leads to an outcome that can be known in advance to occur with certainty. Consistent with the extant research, the motivation to avoid regret may have prompted the leaders to intensify their efforts in order to circumvent the possibility of a negative outcome (Zeelenberg et al., 2000). This research on regret has the potential to contribute to future scholarship on recovering from business failures. The life sciences present an organizational context that prompts strong emotions. Researchers have given scant attention to the role of emotions in an industry that is routinely cruel to employees who have put in years of intense effort, very often laying off devoted scientists and managers who have given extreme dedication to the process. Rather than becoming ensnared in a cycle of rumination, the acquired resilience among leaders and teams in biopharma organizations may act as catalyst for repairing the inevitable ruptures. This qualitative inquiry focused on the psychological utility of regret and is a constructive addition to the existing scholarship on business project failures (Shepherd et al., 2011). The results can be synthesized alongside extant research exploring the emotional costs of failure. This contribution furthers understanding of the psychological sequelae of misadventures in medical product development and the resilience required to rebound. Conclusion Leaders who value normalizing the failure experience lessen the psychological blow (Shepherd et al., 2011). What is unique about studying life science leaders is that failure is the norm, with recent estimates of new product approvals still hovering below 10% (Thomas et al., 2016). Therefore, it is surprising that the possible influence of psychological regret on industry leaders has not attracted more attention from scholars in organizational theory. These experienced, elite leaders are subject matter experts with meaningful insights to share. This research has laid a groundwork for future inquiries on how missteps help leaders build resilience. Given the void of research and value of the information, the goal of this inquiry was to explore regret through a qualitative, interview-based investigation. The flexible interview approach and skill of the interviewer allowed the executives to talk openly about their experiences of regret, yielding a deeper understanding of the phenomenon than would otherwise have been possible using quantitative survey methodologies. Practical and theoretical implications Because a focus on regrets has been lacking in the organizational theory literature, explorations such as this inquiry demonstrating the upside of regrets may help to lessen the negative stigma. The information uncovered here has practical implications for improving the culture of learning within life science organizations. Sharing regrets can assist all bioscience professionals to better evaluate what works well and what does not. In a cash-limited, venture-capital-infused industry, it is important to move toward a direction quickly and there is much discussion of “faster failures.” Canceling troubled projects early when costs are lower greatly increases the odds of future success. Speaking candidly about lingering regrets could set an inspirational tone about showing up and moving onward expeditiously in the face of disappointments. There is an “anti-failure bias” that has been noted as impeding the process of deriving value from traumatic episodes in business (McGrath, 1999). Scholars have asserted that all professionals are socialized to distance themselves from failures (Cannon and Edmondson, 2005). This data on regretful failures is valuable because success never creates a crucial need to augment knowledge and, in fact, a series of triumphs can encourage myopic thinking. No leader interviewed for this research experienced an unbroken string of wins. They all spoke of their regrets and failures as having provided important guidance. Learning from the fault lines in life sciences is a largely untapped, potent source of information for organizational theorists to explicate. Wherever life science industry leaders migrate during their careers, they bring their regrets along with them. As much as senior leadership may feel the need to be stoic about the preordained disappointments associated with product research failures, their emotional reactions are real and inevitably influence their framing of future endeavors. This scholarship can inform the career pursuits of those aspiring to work in life sciences as well as experienced industry leaders who need to appreciate the value of learning from regrets. Limitations and future research Although the participation rate was good, the sample size was small and not random. The limited number of interviewees prevented meaningful comparisons across demographic groupings. Also, the data are now a few years old and several of the leaders have changed positions. A follow-on update would have been ideal. The design used does not allow for conventional measures of reliability and validity. There was an assumption of interpersonal trust in the data collection process that many forms of quantitative research do not require. It is impossible to explore, but the question naturally arises of whether there was a selection bias wherein the more resilient leaders were also more comfortable with volunteering to talk. While care must be taken not to generalize for these reasons, the results are intriguing and inspire further investigation. Additional research is needed on organizational behavior in the life science industry. Studies on a wide range of other trades have shown that negative emotions about failures can motivate a process of “sensemaking” (Ucbasaran et al., 2013). However, this study focused on the life science industry where failure is continuous. The present study can be used as a pivotal point of departure to better understand the emotion-informed decision-making of those involved in product development. Notes 1. I was able to access information about participant salaries and bonus data because publicly traded companies have that information freely available. Because their company names are given here, it feels insensitive to calculate their average income. At the time I interviewed these leaders, it appears that my respondents made a range of income from less than$1 million to slightly less than \$60 million per year. The periodicals that report on this aspect of life science businesses include salary.com, FiercePharma.com, The Boston Globe, The New York Times, The Wall Street Journal, The Associated Press and the America Federation of Labor and Congress of Industrial Organizations (AFL-CIO). (2018). Paywatch. Retrieved from https://aflcio.org/paywatch

2.

All participants signed a consent form allowing for the use of their full names. However, due to differences between the USA and the European Union privacy laws, an editorial advisement was given to simply identify each participant by company name and position in the organization. The author has a signed consent form on file for each participant. Since they are leaders of publicly traded companies, if further information is useful, their names can be accessed by looking up public records (e.g. who was the CEO of the named pharma or biotech company in 2016).

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Corresponding author

Helen Mary Meldrum can be contacted at: hmeldrum@bentley.edu