Why It Takes Forever to Get New Medicines to Patients: Clinical Trial Enrollment (part 1)

This is the first of a multi-part series on the challenges of finding the right patients for clinical trials. It’s written for an audience of non-experts in trial design and conduct, but who are interested in this important part of getting new medicines to patients (hopefully including an effective vaccine to the virus causing Covid-19). I’ll try to answer the questions: why does it take a long time to bring new medicines to patients and what part does enrolling patients into the study have in this challenge?

The series will touch (lightly) on topics including trial design, key steps in conducting the trial, and why enrollment can often be the longest part of doing a study.

My background includes over 3 decades in biotechnology and pharmaceuticals developing new therapies, so I have some familiarity with the challenges of conducting high-quality trials.

Introduction

Clinical trials are studies assessing the safety and efficacy of potential medicines for human diseases. They are the centerpiece of the complicated effort to develop new therapies. At least in theory, the medicine must prove itself in these studies to be allowed for human use. If the medicine works as expected, patients will be allowed to use it. If it fails – and most potential medicines don’t make it through clinical trials – then patients have been spared exposure to a useless or harmful drug.

The therapies put into clinical trials can be entirely new and untried against any disease or they may be an existing medicine repurposed to address a disease they weren’t originally intended for. Of great current importance, these trials can assess potential medicines against serious and mortal illnesses including cancer, heart disease, stroke, and diabetes as well as infections such as Covid-19. Trials may also determine the safety and efficacy of medical devices ranging from insulin pumps to ventilators.

The main audience for the trial results is usually not the public or even medical doctors, but rather regulatory agencies including the FDA (the US Food and Drug Administration), the EMA (European Medicines Agency, the EU counterpart to the FDA), SFDA China (the Chinese counterpart to the FDA), and other global authorities who review the results and either approve – or not – drugs to be given to patients. Trial results may also be published in scientific journals. The public is free to read these, but finding and accessing the journals may be tedious and the articles are written for experts rather than a lay person. Nonetheless, for a diligent member of the public, they can provide real insight into the qualities of a new medicine.

The next posting in this series will address who does these trials and how they’re set-up.

(Image above by Arek Socha from Pixabay)

Corralling Mavericks in Business (part 3) – or Mavericks as the Proverbial Canary in the Mine-shaft

This is part 3 and the final part of an on-going series about managing ‘difficult’, but valuable staff (i.e. ‘mavericks’) in a technology-intensive businesses.

Mentoring mavericks by working to instill some modicum of patience for the firm’s rules entails time and is a distraction for the maverick’s manager. The organization minimally needs to acknowledge this challenge and preferably provide training to their managers about assessing a maverick’s real worth for the organization and determining how much effort should be expended to keep them productive. Some line managers will be more inclined and capable of working with mavericks, so the organization can consider appropriately pairing these managers with the nonconformists.

Mavericks are iconoclasts so their survival depends on how important their talents are perceived to be and how forbearing the business is about a maverick’s idiosyncrasies. Even if this eccentricity is tolerated thanks to their line manager’s good offices, the organization as a whole may still signal ambivalence by providing few opportunities for promotion and/or increased remuneration. The first-line manager has an important role in mitigating this organizational doubt by helping the maverick to stay visible and by publicly crediting their contributions. Nonetheless, despite the manager’s cleverness, the organization’s immune system may ultimately reject the nonconformist so the manager needs to be prepared for this eventuality.

At the strategic level, there is inherent friction between a business’s impulse to encourage staff innovation while also seeking to control its pace and character. Some organizations attempt to resolve this friction by channeling improvements through senior management blessed activities and initiatives, but mavericks may threaten this arrangement by initiating ad hoc, bottoms-up efforts to originate new products, services and processes. As management doesn’t have a monopoly on novel ideas potentially benefiting the organization, so openness toward nonconformist thinking may benefit the business.

Of course, being a maverick isn’t a binary quality and many employees occasionally demonstrate nonconformist tendencies. However, challenges to the organization are usually limited as most staff members don’t have the raw talent to really shake things up and, moreover, they value predictability and stability even if they sometimes find the organization’s rules constraining.

Beyond whatever benefits an individual maverick provides to a given business, they also offer a window into the tension between employees and businesses particularly in tech-intensive sectors that depend on staff creativity to drive corporate R&D success; mavericks are a more extreme example of what ‘regular’ employees are capable of. Mavericks challenge the organization to define when an individual’s worth outweighs their descriptiveness and, when that balance tilts towards keeping the individual, how to manage their talent without undue organizational distortion. The first-line manager plays a critical – and often unsung – role in this effort. And, for all the regular staff who may offer up innovative ideas that are outside of corporate norms, how mavericks are treated is a gauge for how nonstandard, but potentially worthy, ideas are received by management. All staff members may feel freer to volunteer potentially really useful innovation where senior management is at least somewhat open to novel thinking. Further, this openness may allow the company to have a better chance of surviving in dynamic tech sectors.

Corralling Mavericks in Business (part 2) – or Mavericks Personify Thug-life in the Organization

This is part 2 of an on-going series about managing ‘difficult’, but valuable staff (i.e. ‘mavericks’) in a technology-intensive businesses.

Classically, mavericks ignore standard procedures when it suits them and are impatient with the diplomacy needed to garner support from corporate power centers. For these reasons, they’re often disliked. Paradoxically, they may also be admired for their originality and anti-authoritarianism, though these qualities are potentially disruptive to the business since an entire organization behaving without regard to corporate norms results in chaos.

To the extent that originality coincides with nonconformist attitudes, an ambitious business should seek to channel a maverick’s creativity while blunting their potential to distract the organization. Line managers are an important, but under-appreciated element in establishing this equipoise. The organization minimally needs to be aware of the challenges maverick’s present and provide training to their managers about assessing a maverick’s actual worth to the organization and determining how much effort should be expended to keep them productive – or keep them at all.

To exploit a maverick’s talents, their manager needs to fit a square peg into a round hole. The manager will have to explain the nonconformist to the organization and vice versa – though the maverick frankly may not care to understand the organization. Despite this, the manager should seek to teach business savvy to the maverick, what rules must be followed, where power resides and how to conform, at least nominally, to behavioral norms. Having a manager who is a good listener while also setting boundaries is important – it’s a bit like parenting. Particularly, the manager should coach the maverick about effectively developing their ideas within the confines of the business.

The manager also must mitigate the perception that the organization lets mavericks break rules that everyone else must follow. Concerns about favoritism will obviously erode team camaraderie. Certainly, there is justification for many business rules including keeping the feds off your back, the CEO out of jail and ensuring process consistency, predictability and scalability. Nonetheless, every organization has ineffective processes and mavericks may reveal processes that stymie progress for everyone, not just themselves. The line manager benefits the organization by escalating the nonconformist’s experience. This can improve a flawed aspect of performance across the organization.

Corralling Mavericks in Business (Part 1)

The tricky art of harnessing employee talent and encouraging a creative work environment while keeping an organization focused and maintaining discipline is one test of an effective manager. This is especially true in technology-intensive businesses, utterly dependent on novel, pattern-breaking innovation. What follows is the first of a series of three postings that touch on this important topic.

Introduction

How individual talent is mobilized for the enterprise’s collective good is critical to business success. However, employees vary in their allegiance to business goals and processes. While most company staff members are at least nominally respectful of business process and habit, organizations also have mavericks unconcerned with allegiance to corporate culture.

Central to this discussion is that mavericks must add significant value to the company; though they may flout rules, their activities must ultimately lead to significant improvements in the firm’s products or processes. Otherwise, they are simply difficult employees who may be terminated. Thus, the organization needs to weigh the worth that a maverick adds (e.g. patents filed, research breakthroughs, new products developed ahead of schedule and under budget) with the disruption that they cause.

While not all mavericks are inherently creative and productive, innovation may well require breaking with past practice and ignoring paradigms, so some exceptional staff may well demonstrate maverick behavior. Balancing the challenges of tolerating – perhaps sometimes encouraging – nonconformity with the benefits of innovation resulting from that nonconformity is a topic that subsequent postings will tackle.