When a medicine moves forward in development, the starting assumption is usually that its potential efficacy is still believed in. I have often talked with colleagues about how our role is to recognise the risks around a medicine and look for ways to address them. The work could feel heavy if it were only about wrestling with uncertainty and setbacks, but that is also what makes it so compelling.
What I find most rewarding is being part of conversations with drug development experts from many different fields. There is real respect in that collaboration, because none of us could move a project forward alone. Around the table, there are often as many perspectives as there are experts, and somehow a path forward begins to take shape—by listening carefully and building on one another’s ideas. And sometimes, just as importantly, the decision is made that there is no path forward at all.
When a project has been carried forward for years, it can be especially difficult to admit that the real opportunities are gone. I have seen many projects kept alive year after year because new possibilities always seemed to appear, even as the likelihood of success kept shrinking. In hindsight, it is easy to say the project should have been stopped much earlier. Even so, every one of those experiences has offered lessons for the next difficult decision.
Only a small fraction of investigational molecules ever make it into patient studies, and during preclinical research, decisions on whether to continue or stop should be made smoothly and without unnecessary delay. The challenge in preclinical projects is that, regardless of the results, the question of whether the medicine will work in humans still remains unanswered.
When a medicine moves from research into development, I tend to think that the first clinical studies in humans are still part of research rather than development. At that stage, the key questions are whether enough of the compound reaches the body to produce an effect and whether tolerability is acceptable. There must also be a practical way to step back—adjust the formulation, return to preclinical work, and only then continue in the clinic.
In drug development, professional judgment often comes down to recognizing early enough when a project has reached the end of the road. Once a medicine has entered clinical development, the most common reason for failure is lack of efficacy—which is why the first patient studies, Phase II, are such a critical point. Interpreting the results and weighing the remaining options requires a cool head. Sometimes the data still offer a good reason to continue, for example in another indication, which means launching new Phase II studies.
If a medicine has several possible paths forward, the most expensive option is often to test them one by one, because a single study can take years and consume valuable patent life. That is why it is so important to explore opportunities in parallel and save time where it matters most. When results from several indications become available at the same time, the full picture is easier to see—and fewer open questions about efficacy are left hanging.
Decisions to stop for safety reasons may seem more clear-cut, but even then the discussion usually turns to whether the dose could be lowered, the formulation changed, or the medicine redirected toward alternative and more severe indications. Often, those conversations also mean talking about smaller patient populations and reduced market potential.
Behind every difficult decision lies careful, thorough reflection. Planning drug development through scenarios and built-in iterations can make decision-making easier, because part of the thinking has already been done in advance. And in many cases, quite a lot can be prepared with a reasonable amount of work even before the results are on the table.
Fortunately, despite the difficult moments, some projects do continue—and eventually lead to a medicine that can make a meaningful difference for patients. It is drug development professionals' job to judge which challenges are insurmountable and which can still be solved.