"I've Got Bad News"...
Chief Medical Officers need to think about their tone when explaining why a development drug may go no further.
Good news is never difficult to impart. But no-one likes to hear bad news – and this is particularly true when that bad news spells the end of a pharma company’s hopes of a steady revenue stream and improved patient outcomes through the approval of a new product.
Clinical trial results might have been less impressive than expected in a certain sub-population, for instance, or perhaps a mode of action has simply not worked as well as anticipated. Maybe there are safety issues or previously unforeseen cost implications. Either way, the unhappy task of relaying these grim tidings falls, more often than not, to the Chief Medical Officer (CMO) of a company, who spends much of his or her time injecting regulatory reality into internal debates and speaking to senior executives, investors and the media when things go awry.
Voice of reason
Small wonder that the CMO – through being the voice of reason - can often find themselves the most unpopular person in the room. Dr Mark Weinberg, CMO and Managing Director at the Halloran Consulting Group, knows what this is like. He has been at the sharp – perhaps uncomfortably sharp – end of conversations with regulatory agencies in the US and elsewhere on numerous New Drug Applications and Biologic License Applications. In a 15-year career at top 20 pharma companies and micro-cap biotechs, he has worked across the development cycle in various indications, run a medical affairs organization and led a large global clinical operations group.
He has brought this knowledge to bear on a couple of recent case studies to see if CMOs can learn anything from them about the pitfalls of – and top tips for - delivering bad news. In April, Sarepta Therapeutics suffered disappointment after a FDA advisory committee voted against recommending the company's Duchenne muscular dystrophy drug, Eteplirsen. There is a serious unmet need for a treatment; the FDA has said it is keen on finding one and Sarepta had been publicly confident of a successful filing. But the FDA, as things turned out, was not convinced – not least over whether the study of just 12 patients provided sufficient evidence of the drug’s efficacy.
You can get caught up in the hopes and dreams and aspirations of the company. You need to let the data drive your conclusions, not try to fit your conclusions to the data.
In a separate case, the US Securities and Exchange Commission has alleged that Massachusetts-based biotech AVEO Pharmaceuticals misled investors by hiding the FDA’s concerns over its kidney cancer drug Tivozanib. In particular, the SEC suggests that the company did not reveal some information regarding the FDA’s recommendation that a second clinical trial was required.
Being a skeptic
“Those two cases are at one end of the spectrum,” Weinberg suggests. “With AVEO you wonder how all that played out and why things did not seem to be more up front. With Sarepta, perhaps folks are caught up in the effect on a few patients, without that ability to step away. The biggest thing that Sarepta illustrates is the need to step back from the data – to be a skeptic.”
In general terms, it is possible as CMO of any pharma organization to see your judgment clouded, he insists. “You can get caught up in the hopes and dreams and aspirations of the company. You need to let the data drive your conclusions, not try to fit your conclusions to the data.” If you have a small number of patients, for instance, or questionable figures, then it is probably best to be cautious – despite the commercial imperative to deliver ‘good news’. “We need to hold patient safety above all things,” Weinberg points out. “One of the key responsibilities of the CMO is challenging and interrogating the data.”
Prior to joining Halloran, he was SVP, Development at RestorGenex, a micro-cap pharmaceutical company where he managed pre-clinical development for two assets approaching Phase I. Surely pouring cold water on the results can be difficult when all your colleagues are desperate for their research to be leading in a positive direction? “It can be a difficult place to be in a small company,” he acknowledges. “When I was in a company with one product, you get so caught up in what you believe it can do. It takes a real effort to step aside and look at it.”
Weinberg has an impressive CV, with his past roles including VP, Global Clinical Science and Global Therapeutic Area Head, CNS and Pain, at Astellas. He was also VP, Medical Strategy and Medical Affairs at Lundbeck, and worked at Takeda and Abbott Laboratories.
There is a similar breadth in the therapy areas he has covered - they include oncology, ophthalmology, dermatology, hematology, rheumatology and women’s health – and his academic credentials are impressive: as well as his MD from Duke University Medical School, Weinberg has a BA in economics from Yale University as well as an MBA from Northwestern’s Kellogg School of Management.
It is interesting, then, that for all his experience and expertise, Weinberg believes that the key weapon in the CMO’s armory is the way he or she delivers the message. “You need to plot a path forward for the company, pointing out what the regulatory requirements might be, how the FDA or EMEA might be approached, what is the most aggressive stance we can take,” he says. “For instance, ‘if we ask for x we might get y’. You need to have as full a conversation as possible, versus saying ‘you can’t do that’ and not explaining why.”
CMOs who, in retrospect, seem to have delivered an overly hopeful view of the situation, may well not have been trying to mislead. “You might take an optimistic view of the data because it’s your baby, your product,” Weinberg points out. “You maybe have treated patients with it so have seen the benefits it can bring. It can be very difficult to put your biases aside, wherever you are. But you need to think of your responsibilities in the company in that case. It depends a lot on the situation you’re in: a lot of times the positive aspects of negative studies are discussed, but it’s about communication.”
So CMOs need to take all these disparate elements and explain them to the board and to the media. In practice they could best say something like this, Weinberg suggests: “We did this study, it was negative overall but there were some interesting results in this subset. The FDA expressed concern, we may need to do another study.’ You have to say the upfront stuff first. Broadly, it comes down to transparency and credibility: that’s not just a CMO thing, that’s corporate responsibility.”
How do we then recognize the information we have for what it is, rather than trying to fit the pieces to the predestined path that we’ve mapped out? So when you get the answer to question A, what is question B going to be? So much depends on the size and scope of the company - but it falls to the executive team to think about how you manage bad data.
While accentuating the positive is a reasonable approach, there is no room in the CMO’s modus operandi for actively coloring the data being presented. However, the CMO does need to balance the safety of patients with the business needs of the company. “The CMO needs to ensure the company is thinking about what the implications of this decision might be – just like the CFO [Chief Financial Officer] because the money might be going to run out!” he says.
Obviously, all cases are different – but do some common themes emerge? Is there a blueprint for managing expectations? “Think about scenario planning,” Weinberg suggests. “This is the idea that we’ve got a path, here’s what we want to happen and these are the next most likely scenarios. How do we then recognize the information we have for what it is, rather than trying to fit the pieces to the predestined path that we’ve mapped out? So when you get the answer to question A, what is question B going to be? So much depends on the size and scope of the company - but it falls to the executive team to think about how you manage bad data.”
In short, CMOs often have some choppy waters to navigate – but the way they impart bad news has a significant impact on the way that the life sciences industry operates. It can be complicated for the CMO to communicate effectively to different audiences which have changing needs and expectations. With that in mind, Weinberg believes there are fundamental similarities between what the CMO does and how a doctor interacts with someone they are treating – which means that CMOs already have the basic skills they need to communicate (perhaps unwelcome) news effectively.
“Think about how as a physician you learn to talk to a patient,” he concludes. “You need to have the understanding of the drug and what effect it has – and how to communicate that message. So you need to remember that, however far away you get from the doctor-patient relationship.”
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