Feature Patient Safety

# Can Big Pharma put patients first?

BMJ 2013; 346 (Published 21 May 2013) Cite this as: BMJ 2013;346:f3285
1. Edward Davies, US news and features editor, BMJ

Edward Davies speaks to the chief medical officers charged with keeping patient safety at the heart of the drug industry

When GlaxoSmithKline (GSK) paid out a $3bn (£1.9bn; €2.3bn) settlement last year it was the largest ever payout for a drug company and was headline news across the world.1 Within GSK, however, it had been seen to be coming for some time. When Andrew Witty took over as chief executive, problems were already on the horizon, says Ellen Strahlman, the company’s former chief medical office (CMO): “Andrew came in in 2008 and had this looming settlement in front of him and asked why did this happen? There were vocal concerns about the timeliness of some data and some major product liability issues, such as with Avandia.” Seeing something had to change one of Witty’s initial moves was to appoint Strahlman as the first of a new breed of chief medical officer for GSK, and for the industry as a whole. “This was the best way to stop conflict of interests and was a huge step forward for these companies, which is why I took the job,” says Strahlman. Since then there has been a movement within the industry to have a post such as this at or near the top level of almost every company. Given their relative novelty there are few examples of how far the individuals can influence a company in the long lifecycle of a drug, for example, and as yet it is hard to pin down their exact remit as nomenclature and responsibilities vary enormously between different firms. But common to all is the view that there needs to be a senior medical voice at the top table who speaks for the patient in terms of safety, who can be turned to by business leaders for a medical opinion and, importantly, puts the ethics of the business front and center. In the case of Strahlman, she says: “The CMO is the final decision making authority in GSK on matters of patient safety, accountable to the chairman of the audit committee of the board of directors, and in such matters cannot be over-ruled by either the chairman of R&D [research and development] or the CEO [chief executive officer]. The veto I had worked at GSK because I never had to use it, but in a perfect world would you need the role? No.” The cynical reader might see these roles as the presentable face of an industry with an image crisis. A few months ago a survey from PatientView—a UK based research, publishing, and consultancy group—found only 34% of patient groups surveyed thought that the industry had a positive image—an 8% decline on a similar survey the previous year.2 And Strahlman makes no play of hiding that such a face became necessary as well as desirable: “It is practical as well. I’d love to say it was pure from a holy mountain but the reasons were mixed.” But Annalisa Jenkins who oversees the role for EMD Serono, a subsidiary of Merck KGaA, in Darmstadt, Germany, stresses that regardless of motive it has been an important and positive step: “There has been a trend to this sort of CMO post over the past decade to focus on the patient in the early phases of research and development, and tailoring programs to meet their needs from the beginning. “In the past there was a bit of an attitude of, ‘how can we help commercial sell more medicine?’ Around the turn of the century that evolved. Industry had been through a difficult period of trust with society and government and we needed turn round a ridiculous situation where our reputation was not much higher than the tobacco industry. “This role has developed in the last 10 years and the industry was forced into it in some ways. “Good business and good science is not always the same thing but there was a realisation that it was very important to have an independent view on what is good evidence to ensure regulatory compliance, and then in that context how do we make a great business?” ## Advisory v operational The absolute independence of the CMO’s view varies from company to company. Although all CMOs would say that they are able to talk freely and regularly to all their business leaders right up to the chief executive, the degree to which their day to day work is within that business, adding a tension to their post, is variable. For example, the role of Michael Rosenblatt at Merck & Co and Tim Garnett at Eli Lilly and Company give them different positions within the company. “The role of the CMO at Merck is to serve as the voice of the patient and medicine within the company at its highest levels,” says Rosenblatt. “The function reports directly to the company’s CEO, Ken Frazier, and is part of the company’s executive committee. What may be unusual about the CMO role at Merck is that it’s separate from our R&D, commercial, and other functions, and is accountable to the board of directors. Some of the responsibilities that are part of the job description of other CMOs, such as pharmacovigilance, regulatory affairs, drug development, etc, have been intentionally omitted in the configuration of the position at Merck.” At Lilly, Garnett’s role is fully integrated into the operations of the company: “I report into the head of R&D where others may report to the CEO,” he says. “Each role is very different and mine includes leading safety, regulatory, and the health outcomes teams.” With 1500 reports, including such groups as the bioethics committee it is fair to say that the role is deeply entrenched into Lilly’s business. For pharma industry watchers, the independence of these roles is the key to their importance. Sidney Wolfe, director of the Health Research Group at Public Citizen, a consumer advocacy group based in Washington DC, told the BMJ that unless these roles have total independence they can be considered little more than “a purely PR [press relations] effort.” “Unless they are free to go public over decisions within the company they have little more than a cosmetic benefit,” he said. “Anybody can become a whistleblower and lose their job, but what would really make a difference would be if there is nothing at all to stop you going after your own company.” His view is echoed by Ed Silverman, the founding editor of Pharmalot, an influential website covering events in the drug industry: “It’s hard to know—especially from the outside—what kind of a difference, if any, such a person can make. The mission needs to be spelt out very clearly and the CMO must have something of a public face to underscore involvement in tough situations. “Being an ombudsman is never easy, but a good one requires a degree of authority and the freedom to speak up. That’s going to be tough for an industry that is much more concerned with regulation and litigation.” Jenkins, however, takes a different view on the post, believing that a CMO too distant from the day to day running is not always the best answer—a CMO embedded in the business can work better if internal conflicting interests can be managed appropriately. Jenkins herself is a former CMO and the EMD Serono CMO is one of her 2000 reports. She believes that being fully integrated into the business simply makes the role easier to discharge and its influence more deeply felt by the business. “Companies have chosen to reform these roles based on size, geographical footprint, and the risks they are willing to live with. You need a manageable organization. You see the same thing at insurance companies where some similar posts are operational and some purely governance. “But to be honest companies structure themselves by what risks they can afford to take. In companies that need to rebuild public trust you need a more signature CMO role to ensure the role of policy and public safety.” ## A question of influence If this article is the first you have heard of these posts you are far from unusual, and although they are having an increasing impact within their own companies, their lack of profile begs the question of how far they can influence their firm and the wider industry. One way they have sought to do this is by the creation of a roundtable of CMOs that meets three or four times a year. Some topics cannot be discussed, such as individual product development, and to a similar degree some of the CMOs can be quite cagey about details when being interviewed for this article, but “I have been particularly active in identifying areas that we can work on together,” says Rosenblatt. “I often leave these sessions with new thinking, new ideas, and practical thoughts and actions generated by discussions with my colleagues.” ## The challenges of the job The exact challenges discussed at these meetings and worked on within the roles vary again from post to post [see case study], but some themes do emerge. Issues of competing interest, benefit-risk, and access to health often crop up in conversations between the CMOs. The issue of transparency around research trial data has also been much in the press recently and, indeed, the subject of the BMJ Open Data Campaign, and that has translated into the CMO’s day jobs. “In 2004, Lilly introduced LillyTrials.com to provide ongoing information about Lilly-sponsored clinical studies,” says Garnett. “As the information needs evolve over time, Lilly continually looks at its policy and makes modifications as warranted. “We’re currently working on our position on making even more clinical trial data available under certain circumstances that ensure patient confidentiality and protect intellectual property.” The roundtable not only gives them a forum to discuss these issues but also a platform to tackle things collectively. Joanna Waldstreicher, a roundtable member and CMO at Johnson & Johnson explains: “There was an article in a paediatrics journal a while ago which was fairly critical of industry in terms of paediatric studies done across the world and questioning the ethics and review approval and how many patients in the study were from the US versus ex-US. “What we discussed at the CMO forum was that rather than one of the companies or one of the CMOs putting forward a response, we all take those things very seriously. Maybe we could work together and put forward responses to articles like that so that we can give our own account of the situations at our companies.” ## Responding to industry criticism The above example gives some contrast with a past where criticism might have been ignored, and now engaging with it makes up a key portion of the job for most CMOs. Waldstreicher thinks that there is not a broad understanding of how the science, research, and development works inside a pharmaceutical organization, which leads to some criticism but that the criticism itself can be quite healthy. “There is so much [industry criticism] out there,” she says. “I think a healthy R&D ecosystem challenges itself all the time in terms of how it could do better. And I think part of my particular role here is how can we continuously do better? How can we learn? So I think it’s all part of a healthy scientific ecosystem to be honest.” Jenkins echoes that feeling but does find some of the criticism difficult. “Some current debates call into question my personal integrity and the terms are too polarising and populist,” she says. “We do need to be allowed to operate as a commercial industry and find a pragmatic way to share data, for example. “I do not feel proud about what has occurred in the industry before, but how long do we have to pay for that? “There is always an inherent conflict between health and return to shareholders but I think a more ethical pharma sector is here to stay. There is now intent to put patients in the centre, which was not always the case. There was perhaps a laziness of leadership in the 90s—the statin years—when people could roll out of bed and make money, but the pipeline is drying up and the industry has moved on.” ## A brighter future? Wolfe, however, is not convinced that the industry has moved on, or, more importantly, can move on. “Positions like this have been tried before under different names, but usually when they get in and see they can’t change it how they want, they leave. “I don’t see that the necessary change can come from within the pharma industry. They have to be accountable to shareholders and every year for 40 years the profit margin has been between 15% and 20%. There’s no reason to think they will stop doing things the same way. “It’s up to the FDA to do more than they are doing and also the legislative branch of government. Until the penalties get much larger and until people are put in jail, it will continue.” But the CMOs argue they are being given more clout than in the past and the posts will evolve to meet new needs. Rosenblatt says there are “few templates” for the work the CMOs are doing now, which will allow them to look at new partnerships and initiatives Several CMOs foresee a future where their advisory role is increased and they are drawn out of the more day to day operations of the business. “We’ll see a trend that it doesn’t carry operational responsibilities so it has a little more independence,” predicts Garnett. “There is an inherent conflict in some situations [in doing such a role]. I see it becoming more externally focused—I’m more internally focused now but that may evolve.” “I see some change in the next five years,” concludes Jenkins. “Large companies will diversify their risk profile. The industry will need different people and skill sets. We’ll have more public health people and a different mindset— more patient-centric. “In short we’re looking at the medicalization of pharma.” But Silverman feels that at present there are too many questions still to be answered: “Advocating for patients is fine, but what mechanisms can and will they put in place to ensure that clinical trial data is disclosed? How will they know what’s going on inside their own companies? How can they successfully navigate calls to release patient level data when their employers insist this would jeopardize proprietary rights? To what extent will they work with the board and regulatory affairs to ensure that marketing—whether this involves advertising or distribution or journal articles—does not go overboard in ways that can place patients at a disadvantage? If R&D resources are scarce, will they have a say in which compounds and, later, which trials to pursue or will decision making continue to rely on marketing considerations?” At this early stage there’s no way of knowing whether the predictions of Jenkins’ or Silverman’s questions will dominate the future. What is more certain is that although the industry might be able to take the financial strain of another$3bn settlement, its reputation is largely in the hands of these roles to prevent them in future, and patients now at least have a public face to call to account.

#### What’s in the CMO’s in tray

Last December the FDA approved the first new drug in almost 50 years for the treatment of multidrug resistant tuberculosis, called bedaquiline (Sirturo). Although an advisory committee unanimously recommended accelerated approval for the drug, it has been controversial with groups such as Public Citizen, which immediately called for its removal. The results of research on it looked strong in converting a patient’s sputum culture from positive to negative compared with placebo, but there were also a considerable number of deaths in those given the drug (10 out of 79 v 2 out of 81 in the control group), and the approval on the basis of an early stage trial has been heavily criticized for a reliance on surrogate markers.3

Conversely, there is a huge need for new drugs in this area, and with little in the pipeline Médecins Sans Frontières have called the drug a “historic opportunity to tackle drug resistant TB.”

Joanne Waldstricher is the Johnson & Johnson CMO working on the product:

“The compound has only been through Phase 2, so we have limited data on it. And there were adverse events that came up as you would expect with any medicine. But usually when our medicines are brought forward for approval to the health authorities we have large Phase 3 trials where we have a larger data package for safety and efficacy. In this circumstance we had much smaller databases for the drug, but the efficacy was so startling, so impressive.

“From a public health perspective the fact that we could clear the sputum earlier and that the cure rate was so much higher, the experts who we brought in as well as the health authorities advised us that we should move forward quicker and work towards accelerated review and approval because the efficacy was so impressive. And so we put forward the data at the FDA advisory committee completely transparently.

“We spent a lot of time preparing to be sure that everything was out there. The efficacy was great, but there were some adverse events. It was really then up to the experts and the health authorities, and . . . they weighed in on it very strongly at the end of last year and approved the drug. We’re going to be sure that we work together with health authorities and other experts in TB around the world to be sure that the right patients have access to the medicine and that it’s used in the right way.

“It’s a good example of where I think the future is going, where there is more public-private partnerships that are important. In the United States it’s a particular case where we probably would not be the best to be distributing this product. It’s in the interest of public health that we work together with the governments, and other authorities like the WHO [World Health Organization], and the experts to distribute the drug.

“We’re also in a partnership for the development of this compound with the TB Alliance. They’re developing it for drug sensitive tuberculosis and we’re developing it for multidrug resistant tuberculosis. I see that as the future—more of a learning society working together, and public-private partnerships in the benefit of public health.”

## Notes

Cite this as: BMJ 2013;346:f3285

## Footnotes

• Competing interests: I have read and understood the BMJ Group policy on declaration of interests and have no relevant interests to declare.

• Provenance and peer review: Not commissioned; not externally peer reviewed.

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