The Road to a Lancet Paper

Fostering great teamwork is the key to success

Bernadet Santema is a PhD candidate at the department of cardiology at the university medical center Groningen under supervision of cardiologist Adriaan Voors. The general goal of their research is to reduce the burden of heart failure. One way to achieve that goal is by advancing personalized medicine. To that end, they studied sex differences and recently published their findings in The Lancet. Martijn Hoes interviewed them.

You recently published the results of an important study in The Lancet. Naturally, this was covered extensively. Bernadet, could you summarize your conclusions?

Bernadet: We studied the current recommended therapies for heart failure. Similar doses are recommended in male and female heart failure patients to date, despite evidence that these patients may very well differ biologically. This could mean that optimal doses of heart failure drugs are different for men and women. We studied this hypothesis in two large cohorts and found that women with heart failure already benefit from lower doses of these medications. The optimal doses for women appeared to be around 50% of the currently recommended doses, with no further decrease in risk at higher doses. In contrast, men had the best clinical outcome at dose levels that are in agreement with the current guidelines.

What drove you to do this research?

Bernadet: We wanted to study sex differences in relation to the effectiveness of current heart failure medications. Our research always starts with questions that are raised in the clinic, since these questions have the potential to really make a change in clinical practice. Fortunately, the required data was well documented in the large European cohort we used. It seemed like an obvious choice to conduct this research, it was just such a unique opportunity. The fact that these results were so impactful only became clear after completing the study.

Adriaan: From a wider perspective, it is our aim as a research group to improve the quality of life and life expectancy of heart failure patients. We realized that the treatment of all heart failure patients is largely similar, despite major differences in clinical phenotypes and underlying etiology. We are slowly acknowledging that we need a more individualized approach to further improve our treatment of specific groups of heart failure patients. With this study, Bernadet and her colleagues have expanded on previous research to make personalized medicine more feasible. Treating the sexes differently is one obvious form of personalized medicine.

How will this study benefit the patient?

Bernadet: This is a very common question. Unfortunately, this study was not designed in a way that will directly result in adjustments to current guidelines, since this sex-specific study was not performed in a randomized clinical trial and will not yet affect the patient. However, we do hope that this study will have some influence on future treatment and research by helping researchers realize that these sex differences can easily be studied as long as women are well represented in cohort studies and large clinical trials. The percentage of women participating in the major heart failure trials is usually only around 20%, which is not sufficient to investigate possible clinically important sex differences. I hope this study will lead to similar studies in all fields of research, and causes a major change in how future research will be designed.

You said that you could not plan for such convincing results when you started this study, but was this something you always strove to achieve?

Bernadet: No. Quite the opposite. As a high school student, I had a lot of doubts about what I wanted to do with my career. I already liked medical topics a lot, so I considered getting a degree in physical therapy, or becoming a pharmacist. I actually did not intend to enroll in medicine, but I attended an open day at the University Medical Center Utrecht and I really enjoyed it. I decided to apply for medicine a week before the deadline, albeit without truly believing that I would like it. However, like most things I start, I quickly realized that I enjoyed studying medicine and I was soon fully committed to becoming a doctor

How did you end up doing a PhD program in the department of cardiology?

Bernadet: After getting my degree as an MD in Utrecht, I worked as a junior doctor (ANIOS) at the department of cardiology at the Jeroen Bosch Hospital in Den Bosch. Working in the clinic for a year was very important to me, as it made me realize that I was really passionate about becoming a clinical cardiologist. I finally applied for a job as a junior doctor at the department of cardiology at the University Medical Center Groningen, but I quickly discovered that they had no positions. Instead, they proposed a meeting with Adriaan. I did not know who Adriaan was, but went to his office for a meeting. Adriaan described his work and the research group, and amazed me with his sincere enthusiasm, commitment, and honesty, which promptly convinced me to get a PhD. I started as a PhD candidate under the supervision of Adriaan soon after that meeting.

People sometimes say that there are no good teams, only good leaders. Adriaan, as a principal investigator, do you agree with that?

Adriaan: Well, sometimes you just have to be lucky. I value the team above everything else; even above its individual components. If you want to go fast, travel alone. If you want to go far, travel together. This is something I encourage in our group. We have a weekly group meeting every Friday morning and this is really the highlight of my week. Everyone shares their results, listens to each other, and actively participates in the discussion. This creates a great sense of coherence in the group that simultaneously allows for the individual growth of each researcher and their specific topics; which, in turn, improves the bigger picture as well. Therefore, the individuals grow as a result of the group. I would therefore like to turn this statement around; there are no good leaders, only good teams. It is essential to create a constructive environment that allows for synergistic interactions between unique individuals. If you combine this with a relevant setting that keeps the team involved in what matters, e.g. improving the lives of patients, it is only logical that the result is an atmosphere that continually motivates the individuals, who in turn continuously motivate each other. I think that is the reason why the team is the key to success.

We thank Bernadet Santema, Adriaan Voors, and Martijn Hoes for their time and efforts on preparing this interview.