Amy Dockser Marcus argues that the way we do science has changed. As evidence, she tells the story of how parents of children with a rare disease - Neimann-Pick Type C, or NPC – became partners with drug companies and NIH scientists in designing research on potential treatments for NPC. The moral of the story isn’t clear. On the one hand, these parents efficiently educate themselves about both the science and the politics of drug development in the USA. They collaborate with scientists to organize clinical trials. They learn about the ethics of biomedical research and the trade-offs between their hopes that new treatments will work and their understanding that, in order to prove that the treatments work, rigorous studies must be done. Marcus shows us how the choices faced by such parents are agonizing – should they gamble that an unproven treatment might be safe and beneficial, or should they enroll their child in a clinical trial that might not help their child but might allow future children to benefit from the results of good science.
Marcus suggests that this sort of “citizen science” is a departure from the old days when scientists, cloistered in their laboratories, decided what to study based on their own interests without seeking input or developing awareness of the issues of concern to the people whose diseases they were studying.
It is easy to like the story of “citizen science." We like to think that ordinary people are smarter than experts. The story has been told before, in movies like Lorenzo’s Oil (tagline: some people make their own miracles) and Dallas Buyers Club (tagline: dare to live!). In these fairy tales, citizens take on the heartless bureaucracy show that careful science is just a jobs program for careerist scientists and heartless bureaucrats.
The real world is more complicated. In most of these stories, including the one that Marcus tells, the drugs that citizen scientists touted did not work. In all these tales, scientists were eager to collaborate with activists if the activists were willing to acknowledge a difference between passionate beliefs and dispassionate statistics.
In the end, the supposedly inspiring story of citizen science in NPC is a tragic one. The studies that the parents helped design showed that the drugs that they hoped would be effective were neither safe nor effective. The first patients’ experiences were not good. They got serious infections and strokes. They discovered that the drug caused hearing loss. One patient got liver cancer. Some died of complications from the treatments.
In the end, the book portrays the ways that there are no shortcuts in science. Instead, the stodgy and time-consuming approaches of the scientists seem to be the only way to test whether drugs work.
The book breaks new ground in its understanding of the role of drug companies in the high-stakes game of drug development for rare diseases. It is very expensive to do the careful studies that will show whether a drug really works. The money must be spent up front, with no guarantee that the drug will ultimately be safe and effective enough to be approved by the FDA. If it is not, the companies go broke. If it is successful, they can make money.
In the case of NPC, two companies, Vtesse and CTD holdings, were studying different drugs. Vtesse did a clinical trial that enrolled 51 children. They did not publicize the results. Vtesse was then bought by another company, Sucampo, for $200M, probably with the hope that the new drug for NPC would generate revenue. Shortly after the purchase, Sucampo announced that they hoped to launch the drug for sale in 2019 (even though they did not yet have FDA approval.) A month later, though, Sucampo was bought by Mallinckrodt Pharmceuticals for $1.2B. Then Mallinckrodt announced that the trial results showed no benefit and that they would not be seeking FDA approval. Controversy continues as to whether these drugs hold promise as effective treatments for NPC
Many parents still think the drugs work. They think that their children are more alert, communicate better, and have a better quality of life. They think that the studies were poorly designed and that objective outcomes measures ignore the subjective observations of the parents.
The FDA doesn’t know what to do with such discordant views and discordant approaches to drug evaluation. They must balance the objective data with the passionate parental advocacy. An FDA Advisory Committee meeting for one NPC drug concluded that the drug didn’t work but they voted 10-3 to approve it anyway. A couple months later, FDA leadership ignored the Advisory Committee recommendation and rejected the application. The drug continues to be used off-label.
One recent review concluded that the most important interventions for children with NPC are non-pharmacological ones like regular physical activity and well-designed nutritional approaches.
Citizen science may be here to stay. Collaboration between patients, families, scientists, regulators, and marketers is essential. But there are no shortcuts in science. No matter who is doing the studies, the methods must be rigorous and the interpretations impartial. After all, even scientists are citizens. We live by the same rules.