GM SciAm0120 OnsertFinal

GOOD
MEDICINE
Health, Ethics and Innovation
a collaboration between Bioethics International and Scientific American
THE GOOD PHARMA

SCORECARD
MILLION-DOLLAR DRUGS
SHORTCUTS ON
COVID VACCINES
EQUITY &
AFRICAN GENOMES
THE NEW CULTURE OF
DATA SHARING
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22 4
[ CONTENTS ]
4 Medicine for All 14 Opinion: SCIENTIFIC AMERICAN

PUBLISHER:
Drugs are currently tested "Africans Need a Plan" JEREMY ABBATE
disproportionately on people BY JANTINA DE VRIES, ANISE N. MANAGING EDITOR,
who are young, white and male. HAPPI & CHRISTIAN T. HAPPI PARTNERSHIPS & CUSTOM MEDIA:
Technology may offer a solution. CLIFF RANSOM
BY CARY P. GROSS, MD 16 Million-Dollar Drugs PROJECT EDITOR:
FRED GUTERL
Allowing manufacturers in the U.S.
DESIGN DIRECTOR:
6 Testing for Two to set prices creates problems for JOELLE BOLT
Ethical standards now call for patients and is unsustainable for PROJECT MANAGER:
including pregnant women in drug health-care payers SARAH O’MEARA
trials, but challenges remain. BY LEAH Z. RAND & INFOGRAPHICS:
BY ANNE DRAPKIN LYERLY AARON S. KESSELHEIM KATIE PEEK
BIOETHICS INTERNATIONAL
9 When Science Sprints 20 A New Culture of Sharing FOUNDER:
The life-and-death urgency of the By making data openly available, JENNIFER E. MILLER, PHD
coronavirus pandemic has led to scientists are increasing the PROJECT ADVISORS:
heroic research efforts and some impact of medical research CARY P. GROSS, MD;
MICHELLE MELLO, JD, PHD;
ethical lapses. BY JOSEPH S. ROSS, MD CHERYL PEGUS, MD, MPH;
BY MICHELLE MELLO & JOSEPH S. ROSS, MD, MHS;
DAVID MAGNUS 22 The Good KIMBERLY A. SABELKO, PHD
STEPHEN M. SAMMUT, MBA, PHD
Pharma Scorecard
11 A Price on African Genomes To encourage drug companies
GOOD MEDICINE: HEALTH, ETHICS AND
INNOVATION IS PRODUCED FOR BIOETHICS
The scientific importance of diverse to do the right thing, Bioethics INTERNATIONAL BY SCIENTIFIC AMERICAN
genomic data has triggered intense International ranked them CUSTOM MEDIA, A DIVISION SEPARATE
FROM THE MAGAZINE’S BOARD OF EDITORS.
interest in the genomes of Africans. according to ethical practices. COPYRIGHT ©2020. ALL RIGHTS RESERVED.
BY DANIEL LEVINE BY JENNIFER E. MILLER, PHD Cover image: Maravillas Delgado
2 GOOD MEDICINE: HEALTH, ETHICS & INNOVATION
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[ LETTER FROM THE EDITORS ]
Matters of Trust
H
ippocrates, the Ancient Greek physician of-
ten called the father of medicine, might not
have foreseen the privacy issues presented
by Facebook patient groups, or the sharing
of electronic health records. Nor would the transpar-
ency of data in clinical trials have been a concern
to him or to the multitude of philosophical think-
ers through the ages and across the world who have
ruminated on the nature of medicine and the moral
responsibilities of those who deliver it.
But these thinkers would have felt right at home opportunities become more promising and dependent
at the intersection of medicine and ethics, a universal, on technology, the innovators in medicine need to
timeless concept encompassing the “heart” of health continually address the influence of the profit motive
and concerned not just with the well-being of the and the gap between the medical “haves and have-
beneficiaries of care, but the context surrounding its nots,” with the goal of building a health-care system
transparency, discovery and equitable delivery. that is as fair as possible.
With a pandemic commanding the attention of We will explore the many challenges and issues of
every stakeholder in the health-care ecosystem— trust faced by the biopharma industry, and the ways
patients, providers, scientists, policymakers, in- in which collectively we can ensure that it serves
dustry players, wor- the interests of patients everywhere. A key element
ried citizens in every of Bioethics International’s legacy work, the Good
country—the topic of How can Pharma Scorecard, an index ranking the largest
heath innovation and
the ethical framework
government and pharmaceutical and biotechnology companies and
their products on ethical standards, is presented in
through which it must industry deliver a graphically rich format.
be viewed has taken on coronavirus We are excited to bring you this timely and im-
renewed urgency. How
can government and
vaccines fairly? portant project, in the hope that it ignites a broader
discussion of the responsibility, transparency and
industry deliver corona- trust in one of our planet’s most important endeav-
virus vaccines fairly? Is ors, the pursuit of good health.
the life-sciences industry committed to safety, trans-
parency and patient-centric health care? The inter- Sincerely,
section of science and moral responsibility has never Jeremy Abbate
been more significant. Publisher, Scientific American
Exploring this critical intersection is the core
Fred Guterl
mission of Good Medicine: Health, Ethics and Innova-
@MARAVILLAS DELGADO
Project Editorial Director

tion, a debut media program and collaborative ven-
ture from the Scientific American Custom Media Jennifer E. Miller, Ph.D.
Group and Bioethics International. As medicine Assistant Professor, Yale School of Medicine
shifts from a focus on the doctor-patient relationship Founder, Bioethics International
to more complex systems of care, and as therapeutic
SCIENTIFIC AMERICAN CUSTOM MEDIA 3
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Medicine
for ALL
Drugs are disproportionately
tested on people who are young,
white and male. Technology
may offer a solution.
BY CARY P. GROSS, MD
ILLUSTRATIONS BY BRIAN STAUFFER
I
n deciding whether to un- A trial answers both questions Latinx patients. Across all clinical
dergo a certain treatment only when a patient happens to be trials for cancer, Black and Latinx
for cancer or another seri- similar to the participants in the people are less well represented
ous illness, a patient needs clinical trial. But that is often not than they were 20 years ago.
to know if it is indeed the the case. The volunteers in clinical There are several reasons for
safest and most effective trials tend to be whiter, younger, this lack of inclusion. Some sci-
option available. healthier and more likely male entific protocols explicitly exclude
A complicating factor in than real-world patients. For ex- patients who are older, sicker, or
choosing the best option is the ample, individuals aged 65 years who have functional impairments.
difference between the goals of or older account for about two For example, more than half of
the scientists who test and ap- thirds of new cancer diagnoses in randomized trials for ischemic
prove new drugs and the goals of the U.S., but less than one third of heart disease explicitly excluded
a person seeking treatment. The cancer clinical trial participants. elderly patients from enrollment,
goal of a randomized trial is to One study found that patients age mainly because they tend to have
determine whether the benefits of 75 years or older account for only serious chronic illnesses or are
the treatment outweigh its harms 10 percent of trial participants but physically frail, which constitutes
among patients who are similar made up 30 percent of patients a de facto age restriction. A simi-
to those who are enrolled in the with cancer. Women make up few- lar dynamic often results in the
trial. This is important informa- er than 50 percent of participants exclusion of Black patients, who
tion, to be sure, but the patient in studies of cancer, HIV, heart face inequities in access to health
needs to know something more disease and other conditions. A care and insurance, chronic ill-
specific: Is the treatment safer review of therapeutic cancer tri- nesses and racism that affects
and more effective for people like als from 2003 to 2016 found that how they interact with the health
me—those with similar health non-Latinx whites were far more system. In particular, inappropri-
characteristics? likely to be enrolled than Black or ate treatment of Black patients
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and research participants in the expensive and still might not offer munity is to embed clinical re-
past has contributed to a lingering a broad enough population cov- search within clinical care, invit-
mistrust of the medical profes- erage, and of course it would not ing patients in routine clinical
sion, which makes some individu- solve the enrollment problem. practice to participate in studies.
als hesitant to sign up for a trial. Technology presents us with After all, while nearly 70 percent of
The poor representation of a more realistic option: the use children with cancer are enrolled
real-world patients in trials dra- of electronic medical records to in research studies, fewer than 5
matically limits the ability of doc- gather data about drug safety and percent of adults with cancer are
tors to distinguish which patients efficacy in the real world, outside enrolled. By broadening study en-
are likely to benefit from a given rollment to many
treatment. The example of bevaci- more types of pa-
zumab, an antibody that inhibits Digital technology has led to a tients, we can ac-
the growth of blood vessels in tu-
mors, is a case in point. In a ran-
growing appreciation for the role celerate the rate
of developing new
domized trial of 878 patients with that real-world data can play in evidence. And by
advanced lung cancer, patients informing clinicians about ensuring that the
who received bevacizumab lived
12 months on average—about two
appropriateness of treatments patients in the
studies reflect the
months longer than patients in the for specific groups of patients. populations that
comparison group. About one in may be eligible
four trial participants were age 70 for the new treat-
years or older. By comparison, half trials, after regulatory approval. ment, the new evidence will be
of all patients diagnosed with lung By increasing our ability to har- much more relevant to patients,
cancer in the U.S. are older than 70 ness and analyze data, digital clinicians, and the broader public.
years. This age difference is trou- technology has led to a growing This critical issue applies to nearly
bling because an analysis of the appreciation among medical sci- all diseases. In COVID-19 stud-
224 patients in the trial older than entists for the role that real-world ies, for instance, there is already
70 years found that bevacizumab data can play in informing clini- evidence that elderly and minority
was not associated with increased cians about the appropriateness patients are being excluded.
survival—and the risk of toxic- of treatments for specific groups The importance of real-world
ity was twice as high. Of course, of patients. That is, after studies data should be evident to fans
224 patients over the age of 70 is conducted primarily in younger of sports. Every spring, baseball
a small sample size, which makes patients lead to FDA approval for teams start their training sessions
it hard to say if these results are a new drug, scientists subsequent- brimming with optimism that this
meaningful. This kind of uncer- ly explore what happens when will be the year they make it to the
tainty is commonplace for many older persons receive the drug in World Series. A team with a roster
drugs and many patient groups. routine clinical practice. full of stars might “look good on
Yet new treatments still diffuse A drawback to this approach paper.” But we don’t really know
into clinical practice: Despite this is that patients who weren’t repre- which team is best until they actu-
unfavorable benefit-to-risk ratio, sented in the controlled and well- ally compete against other teams
up to 20 percent of older patients monitored environment of a ran- —on home and away fields—over
with lung cancer were receiving domized trial will wind up being the course of a long season. By the
this treatment shortly after FDA real-world test subjects—without same token, gathering data about
approval, studies show. even knowing it; they will take drugs after they’ve reached clinical
One obvious way around this the drug before its risks and ben- practice and continuing to test them
dilemma is to build upon our exist- efits are accurately determined in iteratively, comparing treatments
ing clinical trial infrastructure— their age group. In this respect, against alternatives, in diverse pa-
that is, to keep enrolling patients this solution is not ideal, but it is tient populations, would help doc-
using the same tools we’ve always better than the current system, tors better prescribe winners.
used, largely focused in large where data is not systematically
academic medical centers—and collected once a drug is approved Cary P. Gross, MD, is a professor
simply strive to make the studies An approach starting to gain of medicine and epidemiology at
larger. This approach would be momentum in the medical com- the Yale School of Medicine.
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Testing for Two
In a seismic shift, medical ethics now
call for pregnant women to be included
in drug trials.
BY ANNE DRAPKIN LYERLY
F
36 included
ifteen years ago, the claim was audacious: base of research data. More than 25 professional or- lactation
SOURCE: MITCHELL, ALLEN A. ET AL., "MEDICATION USE DURING PREGNANCY, WITH PARTICULAR FOCUS ON PRESCRIPTION DRUGS: 1976–2008," AM J OBSTET GYNECOL., JULY 2011.
that the best way to assure the health of ganizations have come together to advocate health data
pregnant women was to make sure they policy initiatives that advance pharmacologic tri-
were included in experimental research als in pregnant and lactating women. According to
on drugs and vaccines. revised U.S. research regulations in effect January 50 included
For years bioethicists and scientists 2019, pregnant women are no longer designated as a both pregnanc
had assumed the opposite—that exposing vulnerable population. & lactation
a fetus to a drug under study was ethically unaccept- After a long battle, the question now is not data
able. Oversight committees routinely required provi- whether to do research with pregnant women, but
sions that minimized the likelihood of pregnancy in how to, ethically and efficiently, make up for so much
almost all clinical studies. They insisted on pregnan- lost ground. Many challenges remain.
cy tests and contraception. A woman who became One challenge is determining when to include
pregnant during a study had to be removed, and pregnant women in research and when to exclude
79 included
pregnancy
asked to discontinue use of the experimental drug. them. The answers depend on many factors pertain-
data
Such caution has had an unintended and harmful ing to a particular study. Some note that including a
consequence: profound knowledge gaps around the small number of women who are pregnant can add
safety and use of medications in pregnancy. complexity and cost to a study and may not yield
In recent years, however, researchers and poli- enough 414 have
data noto make useful conclusions specific to
cymakers have turned this ethical frame completely pregnancy. human data on unresolved issues include what
Other
around. They have begun to recognize that ethics do studies pregnancy
should or be conducted exclusively with preg-
not preclude research in pregnancy but rather require it. nant lactiation
women, at which point in the drug development
Organizations that offer guidance about the de- pipeline pregnancy-specific data should be gen-
velopment and use erated, and, after
of drugs are now drug approval,
Prevalence of drug use during pregnancy
offering strong how long is it ac-
(Average number of drugs taken. Prescription drugs
statements in fa- are in red; over-the-counter are in blue)
ceptable to wait
vor of including to assess safety or
pregnant women 19 76 dosing for women
and their interests who are pregnant.
in the biomedical Incentives also
© BRYAN STAUFFER (Illustration, opposite page)
research agenda. 19 92 need some atten-

For instance, re- tion. Despite the
cent draft guid- shift in ethical
20 08
ance from the reasoning, many
1 1 2
Food and Drug of those respon-
A d m i n i s t r at ion sible for drug de-
calls filling knowledge gaps about medications in velopment may still have reason to exclude women.
pregnancy a “critical public health need.” A task- Pharmaceutical manufacturers may prefer not to
force report to the Secretary of Health and Human use pregnancy-specific product labeling, which can
Services offers recommendations to advance the make them liable for any drug-related harms to the

Questions of risk are vexing. Often they involve taboos, such as any
consideration of trade-offs between maternal and fetal health.
the women or their offspring; without such label- and experience of the women for whom illness and
ing, the liable party is usually the prescribing doctor. pregnancy co-occur.
Many researchers and oversight committees tend I am optimistic that change is within reach.
to focus narrowly on minimizing risk among study Through the PHASES Project, a multi-year proj-
subjects (or protecting institutional interests) rather ect funded by the National Institutes of Health, I
than considering the interests of the general popula- have worked closely with an international group of
tion who will be administered the drugs. experts from leading research and advocacy orga-
Entrenched patterns of exclusion can persist nizations on developing guidance toward ethically
even where a study drug advancing research with
is likely to be beneficial pregnant women in the
or even lifesaving. In the context of HIV and relat-
How many drugs are tested for pregnant
2013–2016 Ebola epidemic ed infectious diseases. We
women? Figures come from FDA data
pregnant women were ex- on prescription drugs approved between have learned much from
cluded from all drug and June 30, 2015–September 30, 2017 women at risk for, or living
vaccine trials against the with, HIV. And we have
disease, even though Eb- found broad consensus on
SOURCE: "TASK FORCE ON RESEARCH SPECIFIC TO PREGNANT WOMEN AND LACTATING WOMEN," PRGLAC REPORT, SEPTEMBER 2018.
ola in pregnancy is a very many strategies that foster
grave danger (for both inclusion. For instance, re-
36 included
mother and baby). More lactation searchers should commit to
recently, pregnant women data including pregnant women
have been widely excluded in studies whenever pos-
from COVID treatment 50 included sible; oversight committees
both pregnancy
trials—even in trials of & lactation should require justification
data
drugs already widely used whenever pregnancy is on
in pregnancy for other con- the list of exclusion crite-
ditions. There have been ria; and pregnant women
79 included
appeals for inclusion in pregnancy should be guaranteed fair
both cases, which is prog- data access to trials or programs
ress, but continued efforts offering experimental life-
will be needed to ensure 414 have no saving interventions.
that pregnant women are human data on
pregnancy or Many people now are
not again left behind. lactation deeply committed to re-
Going forward, ques- dressing the evidence gaps
tions will arise about how and ensuring that the in-
to interpret and communicate data, especially about terests of pregnant women and their babies are repre-
risk. Questions of risk and
19 76
pregnancy are particularly sented fairly in the biomedical research agenda. Doing
vexing and difficult; often they involve taboos, such so is an ethical imperative; the pathway forward is be-
as any consideration of19 trade-offs
92 between maternal coming clear and beckoning more strongly than ever.
and fetal health. For the most feared outcome—med-
ication-associated birth defects—risks will take time Annie Drapkin Lyerly, MD, MA, is a professor of social
20 08
to characterize.1
Definitive estimates1
may
2
require medicine and associate director of the Center for
thousands of exposures, raising questions about how Bioethics at the University of North Carolina, Chapel
to communicate early or uncertain results; how to Hill, and research professor in obstetrics and gyne-
reassure women or doctors that a drug is safe or safe cology. She is the author of A Good Birth: Finding the
enough; and how to appropriately honor the values Positive and Profound in Your Childbirth Experience.
GM_final_SD.indd 8 11/11/20 2:48 PM

When Science Sprints
the public before they’ve been re-
viewed by experts, which can lead
to a situation in which doctors,
politicians and others advocate
unproven cures.
BALANCING SPEED AND RIGOR

The gold standard for scientific
learning is the randomized, con-
trolled trial (RCT), in which a
group of participants is random-
ly assigned to receive either the
treatment being investigated or
a comparison treatment, which
might be a placebo. Randomly as-
The urgency of the coronavirus signing participants to these two
pandemic has led to enormous groups ensures that the groups
are similar, reducing the possibil-
research efforts and some shortcuts.
ity of bias.
BY MICHELLE MELLO AND DAVID MAGNUS Although SARS-CoV-2 vac-
cines are being tested using RCTs,
nonrandomized studies have been
common for COVID-19 thera-
pies. Many have occurred with-
SOURCE: "TASK FORCE ON RESEARCH SPECIFIC TO PREGNANT WOMEN AND LACTATING WOMEN," PRGLAC REPORT, SEPTEMBER 2018.
in “expanded access programs,”

through which the Food and Drug
Administration allows patients to
access therapies that have not yet
received marketing approval. For
instance, for convalescent plasma
(blood plasma from disease survi-
vors), evidence from case reports
and animal studies was provoca-
tive enough to justify launching
an RCT to test it for COVID-19.
However, the federal government
instead approved an expanded
access program through which
physicians administered plasma
T
to nearly 70,000 patients without
any control groups. Without ran-
he COVID-19 pan- ing to the SARS-CoV-2 virus have domization, researchers have not
demic has triggered been published in academic jour- conclusively shown that improved
the biggest mo- nals in the biomedical and life sci- outcomes are the result of taking
bilization of sciences to date. plasma. Nevertheless, the FDA
entific effort in a This scientific surge is as- granted an emergency-use autho-
generation. Scien- tounding and inspiring, but it has rization for convalescent plasma
tists from fields as produced some ethical dilemmas. in August. Another cautionary
diverse as immunology and com- The urgency of the crisis has led tale is hydroxychloroquine, the
puter science quickly pivoted to to a proliferation of studies, some drug President Trump began
© JAMES FRYER
studying drivers of the epidemic of which short-circuit the most touting in March. The FDA au-
and potential countermeasures. rigorous scientific standards. Re- thorized it on the basis of obser-
More than 54,000 articles relat- sults often get disseminated to vational studies and later had to
GM_10_9.indd 9 10/23/20 6:59 PM

reverse itself when RCTs showed could post “preprints” of their PRIORITIZING STUDIES
it to be ineffective and unsafe. papers. Because journals often Even in a global pandemic, re-
Conducting nonrandomized require authors to keep papers searchers can face a shortage of
studies not only generates lower- confidential until they’re pub- patients at research hospitals who
quality evidence but can also lished—a strong disincentive to are willing and eligible to enroll
divert patients, funding, and re- share results early—the platform in clinical trials. When research
searchers’ time that might other- founders got leading journals to teams are jockeying to recruit sick
wise have been directed to RCTs. allow pre-publication dissemina- patients, who should get priority?
Every effort should be made to tion. MedRxiv and bioRxiv now The explosion of human stud-
implement RCTs during disease host nearly 9,000 papers related to ies during epidemics raises the
outbreaks. Getting them going SARS-CoV-2. These early releases prospect that lower-quality stud-
quickly requires planning be- have played an important role in ies could crowd out higher-quality
forehand. When the next strain informing pandemic responses. research, or that all trials will en-
of coronavirus appears, for ex- Scientists understand the lim- counter under-enrollment. Un-
ample, which therapeutic ap- itations of non-peer-reviewed re- fortunately, our system of human
proaches should we test and what ports—however, others may not. research oversight is not designed
should the RCT design be? Thanks to social media, preprints to prioritize among studies. We
are being circulated quickly, need a fair, transparent process in
SHARING RESULTS QUICKLY widely, and with little reflection which a multi-disciplinary com-
Is it advisable, given the urgency mittee of experts
of learning during pandemics, to that includes rep-
publicize study findings before
they undergo peer review? During
Nonrandomized studies, resentation from
disease-affected
a crisis, sharing results quickly rather than serving as an interim communities de-
can save lives or motivate other step in evaluating a potential cides whether a
scientists to pursue additional
work or abandon dead ends, but
treatment, can wind up given trial is worth
doing at a given
it can also cause rapid dissemina- supplanting the gold standard. site, what resourc-
tion of low-quality studies with es it will consume,
potentially flawed conclusions. what the cost to
Traditionally, study reports on their merits. Yet a study of CO- other research studies or clinical
aren’t made public until they VID-19 preprints later published care will be, whether there’s du-
have been submitted to a schol- in journals found that more than plication with other studies, and
arly journal, which asks experts a quarter underwent changes to whether it contributes to diversity
to critique them. Journal editors the abstracts that affected the in the overall portfolio of research
then either reject the paper or re- study’s conclusions. being pursued. Such committees
quire the authors to respond to Before physicians start chang- should be organized at universities,
questions and address reviewers’ ing their clinical care based on the federal government and the
criticisms. There may be several preprints, these papers should World Health Organization as part
rounds of back and forth until undergo at least some review by of pandemic preparedness efforts.
the editors are satisfied that the experts. The open-access jour- Among the emerging lessons of
report is ready for public con- nal RR:C19, launched in July, is COVID-19 is that getting the most
sumption. This process can take a promising vehicle. An initiative out of a scientific surge requires
months. of the MIT Press and the Univer- planning. Creating structures to
Even before COVID-19, sci- sity of California Berkeley, it pro- ensure wise allocation decisions
ence was shifting toward earlier duces expert reviews of impor- and reasonable quality control dur-
sharing of reports. In 2019, Cold tant preprints on COVID-19 in ing emergencies will pay dividends.
Spring Harbor Laboratory, Yale a few days. But it can only reach
University, and BMJ, a scientific a fraction of the many preprints Michelle Mello, JD, PhD, is a
journal company, created two being published. Researchers professor of medicine and law and
online platforms, medRxiv and have called for more scientists to David Magnus, PhD, is a professor
bioRxiv, where researchers in the volunteer for and mobilize rapid- of medicine and biomedical ethics
health and biological sciences review services. at Stanford University.
GM_10_9.indd 10 10/23/20 6:59 PM

A Price on
African Genomes
The scientific importance of diverse
genomic data has triggered intense
interest in genomic data from African
people—and created ethical dilemmas.
BY DANIEL S. LEVINE
I
ILLUSTRATIONS BY MARINA MUUN
n 2018, a whistleblower employee of the Well-

come Sanger Institute filed a complaint against
its parent organization, Genome Research
Limited, accusing the institute of seeking to
commercialize DNA samples from Indigenous
tribes in Africa in violation of ethics and of le-
gal agreements with African institutions. Of-
ficials from Sanger and life-sciences firm Thermo
Fisher had talked about developing a research tool
based on the DNA samples, according to emails ob- the DNA samples. Sanger, which declined an inter-
tained by The Times, a London-based newspaper. view request, has said that independent investiga-
The project ended shortly after the talks came tors found no breach of contract or infringement on
to light, and Sanger’s partner, Stellenbosch Univer- intellectual-property rights. But the episode brought
sity in South Africa, demanded that Sanger return into sharp relief the fears of African researchers

about the industry’s recent interest in the genomic the U.K.’s health agency, which had operated labs in
data of African people. Sierra Leone during the outbreak. But it is unclear
In recent years, scientists have come to real- who has had access to the samples. (Americans, too,
ize that studying the genomes mainly of people of worry about who has access to their medical data
European descent omits a broad range of genetic and how that data is used—anecdotal evidence sug-
variation that could be useful in precision medicine. gest that the DNA samples from COVID-19 tests are
African genomes have already helped researchers owned by the testing companies.)
understand who may be at heightened risk for de- African scientists also point to “helicopter” re-
veloping kidney disease, why some people have an searchers, who make trips to Africa to collect genet-
adverse reaction to the use of codeine, and who may ic material and return home to use it as they wish,
be most vulnerable to certain infectious diseases. So sometimes publishing without crediting scientists
far, however, European genomes account for 80 per- in Africa who may have gathered the materials. The
cent of the genetic data that’s been studied. work does not necessarily seek to answer scientific
Genomics researchers in academia and the drug questions of relevance to people in Africa, such as the
industry have recently accelerated efforts to develop role genetics plays in malaria, tuberculosis, sleeping
large sets of genomic data from Africans—libraries sickness and other diseases.
of tens of thousands of genomes—along with patient “The mistrust has built over the years,” says Am-
medical records. Analyzing large data sets is impor- broise Wonkam, associate professor and senior spe-
tant for developing new diagnostics
and therapies that would allow phy-
sicians to tailor treatments to indi-
vidual patients and provide for early “The principle should be that Africans
interventions for people at risk of de- should not just be used as subjects for
veloping certain diseases.
Medical researchers agree on the study. African scientists have to be part of
value of the science. But African re- it, and it has to be something that is for the
searchers are concerned about how
research participants are recruited
collective benefit.” —GORDON AWANDARE
and who controls the research agen-
da. These fears are shaped by the
history of colonial powers profiting from the labor cialist in the division of human genetics at the Uni-
and natural resources of the continent, as well as the versity of Cape Town. “Today when we speak about
Sanger episode. data and genetics, it’s obvious that some of the re-
“I’m concerned the genomes of Africans are going searchers within the continent, based on the histori-
to be used and exploited for good stuff, but then they cal context, will approach it with caution because
will have nothing back,” says Christian T. Happi, there is a fear of being exploited again and again.”
director of the African Center of Excellence for Ge- “The principle should be that Africans are not just
nomics of Infectious Diseases in Nigeria [see sidebar be used as subjects for study,” says Gordon Awandare,
on page 14]. director of the West African Center for Cell Biology
of Infectious Pathogens in Ghana. “African scientists
MISSING CONSENT have to be part of it, and it has to be something that
The concern is not abstract. Western firms have re- is for the collective benefit.”
cently engaged in ethically questionable practices.
For instance, thousands of blood samples from in- BIG VALUE
fected patients during an Ebola outbreak in West Although scientists are still in the early stages of ex-
Africa were sent without patients’ consent to re- ploring the genetic richness of the African genome,
searchers outside Africa, leaving researchers in the its value seems to become more apparent with each
affected countries unable to study them, according passing study. Sarah Tishkoff, founding director of
to the investigative journalist Emmanuel Freuden- the Penn Center for Global Genomics and Health
thal, who first reported on the issue for Le Monde Equity at the University of Pennsylvania, recently
and The Telegraph. The samples would be critical analyzed the genomes of 180 people from 12 differ-
for the development of treatments. Thousands of ent ethnic groups in Africa. They found 5.7 million
the samples were sent to Public Health England, mutations of genes that were not contained in exist-
GM_10_9.indd 12 10/23/20 6:59 PM

ETHICAL PATH
Recent efforts to establish ethical norms for drug
companies in dealing with study participants have
made some progress. The San Code of Research Eth-
ics may be the first ethics code created by an Indig-
enous population in Africa. It requires community
approvals for research projects, calls for researchers
working with the San people of Southern Africa to
adhere to values of fairness, respect, care, and hon-
esty. The San drafted the code after a 2010 study in
Nature, in which researchers failed to consult their
leaders about obtaining informed consent.
The paper was a turning point for the San, who
had long complained that they’d gotten no benefits
from all the attention they received. Genomics re-
searchers used offensive terms like “bushmen,” pho-
tographed breastfeeding women and children with-
out consent, ignored social customs and failed to
meet their promises to provide feedback that could
be useful for public health.
To address the complaint of African scientists
that they are often not treated as equal partners by
their non-African peers, the U.S. National Institutes
of Health and Wellcome Trust provided $176 million
ing genetic databases, many of which are expected to in funding for ten years to establish the Human He-
be found to alter the way a gene functions. redity and Health in Africa Consortium, known as
Life-sciences companies have flocked to Africa in H3Africa. The African Academy of Sciences joined
a race to collect data. 54Gene, founded in 2019, es- in 2016 and has provided an additional $12 million
tablished a subsidiary in Lagos, Nigeria. Sequencing in funding.
giant Illumina has collaborated, since 2016, with the H3Africa’s mission is to build research capac-
H3Africa Consortium to develop and provide arrays ity, scientific skills, and leadership for genomic re-
for the study of African genomes. Roche Diagnostics search to benefit the health and economy. “The idea
is investing $42.1 million to expand its facility in for H3Africa was to root the projects that would be
Cape Town, South Africa; it expects to add 300 jobs supported in Africa—that is, the principal investiga-
over three years. And the genomics company Global tors have to be African, the work needs to occur in
Gene Corp in 2018 announced a collaboration with Africa, and it would be serving the individuals of the
the University of Namibia and the Namibian Minis- continent,” says Neil Hanchard, assistant professor
try of Higher Education, Training and Innovation for of molecular and human genetics at Baylor College
a national genomics initiative that includes plans to of Medicine in Houston, who has conducted genom-
build a Center of Excellence in Genomics in Namibia. ic studies with African colleagues.
A single patient’s genetic data is worth as much The group has grown to include 94 sites in 30
as $1,700, estimates global consulting firm EY; the African countries and recruited more than 67,000
figure, from a 2019 report, is based on an analysis research participants for 51 projects. It funds re-
of deals made by consumer genetics companies. search led by African scientists and has developed
When a patient’s medical history and genomic data infrastructure to sequence, analyze, and store data
are combined, the value climbs to $5,000. The U.K.’s and samples. It also provides mentoring and training
government funded health-care system, the National for African scientists and develops ethical guidelines
Health Service, generates nearly $6.2 billion a year for conducting genomic research.
through its marriage of whole-genome sequences to “One of the things we lack in Africa is enough
© MARINA MUUN
medical records, according to EY. skills,” says Michèle Ramsay, professor in the di-
“When we speak about African genomes, we speak vision of human genetics at the National Health
about something that has considerable value,” says Laboratory Service at the University of the Witwa-
University of Cape Town’s Jantina de Vries. tersrand in Johannesburg. “That critical mass is still

small, and we need to grow it so that more people Its policy provides them the opportunity to publish
can do incredible science. H3Africa has allowed us before other researchers capitalize on their work.
to do big science in Africa.” H3Africa researchers are required to make genomic
Ramsay believes the creation of infrastructure and data available to other researchers after submitting
opportunities can help reverse a brain drain that has data to a repository, but they are granted up to 23
scattered African talent around the world. The con- months to do so, compared to six months for most
sortium has supported the bioinformatics network NIH-funded research.
H3ABioNet, which has nodes in 16 African coun- While H3Africa has accomplished much, it can’t
tries; the African Center of Excellence for Genomics match the big money that multinational pharmaceu-
of Infectious Diseases in Nigeria; and the U.K.-based tical companies bring to bear. But it doesn’t neces-
Malaria Genomic Epidemiology Network, which has sarily have to. Its goal is not only to attract commer-
a presence in 23 African nations. “For decades, if you cial investment but also to maintain control over the
wanted to be part of big science projects, you literally research agenda.
had to leave the continent,” says Ramsay. Now, “you Some outside investors seem to be heeding local
don’t necessarily have to go to Europe or America. concerns. Adjuvant Capital, a venture capital firm
H3Africa has taken steps to ensure African scien- whose limited partners include the Bill & Melinda
tists lead research and get credit for their work. For Gates Foundation, the Global Health Fund, and No-
one, it only funds projects led by African researchers. vartis, led a $15-million venture round in April for
[ OPINION ]
“Africans Need a Plan”

N
inety-nine percent of the
revolutionary history of
BY JANTINA DE VRIES, ANISE N. HAPPI & CHRISTIAN T. HAPPI humans is contained in
the genomes of African
people. In the search for medicines
and vaccines and to fulfill the
potential of precision medicine to
tailor treatments to individuals,
Africa holds the key.
The value of this data is not lost
on pharmaceutical companies and
their investors. In 2018 Goldman
Sachs forecast a $5-trillion global
market for genomic medicine.
It’s good that the world is be-
ginning to appreciate the genetic
richness of Africa. But researchers
on the continent are becoming
increasingly concerned about ex-
ploitation. If history is anything to
go by, the quest to mine Africa’s
data will produce a few winners
and many losers.
The companies and funding
agencies often cast their motives
in humanitarian terms: their work
will help alleviate the genomic data
© MARINA MUUN
inequity gap. They make promises

that the benefits of genomic re-
search will accrue to the Africans
who participate and to their com-

54Gene, which is building a curated genomic data set to clean water and proper sanitation facilities and 20
from African populations. The company launched the percent of children in Nigeria die before the age of five.
African Center for Translational Genomics, an initia- Ensuring research data and findings are shared will
tive that brings together top researchers in Nigeria to help to identify medication risks tied to genetic varia-
collaborate on high-impact studies for publication. tions and help make better diagnostics available. The
World Economic Forum’s Leapfrogging with Precision
HEALTH BENEFITS Medicine project is working to help low-to-medium
Ensuring that Africans share in health gains that re- resources put policy frameworks in place for this new
sult from genomics research is a more difficult problem medicine but acknowledges there is a mismatch be-
than developing research infrastructure. If new diag- tween costs and available resources that limit access.
nostics and therapies from genomics remain unafford- The dearth of resources makes it all the more
able to Africans, new discoveries won’t benefit them. critical that Africans share in the benefits of the ge-
African nations continue to struggle with a lack of nome revolution. Says University of Cape Town’s de
modern health-care facilities, a shortage of medical Vries: “We need to think about the innovation chain,
professionals, and low levels of government spending about where value is rewarded, and how we do these
on health. In Sierra Leone there are only 22 physicians things in a way that is more just.”
for every million people. In the Democratic Republic of
Congo, less than a quarter of the population has access Daniel S. Levine is a freelance journalist.
Researchers on the The first step is for African cedures and public information
academics involved in genomics about the value of one’s genome,
continent are becoming research, including those in the Af- such arrangements could perhaps
increasingly concerned rican diaspora, to forge a blueprint be done ethically.
about exploitation. for rules and regulations. Most Efforts to collect African DNA
important is to establish benefit- and use it for research should in-
sharing arrangements with com- clude investment in African na-
munities. Groups like the World panies that collect African data. tions, so that they can develop
Economic Forum have been work- These could be crafted along the their own industrial and research
ing with governments and others lines of the United Nations’ Nagoya capacity. These investment efforts
on ways to regulate this activity. Protocol, which provides guidance must lead to sustained social ben-
We are skeptical. What’s been on benefit-sharing agreements for efit for the countries involved.
missing is a broad societal debate people using a country’s biodiver- Public trust is a key component
about the ethical use of African ge- sity but does not pertain to human in supporting the genomic revolu-
nomic data by private companies, samples and data. Guidance on li- tion. Our task is to ensure that profit
most of them funded from abroad. censing agreements should be in is used to create the world we want
Africans need a plan to pre- place before companies can collect to see, not the world as it is.
vent exploitation. That is a major or use African genomic data. These
goal of H3Africa, the non-profit should include provisions to ensure Jantina De Vries is a professor of
research consortium. We have that any products or therapeutics bioethics at the University of Cape
worked for several years to devel- developed on the basis of African Town. Anise N. Happi is a lecturer
op an ethical infrastructure for ge- genomic data will be made avail- in the department of veterinary
nomic research in Africa, including able to African patients at a reason- pathology at the University of
proposals for agreements about able cost. Ibadan in Nigeria. Christian T.
how profits generated from own- We need to develop creative Happi is director of the African
ing, trading or using African ge- ways of ensuring that African Center of Excellence for Genomics
nomic data should be redistributed people benefit directly from the of Infectious Diseases (ACEGID) at
to benefit African individuals and use of their data. One bold idea Redeemer’s University in Ede. This
their societies. Many of the compa- is to ensure that individuals can article represents the opinions of
nies and organizations are trying to market or sell their genomic data. the authors and not those of their
circumvent these efforts. With strict guidelines, vetting pro- various institutions or H3Africa.
GM_10_9.indd 15 10/23/20 6:59 PM

GM_10_9.indd 16 10/23/20 6:59 PM

Million-Dollar Drugs
Allowing manufacturers in the U.S. to set prices creates problems for patients and
is unsustainable for health-care payors.
T
BY LEAH Z. RAND AND AARON S. KESSELHEIM | ILLUSTRATION BY DAVIDE BONAZZI
he U.S. spends more on drugs than In many cases, such uncertainties make it diffi-
any other country, in absolute terms cult to evaluate the benefits of a drug. For example,
and per capita. Early prices of some the evidence on remdesivir, which is being used to
brand-name drugs have reached treat patients with severe COVID-19, suggests that
shocking heights—some have topped the drug reduces the time to clinical recovery by
$1 million for a course of treatment— five days without a significant effect on mortality.
and price increases tend to rise faster However, Gilead, the manufacturer, set the price at
than the rate of inflation. $3,120 per course of treatment, which is less costly
High drug prices create ethical dilemmas—espe- than five days of hospitalization. But it is not clear
cially in a pandemic, when the nation’s vast inequities that the drug actually reduces hospitalization peri-
in health care have taken on a new urgency. The fate ods. In fact, some patients with COVID-19 reported-
of millions of Americans now rides on new treatments ly are staying in the hospital longer to complete their
for COVID-19 and the prospect of effective vaccines. courses of this intravenously administered drug.
The more they cost, the harder it is for people to have A similar uncertainty has arisen in gene therapies
access to them. High prices also require patients, in- such as onasemnogene abeparvovec-xioi (Zolgens-
surers, and governments to make challenging choic- ma) for spinal muscular atrophy, which is listed at
es in how to spend limited health-care resources. $2.1 million per patient, and voretigene neparvovec-
Determining when a price is appropriate for a new rzyl (Luxturna) for a form of inherited blindness,
brand-name drug involves three fundamental ques- which is listed at $850,000 per patient. Short-term
tions: is the drug worth it, is it affordable, and is the trials of the drugs suggest that they offer important
price fair? Let’s take them one at a time. benefits to patients with the conditions they treat,
The first principle of drug pricing is that a price which is what led to their approval. But there is no
should align with the value a drug provides—the evidence yet that the effects will be long-lasting.
benefit to patients and to health-care systems. Many So far U.S. payors generally cover these prices
countries determine whether a drug is worth its for gene therapy because they are indicated for rare
price by subjecting it to a process
of evaluation to see whether the
SOURCE: DRUG LABELS AS RECORDED AT THE U.S. FOOD & DRUG ADMINISTRATION.
How Do Drugs Compare on Costs? In treating spinal muscular atrophy,

benefits are proportional. Such a dose of Zolgensma is expensive, but only one is needed; Spinraza is
health-technology assessments cheaper but requires repeating a dose every three months.
in Germany, for instance, have
helped reduce prices. Drug cost
0 $1 million $2 million
The U.S. does things differ- Zolgensma: One dose needed
ently. Many Americans tend to $2.125 million
Spinraza: Administered every three months
assume that markets will lead to
prices that reflect willingness-
to-pay, or the value of a good to Four doses Then, three Treatment with Zolgensma
administered doses per year costs as much as 27 years of
someone. But drugs are different in month one henceforth treatment with Spinraza.
from most consumer goods. New
drugs are invariably protected
by numerous patents, which give the manufactur- diseases. But as more gene therapies are discovered
ers market exclusivity. They have few constraints on for other conditions, the burden on health-care re-
how high they can set prices. Drugs are prescribed sources will quickly become unsustainable. Gene
by doctors (meaning consumers often don’t lead the therapies priced like onasemnogene abeparvovec-
decision making) and, for the majority of U.S. pa- xioi for just 1 percent of Americans would cost $3
tients, are paid for by insurance companies. trillion—as much as all current spending on health

KEY $2.125 million
Approval date and prices: Zolgensma
U.S. A rare genetic
E.U. (prices where available) muscular
atrophy disease
Type of disease the drug treats:
Inherited condition
Cancer
Not pictured: two gene therapies
approved by China in the early 2000s.
SOURCES: "APPROVED CELLULAR AND GENE THERAPY PRODUCTS," U.S. FOOD & DRUG ADMINISTRATION (U.S. APPROVALS); "GENE THERAPY MEDICINAL PRODUCTS," PAUL-EHRLICH-INSTITUT (EUROPEAN APPROVALS).
Glybera* Imlygic Strimvelis Luxturna Zynteglo Tecartus
A rare liver disorder A type of A disease causing severe A rare form of A genetic blood A type of
melanoma immunodeficiency blindness disorder lymphoma
€1.0 million
Kymriah Yescarta
Types of Types of
lymphoma lymphoma
$850,000
Gene therapy drugs
€594,000
introduced in the U.S.
and Europe since 2012
As more gene therapies $475,000
€320,000
are discovered, the €320,000 $373,000 $373,000
burden on health-care
resources could become
unsustainable. €55,000
2013 2014 2015 2016 2017 2018 2019 2020

*Glybera’s developer removed it from the market in 2017 due to lack of demand.
care. While there may be conditions for which gene on a reasonable pricing structure as a condition for
therapy offsets other medical spending, there is dis- receiving billions of dollars in grants for vaccine de-
agreement over how much of the resulting economic velopment and testing? So far it has avoided the issue
benefit manufacturers or society should be able to in deliberations over vaccines.
absorb, particularly in cases when taxpayer funding High-priced medicines can also exacerbate health-
was a key driver of the discovery of the treatment. In care inequities. For a drug like sofosbuvir, limitations
such cases, drug prices should better align with their in Medicaid that were designed to control costs could
value, and if prices nevertheless remain high, they end up widening the disparities between Medicaid
could be made dependent on the success of the treat- patients and those with private insurance plans.
ment, with payments stretched out over time, rather Taking budgets into account when negotiating a
than in a single up-front payment, and designed to price is reasonable. The Institute for Clinical and Eco-
end if the treatments stop working. nomic Research (ICER), an independent organization
The second question is whether a drug or thera- in the U.S. that
py is sustainable. Even when a drug is highly effec- assesses the value
tive and offers good value for its price, it may still of some expensive
be unaffordable to the health-care system. This was
The fate of drugs, considers a
the case with antiviral treatments for hepatitis C vi- millions rides on drug’s impact on
rus infections. Sofosbuvir (Sovaldi) was considered new treatments budgets, which is
cost-effective even at its launch price of $84,000 per important in set-
course of treatment because it offered a high cure and vaccines for ting policies that
rate. Because hepatitis C is so prevalent in the U.S., COVID-19. ensure access to
such a price would overwhelm payors like Medicaid them. More U.S.
that cannot afford to treat all of its patients with- payors, includ-
out neglecting other medical needs. Money spent ing the Veterans Administration, New York’s Med-
on sofosbuvir is money that is not available for other icaid program, CVS, and some private insurers,
health-care needs or budget priorities. This issue may have reportedly started collaborating with ICER to
also arise when a COVID-19 vaccine is approved, integrate its reports into their price negotiations.
because successful management of the virus will re- As federal, state, and private health-care payors
quire widespread administration of it. Should CO- consider the introduction of COVID-19 vaccines or
VID-19 vaccine manufacturers be able to set their widespread treatments, their impact on budgets is
own prices? Or should the federal government insist an important consideration. Since these drugs will
GM_10_9.indd 18 10/23/20 6:59 PM

How the public pays Financial Input (investment, purchases) During drug
for a new drug: Funding development
a
Gr snt
to develop Kymriah, a
Inv
cancer treatment, comes rch es
tm
indirectly from taxpayer National University ea Novartis en
Institutes research t
s
support of the National (drug company)
Re
of Health
s
labs
es
Institutes of Health
Re
Tax
sea
and investor support
rch
of Novartis, the drug
company. The public
contributes again
THE PEOPLE KYMRIAH INVESTORS
through insurance
co-payments and
Insur
premiums.
anc
Pr
e
of
pr
ts
i
i
iu of
e
en
t
ms m Pr
P ay es
Health as
Insurance ch Novartis
Co r
-pay pu
s and out of pocket
Once drug is
on the market
be used by virtually the entire population, even low While these are promising developments, action on
prices can have a significant budgetary impact. the federal level will be needed to support the states
The third key question is whether the price of a and extend these principles to Medicare, which cov-
drug is fair. Manufacturers in the U.S. have argued ers about one-third of U.S. prescription drug spend-
that they should be able to recoup the cost of devel- ing. President Trump promised such reforms during
opment and production and be compensated appro- his 2016 campaign but dropped them after confer-
priately for risks in up-front investment. In recent ring with pharmaceutical-industry lobbyists, only to
years, however, public institutions have branched issue executive orders in July aimed at curbing high
out from supporting basic and translational science drug prices that have yet to take effect (and are de-
to paying for later stages of drug development. About signed to only have a limited impact if they do). The
a quarter of new drugs approved by the FDA in the most advanced effort thus far has been the Elijah
past decade had late-stage connections to publicly E. Cummings Lower Drug Costs Now Act, passed
funded institutions. For example, one of the first by the House of Representatives in late 2019, which
CAR-T therapies approved to treat cancer, tisagen- would allow Medicare to negotiate prices for the
lecleucel (Kymriah), was developed in a collabora- most expensive brand-name drugs leveraging value
tion of Novartis and the University of Pennsylvania, determinations made in other comparable high-in-
which received more than $200 million in taxpayer come countries around the world.
funds for the research. Given the substantial public The U.S. practice of allowing manufacturers to
investment, is the launch price of $475,000 fair? In set prices creates problems for patients and is un-
the development of remdesivir for COVID-19, the sustainable for health-care payors. Recent changes
federal government supported the key pivotal trial at the federal and state levels are a first step in better
that showed its efficacy and its emergency-use au- aligning benefits and costs.
thorization. Even though the government invested
in the drug and took significant risks in its develop- Leah Z. Rand is a postdoctoral fellow and
ment, it played no significant role in setting its price. Aaron S. Kesselheim is a professor of medicine at
Efforts have been underway in the U.S. to inte- Brigham and Women’s Hospital and Harvard Medical
grate these three key principles into systems of drug School. They are consultants to the Massachusetts
© DAVIDE BONAZZI
pricing. New York, Massachusetts, Maine and other Health Policy Commission on its prescription drug
states have adopted drug affordability boards to as- price review process under a contract to Brigham and
sess drug value and help state insurance programs Women’s Hospital but do not receive personal funding
better negotiate fair prices with manufacturers. for this work.
GM_10_9.indd 19 10/23/20 6:59 PM

A New Culture
of Sharing
By making data openly available,
scientists are increasing the
impact of medical research.
BY JOSEPH S. ROSS, MD
ILLUSTRATIONS BY MARAVILLAS DELGADO
E
ach year scientists at hospitals and uni- nize that encouraging the sharing of clinical research
versities around the world start hundreds data presents an opportunity to advance medical sci-
of thousands of clinical studies involving ence and improve the integrity of research.
millions of patient volunteers and generat- As a result, the culture of science has begun to
ing vast data about the effect of new treat- shift. Scientists strip their research data of names
ments for myriad diseases. and other information that would identify specific
The trouble with this system is that more than half patients and make it available to others. They can do
of the studies are never published, and those that are it directly, when one scientist writes to another and
are often incomplete, selectively reporting favorable asks for a copy of the data. Or they can do it indirect-
outcomes and rarely reporting relevant safety find- ly, by depositing their data on a server from which
ings. In recent years, researchers have come to recog- others can download and use it.
GM_10_9.indd 20 10/23/20 6:59 PM

Data sharing marks a significant departure from of Health now shares data from its largest studies,
tradition. Scientists have often been reluctant to give which include those examining treatments to control
away the fruits of their hard work. Many spend years blood pressure, heart attack risk, and depression.
planning and executing their studies, painstakingly The Centers for Disease Control and Prevention col-
collecting and curating the data for analysis, and lects survey data from individuals throughout the
then preparing a summary report to publish. How- U.S. each year with the express purpose of sharing
ever, the advantages of data sharing are becoming so it with the wider research community. Many large
apparent that this reticence is beginning to evaporate. pharmaceutical companies similarly share clinical
Sharing increases the amount of knowledge research data collected as part of studies to deter-
that scientists can draw from available data, with- mine whether their products are safe and effective.
out having to go through the expense and trouble For instance, multiple companies share clinical
of organizing new trials. For instance, scientists can trial data through the ClinicalStudyDataRequest
re-analyze data from prior studies and use them to initiative for outside investigators to request and
explore new questions concerning safety and effica- use the data for their own research, while Project
cy or to draw new conclusions about Data Sphere is an open-access
specific subgroups of patients. Some- platform on which companies
times data from many different stud- share clinical trial data from
ies can be collected and combined for the placebo arms of their can-
larger studies. Sharing can cer clinical trials. The Good
Sharing can improve the integrity improve the Pharma Scorecard [see page
of scientific research by encouraging 22] recognizes companies who
multiple examinations and interpre- integrity of share data and encourage oth-
tations of any given research data- scientific ers to do the same.
base. This could protect help against
faulty analyses and contribute to
research. In 2011, we developed a
platform for responsible data
the verification, refinement, or refu- sharing known as the Yale
tation of prior work. Furthermore, Open Data Access (YODA)
sharing helps researchers position clinical trial data Project. We have partnered with Johnson and John-
as a public good, a resource for many to use and son and others to promote the sharing of clinical
learn from. research data for investigators based in academia,
Sharing can also make better use of limited sci- government, or even at other companies. At present,
entific resources, minimizing duplication in data researchers throughout the world have used data
collection, which reduces research costs and lowers from more than 400 trials in more than 150 proj-
the burden on patient volunteers. ects, many of which make use of multiple trials at a
Patients who volunteer to participate in research time. These studies have been used to inform clinical
studies seem to have few qualms about researchers practice recommendations and World Health Orga-
sharing data. In a recent survey of 771 participants nization guidance.
in trials in the U.S., 82 percent said they were likely The YODA Project has enabled numerous studies
to allow their data to be shared with scientists at that might not otherwise have been feasible, gener-
for-profit companies and 93 percent felt the same ating new knowledge and contributing to the clini-
about sharing with university scientists. Certainly, a cal and scientific community and informing clini-
significant number of patients worry about privacy— cal practice. The same is no doubt true for the other
about a third expressed concern about data being data-sharing platforms. While these platforms took
used for marketing purposes and 30 percent worried a great deal of time, effort, and resources to launch,
about data being stolen. But in my experience, many this investment will pay off over the next decade as
patients also understand that one group of research- scientists draw new insights from clinical trial data.
ers may have different ideas, or approaches, than the Before, only one group of investigators would use
original group of researchers, allowing them to learn data from a trial. Now, one study can inform many
new things from the same data, and prefer that their investigators, each with their own point of view and
data can be used for research by as many scientists their own goals for advancing science.
as possible.
Numerous data-sharing initiatives have been Joseph S. Ross, MD, MHS, is a professor of medicine
started in recent years. The U.S. National Institutes and public health at the Yale School of Medicine.
GM_10_9.indd 21 10/23/20 6:59 PM

The Good Pharma Scorecard
To find out if drug companies are trustworthy, Bioethics International, along with
researchers at Stanford and Yale, ranked them according to their ethics practices.
M
BY JENNIFER E. MILLER, PHD
ore than a decade ago, I was The general public certainly did not hold phar-
alarmed by the high number maceutical companies in high regard, a condition that
of ethics scandals involving has only deteriorated since. The industry is perceived
pharmaceutical companies as the least socially responsible sector in health care.
documented in the media and In some polls, drug companies rank just ahead of
the scholarly literature and tobacco companies and behind Wall Street in per-
hashed out in court cases and ceived honesty, ethics and trustworthiness. Nine
settlements. It was hard to know what to make of in 10 Americans think drug companies put profits
these reports. Were these ethics failures those of a before people; only 20 years ago, these firms were
©MARAVILLAS DELGADO
few rogue companies or employees? Had the under- among the most esteemed and respected. (Frankly,
lying issues been resolved? Or, did they constitute large institutions in general are facing growing dis-
genuine widespread problems and risks for patients? trust, from regulators like the FDA to the media and
I found myself wondering, are drug companies trust- political systems. Notwithstanding, the pharmaceu-
worthy, patient-centered, and socially responsible? tical sector is disproportionately distrusted.)
GM_10_9.indd 22 10/23/20 6:59 PM

Determining whether drug companies are trust- Where to Start?
worthy and fixing any ethics problems is an urgent The journey began by first mapping the chief ethics
public health matter. Access to medicines that are concerns about drug companies. Some companies
safe and effective is an important determinant of were accused of hiding unfavorable data to make
health. When you think about new medicines, you drugs appear safer and more efficacious. There were
have to think about the pharma industry, which concerns, backed up by research, that doctors, for-
sponsors most of the clinical research for new medi- mulary decision-makers, the Food and Drug Ad-
cines in the U.S. We cannot afford for such a major ministration, patient groups, and medical educators
player in health care to be rife with problems or dis- were in the pocket of industry. Cases of companies
trusted. When patients don’t trust drug companies, bribing doctors with envelopes of cash were making
they may be less likely to participate in clinical trials, the news. Experts accused drug companies of wast-
take prescribed medicines and get vaccinated. For ing money on marketing rather than researching
the sake of people’s health, we have to get this right. and developing new drugs. Drugs were becoming
This was the start of a journey that ultimately increasingly unaffordable.
led to the Good Pharma Scorecard (GPS), a rank- The next question was, should we tackle drug
ing of pharmaceutical companies on how well they prices or marketing practices? I wanted to break off
implement good ethical practices. The GPS helps a piece of the problem that was not only important
bridge asymmetries of information about the ethical for public health but also ripe for reform.
performance of the industry. It also recognizes best We decided to tackle two issues: how well drug
practices and catalyzes reform where needed. companies make the results of clinical trials avail-
Since my colleagues and I at Bioethics Interna- able to the public and the medical profession (trans-
tional, Yale School of Medi- parency), and how well they
cine and Stanford Univer- share the underlying data
sity put out the first GPS BEI has assessed thousands gathered during their tri-
in 2015, it has had a mea- als (data sharing). In other
surable positive effect on of clinical trials that enrolled words, whether compa-
drug companies’ practices. more than a million nies are honest, truthful
Across all metrics, the in- and transparent about the
dustry has improved year
participants safety and efficacy of new
after year, which suggests around medicines and vaccines. My
a steady improvement in the world. colleagues and I reviewed
medicines and vaccines
ethical practices. More-
over, many large compa- approved by the FDA in
nies immediately improve 2012 for HIV, tuberculosis,
practices, every year, upon breast cancer, rare diseases,
receiving our recommendations on how to tighten pediatric meningitis and many other conditions.
their procedures, bringing them up to higher ethical We were not reassured by what we found. Only
standards. Many also use their GPS results in their one in five drugs had public results for all the clinical
annual reports, which itself creates an incentive to trials supporting its FDA approval, when assessed a
improve year over year. Health-care investors, espe- year after approval. For half of reviewed drugs on the
cially those concerned with social responsibility, have market, the results of at least one phase 2 or 3 trial
begun to use the GPS in their Environmental-Social- were unavailable to the public. (Phase 1 trials test a
Governance analyses. It has been hopeful to see many drug’s safety, and phase 2 and 3 trials test its efficacy.)
multi-national large companies changing nimbly and Overall, only a median of 65 percent of clinical trial
quickly, and tracking their progress year after year. results supporting FDA approval of each reviewed
To date, BEI has assessed thousands of clinical drug were publicly available a year after approval.
trials that enrolled more than a million participants Improving transparency, we realized, was critical
around the world. We used this data to publish GPS for science, patient care and public trust. Doctors
rankings in 2015 and 2017. In this issue we are pre- need valid and objective clinical trial information to
senting the results for 2019, the third round of data prescribe the right drug for the right patient at the
we gathered. But first, I want to explain how we ar- right time. Patients, as partners in their own care,
rived at the Scorecard as a vehicle for encouraging need it, too, to make informed treatment decisions.
pharma to follow good ethical practices. If trial results are hidden, the whole ethics of a trial
GM_10_9.indd 23 10/23/20 6:59 PM

come into question, and so does the quality of our with the best social responsibility reputation, when
medical evidence. (To be fair, this is a problem in re- quality, service and price are uniform.
search generally, not just industry-funded research.) As I mulled the merits of ratings and rankings,
I started noticing them everywhere. My mother
Why We Chose a Scorecard wouldn’t buy a loaf of bread unless it had the Ameri-
Once we had decided to address transparency and can Heart Association’s heart-check trademark on the
data sharing, we needed to determine the best way packaging. My father was trying to obtain ISO certi-
to help improve industry practices. Passing new laws fication for his company. Was Mom’s AHA-certified
takes a long time; plus, we had already seen that laws bread really healthier? Would Dad’s company truly
were not being adequately monitored and enforced. improve its practices for the sake of certification?
Instead, we looked for a tool that could help us cata- I reviewed 75 rating programs (including car safety
lyze the change we felt was needed across the indus- ratings and fair trade food labels) to understand their
try. We wanted to give drug companies an incentive promises and pitfalls. I also reviewed the scholarly lit-
to adopt better practices and help us track and com- erature for evidence of efficacy of these programs, or
municate their progress over time. lack thereof, and best practices. There seemed to be
I noticed that almost every industry has some type enough evidence to support building a ranking sys-
of accreditation, certification or rating, and that these tem to measure and improve the ethical performance
programs are associated with im- of pharmaceutical companies. The
proved quality and firm performance. Susan G. Komen Foundation offered
We learned that health care was one Most hospitals seed funding and Harvard University
of the first to adopt such programs. were meeting a fellowship grant to run a pilot test.
In 1910, Ernest Codman, a surgeon at I enlisted a multi-stakeholder
Massachusetts General Hospital and
or exceeding team of advisors through Bioethics
a faculty member of Harvard Medical standards, an International, a nonprofit I founded in
School, and his colleagues developed illustration of the 2005 to help improve ethics and make
a set of hospital standards related to health care more patient-centric. We
patient safety. When he conducted old saw, “what developed standards and a scoring
on-site inspections of 692 hospitals, gets measured, system for evaluating each pharma-
he found that only 13 percent met the ceutical company’s ethics, based on a
standards. This finding was so em- gets done.” rigorous process that included review-
barrassing to the health-care estab- ing recommendations from expert
lishment that the list of failing hospitals was burned bodies and multi-stakeholder consultation.
to keep the press from finding out. Because we wanted our ranking to have an im-
Within five years, however, most hospitals were mediate impact, we built in a 30-day amendment
meeting or exceeding the standards—a prime il- window to give companies an opportunity to raise
lustration of the old saw, “what gets measured, gets their scores. By the end of the 30 days, if a company
done.” The potential to earn society’s trust, the threat could demonstrate that it had improved its policies
to a company’s reputation, the knowledge that other and practices, BEI would recalculate its score based
organizations are performing better, opportunities on this new information and publish a pre and post
to learn and refine beliefs about previously unob- score. A company would be included in a particular
served qualities—all these factors make rankings an year’s ranking only if it had a novel drug approved
effective way to prompt companies to change. Res- that year. After successfully piloting the GPS with
taurant rankings, for instance, led to significant im- the Edmond J. Safra Center for Ethics at Harvard
provements in cleanliness and, in turn, a reduction University, Arnold Ventures generously awarded us
in hospitalizations for foodborne illnesses. Consum- a large grant to scale the GPS from a pilot to an in-
ers are also more likely to patronize an institution dustry-wide annual global ranking system.

Transparency ranking
“Our ongoing commitment to # 1 Novo Nordisk 100%
data transparency is centered
on our patients and our focus to # 1 Roche / Genentech 100%
drive science forward.”
—Julia Galperin, global head and # 3 Novartis 99%
data-sharing officer, Roche
# 4 Merck 93%
# 5 Bristol-Myers Squibb 92%

“Adopting a transparency
policy that goes beyond
# 5 Pfizer 92%
global legal requirements is in
line with our core values.”
# 7 Gilead 91%
—Merete Jørgensen, senior
trial disclosure director,
# 8 Johnson & Johnson / Janssen 90%
Novo Nordisk
# 9 AstraZeneca 83%
# 10 Valeant 63%
# 11 Amgen 56%
# 12 Allergan 47%
Transparency
The GPS transparency rankings look at three tiers FDA approval of their drugs. Further down the list,
of standards. The baseline is whether a company is Allergan and Valeant Pharmaceuticals jumped up
following current laws in reporting. (Being legally in the rankings compared to their performance
compliant is no small thing: too many companies in the 2017 rankings. (Valeant has been renamed
fall short of this standard.) The middle tier asks if Bausch Health.) Gilead Sciences and Johnson &
a company is disclosing the protocols and results Johnson (J&J) fell in the rankings from 2017. A
of all the clinical trials conducted with patients company can fall in the rankings for many reasons.
to gain FDA approval of their drugs. The third Sometimes its product will rely on older studies that
tier asks if the company makes all data about the date to a time when standards of transparency were
patients who participate in a trial available to re- less rigorous. Sometimes it will acquire a smaller
searchers who request it (while observing patient company that hasn’t been adequately reporting tri-
privacy and consent). al results. Anecdotally, executives have shared pri-
In the latest GPS, only two companies scored vately that, as a result of the GPS evaluations, their
100 percent on all three measures: Roche and Novo companies now stipulate as a condition of an acqui-
Nordisk. Both companies disclosed the results for sition or merger that all transparency problems are
all of the trials conducted in patients that support fi xed ahead of time.
GM_10_9.indd 25 10/23/20 6:59 PM

Data-sharing ranking
# 1 Johnson & Johnson / Janssen 100%
# 1 Novartis 100%
# 1 Novo Nordisk 100%
# 1 Roche 100%
“A big part of leadership
is being open and clearly # 5 Bristol-Myers Squibb 80%
disclosing what we do and
the results of clinical trials.” # 5 Gilead 80%
—Laura Hagan, executive
director in the chief medical # 5 Merck 80%
office, Novartis
# 8 AstraZeneca 78%
# 9 Pfizer 75%
Yale’s YODA project “serves
as an independent, third-party
# 10 Amgen 66%
reviewer of external requests
for access to data from clinical
# 11 Allergan 59%
trials.” —Karla Childers, senior
director of strategic projects,
# 12 Valeant 14%
Johnson and Johnson
Data Sharing to facilitate widespread data sharing among the in-

Drawing on recommendations from several expert dustry (ClinicalStudyRequest.com); it was not in-
bodies, including the Institute of Medicine (now cluded in the 2019 rankings because it didn’t have
known as the National Academy of Medicine), and any new medicines approved that year but scored a
consultations with patients, industry, academics, reg- 100 percent on data sharing in the 2015 rankings.
ulators and others, the data-sharing rankings evalu- Roche, another consistent performer, has kept pace
ate whether companies provide others access to anal- with evolving data-sharing standards, as has Novo
ysis-ready participant-level data sets and clinical study Nordisk, which initially took a unique approach to
reports (CSR) for trials, within six months of FDA data sharing: It shared data directly on its website,
approval or 18 months of a trial’s completion. (CSRs allowing researchers to download them without any
contain a study’s protocol, case record, and statisti- intermediaries or other hoops.
cal analysis plan, among other information.) We also Novartis did not initially get a top score. It was
evaluate whether companies transparently disclose deficient in one respect: it had made a public com-
how many data requests they receive and how each re- mitment to share data after drug approval, but only
quest is handled (i.e., granted or denied). In 2019, four if a trial’s results were published. Since results from
companies achieved top scores in the GPS data-shar- many trials are never published, this could create a
ing ranking: J&J, Novartis, Novo Nordisk and Roche. loophole of sorts and a gap in data. Novartis used
J&J was one of the first companies to commit the GPS 30-day amendment window to close this
to sharing patient-level data and helped develop a gap and commit to sharing data for approved medi-
platform called the Yale University Open Data Ac- cines regardless of whether a paper is published on a
cess (YODA) Project. GlaxoSmithKline was also an clinical trial—joining its peers in committing to high
early adopter, having helped create infrastructure ethical standards in research transparency.
GM_10_9.indd 26 10/23/20 6:59 PM

Combined scores for all three Good Pharma rankings to date
100% 100% 97% 96% 96%
GSK NOVO NORDISK JOHNSON & JOHNSON ABBVIE BRISTOL-MYERS SQUIBB

/ JANSSEN
96% 95% 92% 90% 88%
NOVARTIS CELGENE PFIZER MERCK SANOFI / GENZYME
87% 86% 82%

71%
57%
ASTRAZENECA ROCHE / GENENTECH GILEAD BAYER VALEANT
KEY
56% 55% 2015 avg. (2015-2019)
2017 no data
2019
AMGEN ALLERGAN
Scores are based on companies’ transparency practices in developing

drugs for market. Bioethics International has published three scorecards,
but not all companies are included in each.
The Scorecard’s Impact

The pandemic has underscored the importance of
data sharing in maintaining public trust in drug
As a result of the
development and for public health. In the race to de- GPS evaluations, some
velop COVID-19 therapies and vaccines, drug com- companies now stipulate as a
panies have been inconsistent in their data-sharing
practices, and regulators have been criticized for condition of an acquisition or
some of their decisions. This lack of transparency and merger that all transparency
the deterioration in public trust could make people
reluctant to get vaccinated against coronavirus. Data
problems are fixed ahead of time.
sharing may help build public confidence in approved
vaccines, as surveys show a majority of Americans areas and to new companies, to address issues that
would trust scientific research findings more if data are important for patients, such as drug pricing
were publicly shared. Given that there are no legal and equity and inclusion in research, to name a
obligations to publish or share patient-level trial data few. The next rankings include, for the first time,
with the public or health-care providers, we must rely companies of all sizes. The hope is that as ethical
on voluntary commitments by companies and other practices of pharma improve, as measured by this
research sponsors. The GPS can help us track, im- objective method, and progress is communicated to
prove and communicate progress on data sharing. the public, the industry will earn back the respect of
We believe we can continue to have a beneficial the people who depend on its products. People's lives
impact on the industry and patient care. We are depend on it. For more information, please visit
working to expand the scope of the GPS into new bioethicsinternational.org.
GM_10_9.indd 27 10/23/20 6:59 PM

bioethicsinternational.org
scientificamerican.com
GM_10_9.indd 28 10/23/20 6:59 PM

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GOOD

THE GOOD PHARMA

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4 Medicine for All 14 Opinion: SCIENTIFIC AMERICAN

2 GOOD MEDICINE: HEALTH, ETHICS & INNOVATION

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Project Editorial Director

SCIENTIFIC AMERICAN CUSTOM MEDIA 3

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4 GOOD MEDICINE: HEALTH, ETHICS & INNOVATION

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SCIENTIFIC AMERICAN CUSTOM MEDIA 5

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research agenda. 19 92 need some atten-

SCIENTIFIC AMERICAN CUSTOM MEDIA 7

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8 GOOD MEDICINE: HEALTH, ETHICS & INNOVATION

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BALANCING SPEED AND RIGOR

in “expanded access programs,”

SCIENTIFIC AMERICAN CUSTOM MEDIA 9

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10 GOOD MEDICINE: HEALTH, ETHICS & INNOVATION

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n 2018, a whistleblower employee of the Well-

SCIENTIFIC AMERICAN CUSTOM MEDIA 11

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12 GOOD MEDICINE: HEALTH, ETHICS & INNOVATION

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SCIENTIFIC AMERICAN CUSTOM MEDIA 13

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“Africans Need a Plan”

inequity gap. They make promises

14 GOOD MEDICINE: HEALTH, ETHICS & INNOVATION

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How Do Drugs Compare on Costs? In treating spinal muscular atrophy,

SCIENTIFIC AMERICAN CUSTOM MEDIA 17

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2013 2014 2015 2016 2017 2018 2019 2020

18 GOOD MEDICINE: HEALTH, ETHICS & INNOVATION

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SCIENTIFIC AMERICAN CUSTOM MEDIA 19

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ILLUSTRATIONS BY MARAVILLAS DELGADO

20 GOOD MEDICINE: HEALTH, ETHICS & INNOVATION

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SCIENTIFIC AMERICAN CUSTOM MEDIA 21

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22 GOOD MEDICINE: HEALTH, ETHICS & INNOVATION

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SCIENTIFIC AMERICAN CUSTOM MEDIA 23

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24 GOOD MEDICINE: HEALTH, ETHICS & INNOVATION

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# 5 Bristol-Myers Squibb 92%

SCIENTIFIC AMERICAN CUSTOM MEDIA 25

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# 1 Novo Nordisk 100%

Data Sharing to facilitate widespread data sharing among the in-

26 GOOD MEDICINE: HEALTH, ETHICS & INNOVATION

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