COMMENT

Beyond magic bullets: true innovation

in health care
Vaibhav A.Narayan, Marco Mohwinckel, Gary Pisano, Michael Yang and
Husseini K.Manji

The time has come to move beyond product-focused magic bullet therapeutic development
strategies towards models that can also incorporate devices, tools and services to provide
integrated health-care solutions.

Vaibhav A.Narayan and

Husseini K.Manji are
at Janssen Research &
Development, LLC, Raritan,
New Jersey 08869, USA.
Marco Mohwinckel is at
Janssen Healthcare
Innovation, London HP12
4EG, UK.
Gary Pisano is at Harvard
Business School, Boston,
Massachusetts 02138, USA.
Michael Yang is at Janssen
Pharmaceuticals, Inc.,
Titusville, New Jersey
08560, USA.
Correspondence to H.K.M.
e-mail: hmanji@its.jnj.com
doi:10.1038/nrd3944

The molecular medicine revolution based on advances

in fields such as genomics and network modelling in the
decade since the human genome sequence was com
pleted has changed the way we think about, study and
approach the development of novel therapies. However,
these advances in knowledge have so far not been
reflected in substantial medical progress in many areas.
Organizations involved in pharmaceutical research and
development (R&D) now often find themselves caught
between twin pincers of disease biology complexity and
a continually rising bar for differentiation from existing
therapies.
This crisis is perhaps most apparent in the develop
ment of drugs for central nervous system (CNS) dis
orders. Neurodegenerative diseases have been identified
as the biggest challenge not only for health care but also
for overall economics worldwide. Moreover, mental
illnesses have been identified as the leading cause of
disability; their predicted cost to society worldwide is
higher than that of cancer, diabetes and chronic res
piratory diseases combined 1. In the context of this
huge unmet need, it is noteworthy that although many
believe that we are in the golden age of neuroscience,
the scientific breakthroughs have not yet resulted in
commensurate transformational therapeutic advances.
Part of the reason for this lack of progress is likely to
have been too great a focus on developing single magic
bullet drugs for very complex diseases. Although seri
ous mental illnesses are among the most heritable of
diseases, indicating a strong biological basis, they arise
out of the inheritance of multiple susceptibility and pro
tective genes that interact stochastically and with envi
ronmental factors to produce phenotypes that manifest
as a constellation of symptoms, including changes in
cognition, mood, perception and dysregulation of auto
nomic, endocrine and circadian pathways. It is therefore
unlikely that single-target drugs will adequately treat all
facets of such complex diseases.

Consequently, there is a growing appreciation of the

need to harness advances in understanding of network
dynamics to identify critical nodes whose concurrent
targeting may result in optimal intervention in patho
physiological states2. Furthermore, our notion of combina
tion therapy should not be constrained to combinations
of pharmacological agents. For example, given that severe
neuropsychiatric disorders may arise from regional
abnormalities in synapse and circuit dynamics, such
regional dynamics might best be targeted with a com
bination of pharmacological and non-pharmacological
interventions, including devices. Indeed, progress has
already been made in the development of electric, mag
netic, robotic and digital (software-based) approaches for
treating various CNS disorders. These range from devices
for neurostimulation, such as deep brain stimulation for
Parkinsons disease and vagus nerve stimulation for epi
lepsy, to software-based interventions to improve the
cognitive deficits associated with schizophrenia. The con
current use of the targeted drugs and devices to engage
specific neuronal circuits may be the best approach to
facilitate use-dependent plasticity without targeting neu
ronal circuits unaffected by disease pathology.
In our view, to succeed in the evolving health-care
environment, R&D organizations will need to broaden
their definition of innovation even further and move
towards developing novel integrated solutions that go
beyond molecular innovation. As power shifts towards
payers and patients/caregivers, definitions of innovation
particularly in the context of complex diseases will
broaden to include outcomes that are meaningful and
measurable to them. For example, in major depression,
value may be defined by the ability to rapidly resume social
and work responsibilities; for pain, it may be defined as
the ability to quickly resume physical activities of choice;
and for Alzheimers disease, it may be defined in terms
of benefits that allow patients to remain independent for
longer. Developing tools and technology that not only

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COMMENT
demonstrate such benefits at the population level but
also communicate them to individual patients and/or
their care-givers will be an important challenge.
Therefore, in such an environment, the main driver
of improved outcomes and meaningful benefits may
not be innovative therapeutics alone but an ecosystem
comprising the therapeutic and wrap-around tools and
services. For example, integrated solutions that improve
adherence and access to an existing drug could have as
much impact on health outcomes as introducing new
drugs. This is particularly true for many serious men
tal illnesses that can directly affect individuals insight
into their disease and often their ability to adhere to
medications3. Schizophrenia provides an important
example. Lack of adherence to prescribed medications
can put patients at risk of serious symptomatic episodes,
but even patients with schizophrenia who are other
wise motivated to adhere to their medications may be
impeded by lack of access to medicines in a fragmented
health-care system that disrupts coordination and con
tinuity of care. Addressing some of these challenges by
simplifying care pathways and ensuring benefits beyond
clinical outcomes could be a cornerstone of innovation
for health-care companies.
Furthermore, to successfully implement compre
hensive therapeutic intervention, the ability to inter
cept disease is crucial. This involves a paradigm shift
from a diagnose and treat approach to a predict and
pre-empt model. Obviously, the most direct avenue for
intercepting disease is prevention, but pre-emption
that is, intervening early enough in the disease process
to prevent serious effects of the disease associated with
progression will also be important. This is particu
larly true for diseases such as cancer or Alzheimers dis
ease, for which the efficacy of a given treatment could
be vastly enhanced by earlier intervention. Indeed, an
early diagnosis paradigm should be an integral part of
any therapeutic strategy. It should be noted, however,
that the trajectory of many diseases is cyclical, thus offer
ing multiple interception opportunities to prevent seri
ous decline for example, predicting and pre-empting
relapse in schizophrenia, mania in bipolar disorder,
recurrence/suicidality in severe depression, or stroke
or myocardial infarction in patients with cardiovascu
lar disease. Measuring physiological and activity-based
parameters remotely and continuously via unobtrusive
on-body sensors or smartphones has the potential to rev
olutionize our ability to predict and pre-empt harmful
changes in disease trajectory 4. Cheaper and more widely
distributed diagnostics, remote monitoring, pervasive
mobile computing and non-pharmacological interven
tions such as computerized cognitive therapies also have
the potential to overcome traditional barriers of access
and adherence to disease interception modalities.
Taken together, these changes indicate a future char
acterized by integrated health-care models that take the
concept of intervention beyond the pill to more com
prehensive approaches that include monitoring, helping
with adherence and disease interception. Furthermore,
these models could provide a mechanism for society to

assess the full costs and benefits of intervention strate

gies and will allow health-care companies to pilot new
integrated solutions in both controlled environments
and in the real world. For example, significant reduc
tions in relapse-related hospitalization rates have been
demonstrated for patients in Germany suffering from
schizophrenia and bipolar disorder who have been
enrolled into integrated care models that improve
the overall quality of care and medication adherence
through a more structured and holistic communitybased programme, in which care in hospital and com
munity settings is effectively coordinated (see Further
information). The US National Institute of Mental
Health has also launched the Recovery After an Initial
Schizophrenia Episode (RAISE) initiative, which
attempts to bring together services of different types that
may improve outcome. Another example is provided by
the Cleveland Clinic, which has created 18 institutes
that use multidisciplinary teams to treat diseases or
problems involving a particular organ system instead of
having patients bounce from one specialist to another
on theirown.
Numerous scientific, regulatory and commercial
challenges remain in implementing and capturing value
from such beyond the pill integrative solutions. New
regulatory paths need to be delineated to evaluate and
approve multi-modal therapeutics, payer and policy
hurdles will need to be overcome and traditional busi
ness models within health care will have to evolve to
encompass the ecosystems of drugs, devices, diagnos
tics and services. However, these challenges, although
daunting, are not insurmountable. As we continue to
make major, much-needed advances at the level of dis
ease biology, we must also innovate on multiple fronts
in the health-care system to bring about truly improved
outcomes for patients with some of societys most devas
tating diseases.
1.
2.
3.
4.

World Economic Forum. The Global Economic Burden of

Non-communicable Diseases (Harvard School of Public
Health, 2011).
Schadt, E. E. & Bjrkegren, J. L. NEW: network-enabled wisdom
in biology, medicine, and health care. Sci. Transl. Med. 4, 115rv1
(2012).
Kane, J. M. Improving treatment adherence in patients with
schizophrenia. J.Clin. Psychiatry 72, e28 (2011).
Madan, A., Cebrian, M., Lazer, D. & Pentland, A. Social sensing
for epidemiological behavior change. Proc.12th ACM Int. Conf.
Ubiquitous Computing 291300 (ACM, 2010).

Acknowledgements

W. P. Battisti (Janssen Research & Development, USA) provided administrative and editorial support for this manuscript.

Disclosure

All authors meet International Council of Medical Journal Editors criteria.

All authors have contributed to the development of this article and have
approved the submission.

Competing financial interests

The authors declare competing financial interests: see Web version for details.

FURTHER INFORMATION
Better managed care for schizophrenia patients in Germany:
http://cges.umn.edu/docs/vanLente_InnovativePartnerships.pdf
Recovery After an Initial Schizophrenia Episode (RAISE) initiative:
http://www.nimh.nih.gov/health/topics/schizophrenia/raise/index.shtml
ALL LINKS ARE ACTIVE IN THE ONLINE PDF

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