National epilepsy surgery program: realistic goals and pragmatic solutions.

There are multiple social, economic, and medical challenges in establishing successful epilepsy surgery programs in India and in other low- and middle-income countries (LAMIC). These can be overcome by reproducing pragmatic and proven epilepsy surgery models throughout the country with a larger aim of developing a national epilepsy surgery program so as to provide affordable and quality surgical care to all the deserving patients. An organized national epilepsy surgery support activity can help interested centers in India and in neighboring countries in developing epilepsy surgery programs.

Establishing an academic neurology specialty program: experiences over a five-year period.

Veterinary neurology is an expanding specialty field. At the time of this writing, 13 out of 33 (40%) US and Canadian veterinary colleges, and many more veterinary colleges outside of North America, had no active clinical neurology service. New academic programs will likely be established to fill this need, often starting with a single neurologist. Establishing a neurology service with one founding faculty member can be accomplished by developing the program in phases and creating a support network that optimizes faculty strengths and interests. Such an approach allows for the gradual expansion of services and staffing in a manageable way to ultimately provide a full-service program. A description of this development process at Purdue University School of Veterinary Medicine is presented as a case study and model for the establishment of other neurology or specialty services.

Medicine on the fringe: stem cell-based interventions in advance of evidence.

Stem cell-based interventions (SCBIs) offer great promise; however, there is currently little internationally accepted, scientific evidence supporting the clinical use of SCBIs. The consensus within the scientific community is that a number of hurdles still need to be cleared. Despite this, SCBIs are currently being offered to patients. This article provides a content analysis of materials obtained from SCBI providers. We find content that strains credulity and almost no evidence of SCBIs being delivered in the context of clinical trials. We conclude that until scientific evidence is available, as a general rule, providers should only offer SCBIs in the context of controlled clinical trials. Clients should be aware that the risks and benefits of SCBIs are unknown, that their participation is unlikely to advance scientific knowledge, and they are likely to become ineligible to participate in future clinical trials of SCBIs. We recommend steps to promote patient education and enhance global oversight.

Turning biodefense dollars into products.

Five years after the US anthrax attacks, and more than two years after BioShield legislation was ratified, a survey reveals that biodefense funding has thus far produced only a handful of products for clinical development.

Translational nanomedicine: status assessment and opportunities.

Nano-enabled technologies hold great promise for medicine and health. The rapid progress by the physical sciences/engineering communities in synthesizing nanostructures and characterizing their properties must be rapidly exploited in medicine and health toward reducing mortality rate, morbidity an illness imposes on a patient, disease prevalence, and general societal burden. A National Science Foundation-funded workshop, "Re-Engineering Basic and Clinical Research to Catalyze Translational Nanoscience," was held 16-19 March 2008 at the University of Southern California. Based on that workshop and literature review, this article briefly explores scientific, economic, and societal drivers for nanomedicine initiatives; examines the science, engineering, and medical research needs; succinctly reviews the US federal investment directly germane to medicine and health, with brief mention of the European Union (EU) effort; and presents recommendations to accelerate the translation of nano-enabled technologies from laboratory discovery into clinical practice. FROM THE CLINICAL EDITOR: An excellent review paper based on the NSF funded workshop "Re-Engineering Basic and Clinical Research to Catalyze Translational Nanoscience" (16-19 March 2008) and extensive literature search, this paper briefly explores the current state and future perspectives of nanomedicine.

Stimulating revolutionary science with mega-cash prizes.

We argue that the most ambitious science is intrinsically riskier science, more likely to fail. It is almost always a safer career strategy for the best scientists to seek to extend knowledge more modestly and to build incrementally on existing ideas and methods. Therefore, higher rewards for success are a necessary incentive to encourage top scientists to work on the most important scientific problems, ones where the solution has potentially revolutionary implications. We suggest that mega-cash prizes (measured in tens of millions of dollars) are a suitable reward for those individuals (or institutions) whose work has triggered radically new directions in science.

Molecular medicine: how, what, and when?

Integrating molecular medicine into clinical practice will create many challenges. But the existing genetic testing paradigm may not be the right model for introducing these new technologies.

Integrating molecular medicine into the US health-care system: opportunities, barriers, and policy challenges.

Scientific support about the concept of using molecular data for risk stratification and tailoring health-care interventions to the individual--a strategy broadly defined as molecular medicine (MM)--is accumulating. Molecular-based health-care technologies are beginning to enter clinical practice, but their use has revealed many scientific, economic, and organizational barriers to the effective delivery of targeted health care. We conducted a qualitative interview study to describe the MM landscape, with an emphasis on eliciting policy recommendations for the field from a broad range of stakeholders in MM and health care. Molecular medicine has widespread support but will require changes in how molecular-based technologies are evaluated, how health care is financed and delivered, and how clinicians and consumers are trained and prepared for its use. In particular, researchers and developers need to become active participants in a variety of clinical integration strategies to realize the promise of MM.

Will my malpractice case be settled? The physician-defendant's voice in the decision.

Malpractice claims are an unavoidable part of the practice of clinical medicine. Physicians purchase professional liability insurance to protect themselves from financial and other adverse consequences of such claims. Insurance policies require the insurer to hire attorneys to represent, defend and advise physicians who are named as defendants in medical malpractice lawsuits. Insurance policies require insurers to pay the costs associated with defending the lawsuit and paying, within policy limits, any damages for which a physician is determined to be liable. The relationship between insurer, defense counsel and physician can be complicated by divergent interests, concerns and priorities. It is important for physicians to be knowledgeable consumers when they are in the market for malpractice coverage. Familiarity with types of coverage, controls placed on defense costs and policy terms that determine decision-making authority on settlement issues are essential to making an informed purchase of insurance coverage.

Prizes to solve problems in and beyond medicine, big and small: it can work.

This article complements Dr. Charlton's follow-up of David Horrobin's suggestion in Nature two decades ago to offer sizeable prizes for practical approaches to either eliminate a problem in medicine or reduce the cost of its solution. Examples from the 20th and 21st centuries illustrate that prizes--small and big--have generated sustained and successful attacks on defined problems in biology, physics and, lately, mathematics. Provided that glittering prizes are offered and awarded with care, they can lead to effective problem-solving in medicine and related biomedical sciences as well.

Mega-prizes in medicine: big cash awards may stimulate useful and rapid therapeutic innovation.

Following Horrobin's suggestion of 1986, I argue that offering very large prizes (tens of millions of US dollars, or more) for solving specific therapeutic problems, would be an excellent strategy for promoting the rapid development of effective new treatments. The two mainstream ways of paying for medical research are funding the process with grants or funding the outcome via patent protection. When grants are used to fund the process of research the result tends to be 'pure' science, guided by intrinsic scientific objectives. Practical results, such as useful therapeutic advances, are a by-product. Patent-seeking research, by contrast, is more focused on technology than science. It seeks practical results; and aims to pay for itself (and make a profit) in the long term by generating a patentable product or procedure. Prize-seeking research is subject to different incentives and applicable to different situations than either process-funded or patent-seeking research. Prize seeking researchers have a strong incentive to solve the specified problem as rapidly as possible, but the problem may be solved using old ideas that are scientifically mundane or unpatentable technologies and methods. Prizes therefore seem to generate solutions which are incremental extensions, new applications or novel combinations of already-existing technologies. The main use of mega-prizes in medicine would be to accelerate therapeutic progress in stagnant fields of research and to address urgent problems. For example, medical charities focused on specific diseases should consider accumulating their resources until they can offer a mega-prize for solving a clinical problem of special concern to their patients. Prize money should be big enough to pay for the research and development, the evaluation of the new treatment in a clinical trial, and with a large profit left-over to compensate for the intrinsic risk of competing. Sufficiently large amounts of money, and the prestige and publicity derived from winning a mega-prize, could rapidly mobilize research efforts to discover a whole range of scientifically un-glamorous but clinically-useful therapeutic breakthroughs.

Biomedicine or holistic medicine for treating mentally ill patients? A philosophical and economical analysis.

Today we have two scientific medical traditions, two schools or treatment systems: holistic medicine and biomedicine. The two traditions are based on two very different philosophical positions: subjectivistic and objectivistic. The philosopher Buber taught us that you can say I-Thou or I-It, holding the other person as a subject or an object. These two fundamentally different attitudes seem to characterize the difference in world view and patient approach in the two schools, one coming from psychoanalysis and the old, holistic tradition of Hippocratic medicine. Holistic medicine during the last decade has developed its philosophical positions and is today an independent, medical system seemingly capable of curing mentally ill patients at the cost of a few thousand Euros with no side effects and with lasting value for the patient. The problem is that very few studies have tested the effect of holistic medicine on mentally ill patients. Another problem is that the effect of holistic medicine must be documented in a way that respects this school's philosophical integrity, allowing for subjective assessment of patient benefit and using the patient as his/her own control, as placebo control cannot be used in placebo-only treatment. As the existing data are strongly in favor of using holistic medicine, which seems to be safer, more efficient, and cheaper, it is recommended that clinical holistic medicine also be used as treatment for mental illness. More research and funding is needed to develop scientific holistic medicine.

Sound understanding of environmental, health and safety, clinical, and market aspects is imperative to clinical translation of nanomedicines.

Nanotechnology has transformed materials engineering. However, despite much excitement in the scientific community, translation of nanotechnology-based developments has suffered from significant translational gaps, particularly in the field of biomedicine. Of the many concepts investigated, very few have entered routine clinical application. Safety concerns and associated socioeconomic uncertainties, together with the lack of incentives for technology transfer, are undoubtedly imposing significant hurdles to effective clinical translation of potentially game-changing developments. Commercialisation aspects are only rarely considered in the early stages and in many cases, the market is not identified early on in the process, hence precluding market-oriented development. However, methodologies and in-depth understanding of mechanistic processes existing in the environmental, health and safety (EHS) community could be leveraged to accelerate translation. Here, we discuss the most important stepping stones for (nano)medicine development along with a number of suggestions to facilitate future translation.

Key challenges in bringing CRISPR-mediated somatic cell therapy into the clinic.

Genome editing using clustered regularly interspersed short palindromic repeats (CRISPR) and CRISPR-associated proteins offers the potential to facilitate safe and effective treatment of genetic diseases refractory to other types of intervention. Here, we identify some of the major challenges for clinicians, regulators, and human research ethics committees in the clinical translation of CRISPR-mediated somatic cell therapy.

A study of the status of clinical cancer research in the United States (1990).

This study has confirmed a continuing decrease in the quality and quantity of young physicians entering academic careers in clinical oncology research, defined as cancer research requiring a clinician-patient interaction. Two major contributing factors were identified: the training programs and the research environment. The primary problems for the trainees were the financial insecurity of embarking on an academic career and the poor academic status of their role models in clinical cancer research. The problems regarding the environment of academic oncology and oncology research relate primarily to the strong and widespread perception that grant proposals for clinical oncology research are at a competitive disadvantage with proposals for cancer research in the laboratory. The study results yielded two basic recommendations. The first recommendation is to improve training for clinical cancer research and to implement unique funding mechanisms for trainees. Because physicians devote 3-10 years to clinical training, a minimum of 10 years of clinical research is needed for a clinician to compete effectively as a principal investigator in the R01 and P01 grant areas. The second recommendation is to develop peer review mechanisms that allow clinical research proposals to compete within a pool restricted to proposals in this category. The consensus in the study was that when programs in clinical research and laboratory research are in competition, the clinical proposals have a lower success rate. The problem appears to rest with the fact that the reviewers are frequently from disciplines other than clinical research and, more importantly, that clinical research proposals fare badly in competition against laboratory research proposals even when they are reviewed by appropriate peers. Implementation of this recommendation will require development of a clinical oncology research study section in the Division of Research Grants at the National Institutes of Health to review R01 grant proposals for innovative clinical cancer research, providing an academic environment that would enable the clinical investigator, through increased success in obtaining grants, to be a positive role model for the young physician/scientist.

Obstacles facing translational research in academic medical centers.

Over the last quarter of the 20th century, there has been a boom in biomedical research discoveries that, for the most part, has not been successfully exploited for improving medical therapy or diagnosis. This lack of success is surprising because there is a broad consensus within academic medical centers (AMCs) that a primary mission is to move scientific discoveries into meaningful clinical outcomes, and there are numerous opportunities for doing so. We illustrate the latter point with 10 clinical opportunities for translating scientific discoveries from our field of vascular biology and transplantation. We attribute the limited success of translation to various factors, chief of which is that translation is rarely straightforward and requires continuing research in both the clinic and the laboratory. Translational research is hindered by insufficient targeted resources, a shortage of qualified investigators, an academic culture that hinders collaboration between clinical and laboratory-based investigators, a traditional structure of the AMC that favors departmental efforts over interdisciplinary programs, an increasing regulatory burden, and a lack of specific mechanisms within the AMC for facilitating solutions to these problems. We offer several suggestions to reduce these impediments.