Research paradigms and useful inventions in medicine : patents and licensing by teams of clinical and basic scientists in Academic Medical Centers

In recent decades, teams that combine basic scientists with clinical researchers have become an important organizational mechanism to translate knowledge made in basic science (“the bench”) to tangible medical innovations (“the bedside”). Our study explores whether inventing teams that span basic and clinical research are more effective at licensing than teams comprised of inventors from only one domain. We propose that laboratory science and clinical research represent fundamentally different research paradigms that defy a simple arithmetic of combining the skills of individuals on teams. Clinical and basic researchers inhabit distinct cultures of work that yield different, and sometimes conflicting, beliefs and approaches to problem-solving. We claim that the complexity and variability of most human medical problems limits the role of basic science in medical innovation. Instead, we argue that clinical research remains an important engine of innovation, even in a period of rapid advances in molecular and genetics sciences, and advanced analytical techniques, because clinical researchers have unique opportunities for insights that emerge from the joint activities of research and close observations of living patients. Our empirical analysis focuses on patents and licenses from two prominent Academic Medical Centers (AMCs) over a 30 year period. In hazard models of licensing we find, controlling for a range of effects, that inventions by teams composed of clinical researchers (MDs) are more likely to be licensed than inventions by teams of basic scientists (PhDs), and that inventions that include both MDs and PhDs are not more likely to be licensed. This leads us to question the translational model of combining expertise to bridge different domains. We also find that the training of the team leader has an effect on licensing that is independent of team composition, lending support to our interpretation. Our results help inform policy about the relationship between research paradigms, team composition, and successful innovation in bio-medicine

Measuring exaptation and its impact on innovation, search, and problem solving

Exaptation, the emergence of latent functionality in existing artifacts, is an underexplored mechanism of novelty generation in innovation. In this paper, we measure the frequency of exaptation in the pharmaceutical industry. We find that about 42% of new functions derived from existing drugs have an exaptive nature. We think that this constitutes the first measure of exaptation in any industry. We also link exaptation with radical innovation and find that most radical innovations in our sample are exaptive. Also, nearly all radical innovations occur in market areas very distant from the drug’s original market. We propose that exaptive innovation constitutes a different search mechanism and problem-solving approach from deliberate innovation and discuss the role of context and serendipity in innovation

From Idea to Product - Translating Knowledge between the Lab and the Clinic

This dissertation is composed of three essays looking at innovation at Academic Medical Centers. It tries to empirically explore the problem of translating knowledge from the laboratory bench to the clinic and from the clinic to the bench. Chapter 1, co-authored with Iain Cockburn, establishes the importance of inhouse complementary knowledge in firm decision to license an invention from an Academic Medical Center. By using patent data to describe the technology portfolio of firms who look at patents and then decide whether to license them or not we are able to provide a description of demand in Markets for Technology. We show that firms license inventions that are similar to own technology portfolio when such similarity is measured at a broad level using International Patent Classes. However, controlling for such broad level proximity, firms are less likely to license inventions that are similar when measured at a more granular level. Chapter 2 asks: “Are inventions by teams from Academic Medical Centers that combine cross-domain knowledge at a higher hazard of licensing than inventions by single domain teams?” Inventors’ educational background is used to assign them to the clinical (MDs) or the research domain (PhD). Contrary to our expectations, we find that inventions by cross-domain teams are at a lower hazard of licensing. Similarly, inventions by cross-domain integrated teams (at least one MD/PhD) are at a lower hazard of licensing than inventions by cross-domain distributed teams (MD and PhD on team but no MD/PhD). However, medical device inventions tend to be at a higher hazard of licensing if invented by cross-domain teams. Chapter 3, co-authored with Rob Huckman, looks at how the routine clinical work of cardiac surgeons at Academic Medical Centers can impact their innovative performance as measured by quantity and quality of academic articles that they publish. We use the procedures that these cardiac surgeons perform every year to create a measure of clinical focus to understand whether diversity of work impacts innovation. Using a panel data with surgeon fixed effects we find that early career surgeons benefit from work diversity but late-career surgeons do not

The Major Role of Clinicians in the Discovery of Off-Label Drug Therapies

Objective: To determine, through a review of the medical literature and author contact, the role of clinicians in the discovery of off label use of Food and Drug Administration approved prescription drugs. Data Sources: The literature was accessed through MEDLINE (1999-December 2003). Additional sources accessed included the U.S. Patent Office and Micromedex, Thompson Scientific and Healthcare, Inc. Data Synthesis: A survey of new therapeutic uses for New Molecular Entity drugs approved in 1998 was conducted for the subsequent 5 years of commercial availability. During that time period, a total of 144 new applications were identified in a computerized search of the literature for the 29 new drugs approved in 1998. Literature and patent searches were conducted to identify the first report of each new application. Authors of the seminal articles were contacted via survey and telephone interview to determine whether they were in fact the originators of the new applications. If they were, examinations of article contents and author surveys were used to explore whether each new application was discovered via clinical practice that was independent of pharmaceutical company or university research (field discovery) or whether the discovery was made by or with the involvement of pharmaceutical firm or university researchers (central discovery). Conclusions: Post-NDA discoveries of new, off-label uses for new drugs were present in 22 of the 29 drugs in our sample. We found that 59% (85/144) of the drug therapy innovations in our sample were discovered by practicing clinicians via field discovery. The major role of clinicians in the discovery of new, off-label drug therapies has not been previously documented or explored. We propose that this finding has important regulatory and health policy implications

Detection of CMV DNA in intraocular fluid samples in patients clinically diagnosed with viral uveitis by molecular methods

Background: Latent Cytomegalovirus (CMV) infections may be reactive in consequence of immunosuppression. Recently, CMV-associated uveitis cases have also been reported in immunocompetent individuals. Aim: The aim of this study was to obtain epidemiological data by evaluating CMV DNA PCR results, clinical characteristics and risk factors of patients diagnosed with viral uveitis. Methods: Between the years 2011-2017, anterior chamber fluid samples of 35 patients with viral uveitis sent from the ophthalmology clinic to the Virology Laboratory were included in this study. CMV DNA real-time PCR results were evaluated. Results: CMV DNA positivity was detected in 9 (26%) of the 35 patients. CMV DNA positivity was highest (13%) in over 60 years (p=0.02). Acute recurrent uveitis in 44% (4/9) of patients, single eye involvement in 78% (7/9) and anterior uveitis in 44% (4/9) were found. Conclusion: In this study, CMV DNA positivity was detected in 26% of the patients with viral uveitis. Considering the presentations of a small number of cases related to CMV uveitis in our country, this study is important due to being the most comprehensive study in our country

Polymorphisms in the tumor necrosis factor-alpha gene in Turkish women with pre-eclampsia and eclampsia

The genetic background predisposing pregnant women to pre-eclampsia/eclampsia (PE/E) is still unknown. The aim of the current study was to investigate whether there is an association between the TNF-alpha-308 and 850 polymorphisms and PE or eclampsia. In this study, 40 cases of eclampsia, 113 cases of PE and 80 normotensive control cases were genotyped for the TNF-alpha-G-308A and C-850 polymorphisms. At position 308, the replacement of Guanine with Adenosine was denoted as TNF2. We found a significant difference between the TNF2 allele frequencies of the eclamptic, pre-eclamptic and normotensive controls. TNF2 (AA) polymorphism frequency was significantly higher among the eclamptics and pre-eclamptics (control : 5%, PE : 13.3%, E : 12.9%). A significantly different genotype distribution of C-850T polymorphism was observed between the PE/E and control groups, with the frequency of the variant TT genotype being significantly reduced in the preeclamptics (PE : 17% ; E : 17.5%) when compared with the control group (24.3%). We have demonstrated an association between TNF-alpha polymorphisms and pre-eclampsia susceptibility. However, it is not known whether C-850T polymorphism has a functional effect on the TNF-alpha gene. In addition, it was not possible to determine whether this polymorphism promotes the progression from PE to eclampsia because of no statistically significant difference between eclampsia and the controls

A 12-Year-Old Girl with Bilateral Coats Disease and ABCA4 Gene Mutation

A 12-year-old girl with bilateral stage 2B Coats disease was screened meticulously for a possible underlying systemic disease as she was female and the disease was bilateral. Full systemic workout turned out to be unremarkable. However, an ABCA4 gene mutation was found in the genetic analysis. NDP and TINF2 gene mutations were not present. She was successfully treated with a bilateral, single intravitreal injection of dexamethasone implant and a single session of indirect laser photocoagulation with a relatively good anatomic and functional result. To the best of our knowledge, the present case is the only reported case of Coats disease with an ABCA4 gene mutation

Serum neudesin levels in patients with polycystic ovary syndrome

Objectives: We aimed to investigate serum neudesin levels that has neural, metabolic functions in patients with polycystic ovary syndrome (PCOS). Material and methods: The study included 180 women (age range, 18–44 years) with a diagnosis of PCOS and a control group that included 100 healthy females (age range, 18–46 years). Body mass index (BMI), waist circumference, Ferriman-Gallwey score, was evaluated and plasma glucose, lipid profile, estradiol, progesterone, total testosterone, prolactin, insulin, dehydroepiandrosterone sulfate (DHEA-S), FSH, LH, free T3, free T4, thyroid stymulating hormone (TSH), anti-thyroperoxidase (anti-TPO) antibody and neudesin levels were evaluated in all participants. Results: BMI and waist circumference were similar between two groups. Ferriman-Gallwey score was significantly higher in the patient group. Fasting blood glucose, HbA1C, lipid parameters except triglyceride levels, free T3, free T4, TSH, anti-TPO were similar between the two groups. Triglyceride, insulin and HOMA values were significantly higher in PCOS patients. While follicle-stimulating hormone (FSH), estradiol, progesterone, prolactin and DHEAS levels were similar, LH was significantly higher in patients with PCOS. Serum neudesin level was significantly lower in PCOS patients with respect to controls (p = 0.015). Neudesin was positively correlated with insulin (r = 0.224, p = 0.037), and progesterone (r = 0.716, p = 0.001). Multiple regression analysis revealed that neudesin correlated with only progesterone (beta = 0.308, p = 0.001). Conclusions: Due to the association of decreased levels of neudesin with PCOS and correlation of neudesin with progesterone, neudesin may be related with one of patophysiologic pathways of PCOS. Still, it is not certain that decreased neudesin is involved in the pathogenesis of PCOS or is the result of the disorder

Global survey of the roles, satisfaction, and barriers of home healthcare nurses on the provision of palliative care

Background: the World Health Assembly urges members to build palliative care (PC) capacity as an ethical imperative. Nurses provide PC services in a variety of settings, including the home and may be the only health care professional able to access some disparate populations. Identifying current nursing services, resources, and satisfaction and barriers to nursing practice are essential to build global PC capacity. Objective: to globally examine home health care nurses' practice, satisfaction, and barriers, regarding existing palliative home care provision. Design: needs assessment survey. Setting/Subjects: five hundred thirty-two home health care nurses in 29 countries. Measurements: a needs assessment, developed through literature review and cognitive interviewing. Results: nurses from developing countries performed more duties compared with those from high-income countries, suggesting a lack of resources in developing countries. Significant barriers to providing home care exist: personnel shortages, lack of funding and policies, poor access to end-of-life or hospice services, and decreased community awareness of services provided. Respondents identified lack of time, funding, and coverages as primary educational barriers. In-person local meetings and online courses were suggested as strategies to promote learning. Conclusions: it is imperative that home health care nurses have adequate resources to build PC capacity globally, which is so desperately needed. Nurses must be up to date on current evidence and practice within an evidence-based PC framework. Health care policy to increase necessary resources and the development of a multifaceted intervention to facilitate education about PC is indicated to build global capacity