[Show abstract][Hide abstract] ABSTRACT: This study aimed to systematically evaluate safety of probiotics and synbiotics in children ageing 0-18 years. This study is the third and final part in a safety trilogy and an update is provided using the most recent available clinical data (2008-2013) by means of the Common Terminology Clinical Adverse Events (CTCAE version 4.0) classification. Safety aspects are represented and related to number of participants per probiotic strain/culture, study duration, dosage, clinical condition and selected afflictions. Analysis of 74 clinical studies indicated that probiotic and/or synbiotic administration in children is safe with regard to the specific evaluated strains, dosages and duration. The population of children include healthy, immune compromised and obese subjects, as well as subjects with intestinal disorders, infections and inflammatory disorders. This study revealed no major safety concerns, as the adverse events (AEs) were unrelated, or not suspected to be related, to the probiotic or synbiotic product. In general the study products were well tolerated. Overall, AEs occurred more frequent in the control arm compared to children receiving probiotics and/or synbiotics. Furthermore, the results indicate inadequate reporting and classification of AEs in the majority of the studies. In addition, generalizability of conclusions are greatly limited by the inconsistent, imprecise and potentially incomplete reporting as well as the variation in probiotic strains, dosages, administration regimes, study populations and reported outcomes.
[Show abstract][Hide abstract] ABSTRACT: Our aim was to determine whether a fermented milk drink containing probiotics could improve the bowel habits of frail elderly individuals living in a nursing home. A total of 135 participants were enrolled in this pilot study. The bowel habits (stool quality and bowel movements) were recorded by nursing staff during a baseline period of 3 weeks. After this period participants received daily a fermented milk drink containing minimally 6.5×109 colony forming units of i>Lactobacillus casei Shirota (LcS) for 6 weeks. During this period, bowel habits were recorded and compared to baseline period. Forty-four participants (74'99 years old) were compliant and used for analysis. Consummation of fermented milk containing LcS significantly increased the percentage of ideal stool types per week (P<0.01), lowered the percentage of constipation stool types per week (P<0.01) and significantly lowered the percentage of diarrhoea stool types per week (P=0.016) as compared to the baseline period. The study product had no significant effect on bowel movements. During the study, no changes in laxative usage or adverse events associated with the study product were reported. Our results suggest that a fermented milk containing LcS significantly improves the bowel habits of frail elderly residents in a nursing home. These promising results should be further substantiated by a confirmatory study.
[Show abstract][Hide abstract] ABSTRACT: This study aimed to systematically evaluate safety of probiotics and synbiotics in immune compromised adults (≥18 years). Safety was analysed using the Common Terminology Clinical Adverse Events (CTCAE version 4.0) classification, thereby providing an update on previous reports using the most recent available clinical data (2008- 2013). Safety aspects are represented and related to number of participants per probiotic strain/culture, study duration, dosage, clinical condition and selected afflictions. Analysis of 57 clinical studies indicates that probiotic and/or synbiotic administration in immune compromised adults is safe with regard to the current evaluated probiotic strains, dosages and duration. Individuals were considered immune compromised if HIV-infected, critically ill, underwent surgery or had an organ- or an autoimmune disease. There were no major safety concerns in the study, as none of the serious adverse events (AE)s were related, or suspected to be related, to the probiotic or synbiotic product and the study products were well tolerated. Overall, AEs occurred less frequent in immune compromised subjects receiving probiotics and/or synbiotics compared to the control group. In addition, the results demonstrated a flaw in precise reporting and classification of AE in most studies. Furthermore, generalisability of conclusions are greatly limited by the inconsistent, imprecise and potentially incomplete reporting as well as the variation in probiotic strains, dosages, administration regimes, study populations and reported outcomes. We argue that standardised reporting on adverse events (CTCAE) in 'food' studies should be obligatory, thereby improving reliability of data and re-enforcing the safety profile of probiotics.
[Show abstract][Hide abstract] ABSTRACT: The management and exploitation of biotechnological product innovation have proven to be more difficult than initially expected because the number of currently marketed biotechnological products is far from sufficient to counter deficits in pharmaceutical innovation. This study provides insight into the role of governance structures in interfirm cooperation and their effects on biotechnological product innovation and company success. Most of the existing literature regarding alliances and mergers and acquisitions (M&A) examines their effects on technology recipients' innovation performance. Here, the effects of alliances and M&A on both the innovation success and financial performance of technology suppliers (i.e., sources) are examined. Drawing from a sample of 220 human therapeutic biotechnology and biopharmaceutical firms over a period of 32 years (1980–2011), an analysis of the effects of biotechnology clusters, strategic alliances, and acquisitions is provided. This study reveals the existence of a risk-return trade-off for strategic alliances between biotech companies and larger, more established firms. Increased biotech company involvement in product development alliances decreases risk by increasing the likelihood of future product introductions. The trade-off, however, is that biotech companies earn lower returns when their products are developed through such alliances. A similar risk-return trade-off effect is found for clusters. However, acquisitions generally affect both product introductions and product returns in a negative way. These findings have strategic implications not only for managing the development of biotechnological product innovations and technology platforms but also for commercialization strategies with respect to interfirm cooperation and risk reduction.
[Show abstract][Hide abstract] ABSTRACT: A plethora of terms and definitions for medical nutrition has resulted in an ambiguity in the way “medical nutrition” is termed and defined across various societal levels. The terms medical nutrition, clinical nutrition, enteral nutrition, parenteral nutrition, oral nutritional supplements, medical foods, foods for special medical purposes, nutritional support, nutritional intervention and nutritional therapy are used interchangeably. To date consistent terminology/nomenclature and definitions have not emerged from the US and European medical nutrition community. The current absence of clear medical nutrition product category boundaries makes it necessary to introduce medical nutrition terminology conformance in order to reduce widespread confusion at policy; industry; healthcare; and patient level. In order to end discussion, this literature review attempts to put quantitative and qualitative clarity and continuity to the use of these terms and definitions by: (1) addressing the terminology used; (2) discussing the distinguishing features of medical nutrition in various definitions and (3) proposing a single medical nutrition term and a clear pragmatic operational definition. A scientific literature-based comparison was conducted resulting in the selection of 22 publications, describing 8 different terms with 19 definitions.
Based on the terminology found in literature, the following medical nutrition terminology is proposed: medical nutrition comprises both parenteral (intravenous) as well as enteral nutrition (tube feeding and oral nutrition), which may be given via the oral route or via a tube into the gastrointestinal tract. The features found to be most important in describing medical nutrition are: route of administration; disease; supervision; composition and support/management. These features have been integrated into one operational clinical definition and resulted in the following definition: MEDICAL NUTRITION: specially formulated nutritional composition for the dietary management of patients with diseases, disorders or medical conditions that cause distinct nutritional requirements. It may consist of partial or exclusive feeding by means of oral intake, tube feeding and/or parenteral administration under healthcare professional supervision.
[Show abstract][Hide abstract] ABSTRACT: This exploratory qualitative article analyzes the potentially rate-limiting factors affecting value chain dynamics during adjuvanted-vaccine development. Adjuvants are considered immunostimulating substances that can be added to a vaccine. Although adjuvants have the potential to elicit adverse reactions, they also offer certain benefits. After approximately 90 years of R&D, why have only four adjuvants been approved? Although ample literature is available describing the risks and benefits, it remains unclear as to how these potentially rate-limiting factors compare.
Experts – representing knowledge institutes, industry and regulatory/public health authorities – were approached in order to collect a unique weighted-ranking dataset on rate limiting factors. Based on the principal–agent theory, there is a partial conflict of interests between the internal perceptions on the challenges faced. Additionally, content analysis reveals four underlying social constructs influencing this perception, namely: attitudes towards risk management, innovation strategy, valuation and funding.
This study was designed to explore the topic of rate-limiting factors, and not intended to solve the issues. Moreover we offer previously unpublished and practical insights on the topic, and offer a validated starting point for further research. Ultimately, we would advocate more transparency on reasons for project discontinuation; sharing lessons learned from failed attempts could prove valuable for advancing the field of virosciences.
Technological Forecasting and Social Change 05/2014; 90. DOI:10.1016/j.techfore.2014.04.017 · 1.71 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: In this study, we systematically evaluated safety aspects in clinical trials with probiotics and synbiotics in young infants (0-2 years of age). This study is an update of earlier reports and covers the recent literature from 2008-2013. The safety evaluation is performed along the Common Terminology Clinical Adverse Events (CTCAE) version 4.0 scale, hereby also providing guidance for future studies. Safety aspects are represented and related to number of participants per probiotic strain/culture, study duration, dosage, clinical condition and selected afflictions. The results show a deficiency in the precise reporting and classification of adverse events in most studies. Analysis of 57 clinical trials with probiotics and synbiotics in combination with eight follow-up studies indicate that probiotic administration to infants between 0 and 24 months is safe with regard to the evaluated strains in infants with a particular health status or susceptibility. Most adverse events and serious adverse events were considered unrelated to the study product, and there were no major safety concerns. Almost all studies concluded that none of the adverse effects were related to the study product; the study products are generally well tolerated. Finally, inconsistent, imprecise and potentially incomplete reporting as well as the variation in probiotic strains, dosages, administration regimes, study populations and reported outcomes, greatly limit the generalizability of conclusions and argue convincingly for obligatory and standardised behaviour on adverse events (CTCAE) reporting in 'food' studies.
[Show abstract][Hide abstract] ABSTRACT: At present, industries within the health and life science sector are moving towards one another resulting in new industries such as the medical nutrition industry. Medical nutrition products are specific nutritional compositions for intervention in disease progression and symptom alleviation. Industry convergence, described as the blurring of boundaries between industries, plays a crucial role in the shaping of new markets and industries. Assuming that the medical nutrition industry has emerged from the convergence between the food and pharma industries, it is crucial to research how and which distinct industry domains have contributed to establish this relatively new industry. The first two stages of industry convergence (knowledge diffusion and consolidation) are measured by means of patent analysis. First, the extent of knowledge diffusion within the medical nutrition industry is graphed in a patent citation interrelations network. Subsequently the consolidation based on technological convergence is determined by means of patent co-classification. Furthermore, the medical nutrition core domain and technology interrelations are measured by means of a cross impact analysis. This study proves that the medical nutrition industry is a result of food and pharma convergence. It is therefore crucial for medical nutrition companies to effectively monitor technological developments within as well as across industry boundaries. This study further reveals that although the medical nutrition industry's core technology domain is food, technological development is mainly driven by pharmaceutical/pharmacological technologies Additionally, the results indicate that the industry has surpassed the knowledge diffusion stage of convergence, and is currently in the consolidation phase of industry convergence. Nevertheless, while the medical nutrition can be classified as an industry in an advanced phase of convergence, one cannot predict that the pharma and food industry segments will completely converge or whether the medical industry will become an individual successful industry.
PLoS ONE 12/2013; 8(12):e82609. DOI:10.1371/journal.pone.0082609 · 3.23 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: A quantitative systematic identification and prioritization of unmet needs and research opportunities in relation to enteral nutrition was conducted by means of a tailor-made health research prioritization process.
The research objectives were reached by conducting qualitative interviews followed by quantitative questionnaires targeting enteral nutrition key opinion leaders (KOLs). (1) Define disease areas that deserve more research attention; (2) Rank importance of product characteristics of tube feeding (TF) and oral nutritional supplements (ONS); (3) Assess involvement of KOLs in enteral nutrition R&D process. KOLs ranked three product characteristics and three disease areas that deserve additional research attention. From these, overall priority scores were calculated by multiplying ranks for both product characteristics and disease areas.
17 qualitative interviews were conducted and 77 questionnaires (response rate 35%) were completed and returned. (1) Disease areas in ONS and TF with highest priorities are: ONS: general malnutrition & geriatrics, TF: intensive care. (2) TF product characteristics with highest priorities are: composition and clinical evidence from a KOL perspective; tolerance and ease of use from a patient perspective. ONS product characteristics with highest priorities are: composition, clinical evidence and taste from a KOL perspective; taste from a patient perspective. We find a high discrepancy between product characteristic prioritization from a KOL and patient perspective. (3) Although 62% of all KOLs give advice to enteral nutrition companies on patient needs, they under-influence the setting of research priorities by enteral nutrition companies.
This study provides a systematic approach to achieve research prioritization in enteral nutrition. In addition to providing new directions for enteral nutrition research and development, this study highlights the relevance of involving KOLs in the identification of research priorities as they have the ability to provide a balanced view of the unmet patient needs.
[Show abstract][Hide abstract] ABSTRACT: Recent studies suggested that manipulation of the composition of the microbial ecosystem in the gut might be a novel approach in the treatment of obesity. Such treatment might consist of altering the composition of the microbial communities of an obese individual by administration of beneficial microorganisms, commonly known as probiotics. Here, we intend to contribute to the developmental process of probiotic treatment of human obesity. The aim is to review the evidence regarding the potential effect of probiotic strains on reduction of weight and body fat. A literature study was conducted focusing on clinical trials that examined the effect of specific microorganisms on body weight control. Analysis of the eligible articles pointed out that Lactobacillus gasseri SBT 2055, Lactobacillus rhamnosus ATCC 53103, and the combination of L. rhamnosus ATCC 53102 and Bifidobacterium lactis Bb12 may reduce adiposity, body weight, and weight gain. This suggests that these microbial strains can be applied in the treatment of obesity. Furthermore, short chain fatty acid production and low grade inflammation were found as the underlying mechanisms of action that influence metabolism and affect body weight. These findings might contribute to the development of probiotic treatment of obesity. Further research should be directed to the most effective combination and dosage rate of probiotic microorganisms.
[Show abstract][Hide abstract] ABSTRACT: During the past two decades the biopharmaceutical industry has been facing an innovation deficit, characterized by in- creasing research & development costs and stagnant productivity. From its inception, biotechnology has been expected to counter this deficit by its revolutionary science-based approach to drug discovery. For this study we gathered patent and product data related to the technological development of the first two biotechnologies: recombinant DNA technol- ogy and monoclonal antibody technology. We studied the technological lifecycles of these technologies in terms of sci- entific discoveries and inventions as well as product innovations. Results indicate that over the years inventions related to these technologies have simultaneously become less radical and less valuable. Furthermore, our analysis shows that these biotechnologies have reached a stage of technological limit or saturation, which may be followed by an innovation cliff. Now, more than ever, it is crucial to examine new strategies and opportunities for value creation, capturing, and delivery, within the biopharmaceutical industry.
Technology and Investment 07/2013; 43020(4):168-178. DOI:10.4236/ti.2013.43020
[Show abstract][Hide abstract] ABSTRACT: Innovation is a necessity for survival in dynamic and complex industries such as the medical nutrition industry. To remain competitive, medical nutrition companies must embrace innovation activities that improve productivity. Nevertheless, innovation is a difficult undertaking and companies must first overcome numerous barriers inhibiting innovation. Studying these barriers provides insight into the dynamics of innovation, which simultaneously is a first step in the process of overcoming them. This study investigates the exogenous barriers that inhibit medical nutrition innovation.Primary data was collected by qualitative interviews from 17 medical nutrition key opinion leaders (KOLs) through and quantitative data by means of a questionnaire from 77 KOLs. Medical nutrition innovation barriers were identified and ranked according to importance.This study shows that barriers impact all steps of the medical nutrition value chain. Nine main innovation barriers emerged from the research. The most significant barriers are associated with financial aspects and clinical research, whereas the least significant are associated with product barriers. Medical nutrition companies must realize that investment in innovation is and remains crucial within this industry.
[Show abstract][Hide abstract] ABSTRACT: In the medical nutrition (MN) market, insights into the motives driving intellectual property (IP) protection strategies remain unclear. This emerging market has expressed the pressing need for clarity on the subject of applicable IP methods. The aim of this study is therefore to evaluate the role of patents and alternative IP instruments for the protection of innovations in the MN market, and to construct an IP decision framework facilitating IP selection. Data collection consists of a literature study on the topic of IP strategies, combined with a supplementary questionnaire sent out to MN companies.Although there are many different strategic motives to apply for a patent in the MN market, the classic protective motives prove to be most important. While our findings acknowledge that patenting is of paramount importance to this industry, different scenarios call for combining the various IP methods for the optimal protection of the MN innovation. One must therefore always carefully consider additional IP rights. Our IP decision framework provides both MN companies and academic R&D departments with a tool to assess the best applicable IP strategy for the protection of MN inventions.
[Show abstract][Hide abstract] ABSTRACT: In the past two years an enormous amount of molecular, genetic, metabolomic and mechanistic data on the host-bacterium interaction, a healthy gut microbiota and a possible role for probiotics in Clostridium difficile infection (CDI) has been accumulated. Also, new hypervirulent strains of C. difficile have emerged. Yet, clinical trials in CDI have been less promising than in antibiotic associated diarrhoea in general, with more meta-analysis than primary papers on CDI-clinical-trials. The fact that C. difficile is a spore former, producing at least three different toxins has not yet been incorporated in the rational design of probiotics for (recurrent) CDI. Here we postulate that the plethora of effects of C. difficile and the vast amount of data on the role of commensal gut residents and probiotics point towards a multistrain mixture of probiotics to reduce CDI, but also to limit (nosocomial) transmission and/or endogenous reinfection. On the basis of a retrospective chart review of a series of ten CDI patients where recurrence was expected, all patients on adjunctive probiotic therapy with multistrain cocktail (Ecologic®AAD/OMNiBiOTiC® 10) showed complete clinical resolution. This result, and recent success in faecal transplants in CDI treatment, are supportive for the rational design of multistrain probiotics for CDI.
[Show abstract][Hide abstract] ABSTRACT: Medical nutrition products are specific nutritional compositions for intervention in disease progression and symptom alleviation. This industry finds itself on the interface between the food and pharmaceutical industry and is still a relatively unknown industry. At present, insights concerning industry development and patenting in the European medical nutrition industry are limited. This research presents a systematic patent portfolio analysis of the industrial patenting trends and patenting strategy categorization of the 5 leading companies.Focusing on EU patent applications, we calculated company specific patent-, product- and market shares and average forward- and backward-citations. These indicators were combined to illustrate the European medical nutrition industry trends and company specific patent- and innovation-strategies. We found 222 European medical nutrition patent applications between 1990 and 2010.The analysis of the industry trends shows that the industry currently resides in the growth phase and is estimated to reach the stage of maturation within 2 years with approximately 400 patents. Predominantly neurological diseases, cancer and diabetes show opportunity for future MN innovations while gastrointestinal and infection related diseases may have already reached a market saturation stage. Three distinct patent strategies can be distinguished within this industry: the Prospector; the Analyzer; and the Reactor.
[Show abstract][Hide abstract] ABSTRACT: As infectious diseases cause approximately 25% of the annual global mortality, vaccines are found to be a time proven and promising response to infectious disease need. However, like for pharmaceutical small molecules, vaccine development is lengthy, risky and resource demanding. Faced with an attrition rate estimated around 80%, key opinion leaders were interviewed with the question: is there a recipe for success?