Insulin-like growth factor binding protein (IGFBP6) is a cross-species tendon marker.

The main challenge in tendon injury management is suboptimal tissue healing that fails to re-establish original tendon function. Tissue bioengineering is a promising approach for tendon therapy, with potential to improve its functional outcomes. However, evaluation criteria for tissue-engineered tendon are unclear due to the lack of specific markers of differentiated tendon. The study aim was to identify a panel of genes that characterised tendons in comparison to cartilage or muscles and validate those genes, both in human and key species used as models for tendon diseases. Gene expression profiling of rat tendon and cartilage in whole-tissue samples and primary tenocytes and chondrocytes was undertaken using two independent microarray platforms. Genes that demonstrated high expression correlation across two assays were validated by qRT-PCR in rat tendon relative to cartilage and muscle. Five genes demonstrating the highest tendon-related expression in the validation experiment (ASPN, ECM1, IGFBP6, TNMD, THBS4) were further evaluated by qRT-PCR in ovine, equine and human tissue. The group of tendon markers, identified by unbiased transcriptomic analysis of rat musculoskeletal tissues, demonstrated species-dependent profiles of expression. Insulin-like growth factor binding protein 6 (IGFBP6) was identified as the only universal tendon marker. Further investigation in equine tendon showed that IGFBP6 expression was not affected by ageing or tendon function but decreased in anatomical regions subjected to elevated compressive force. IGFBP6 is a robust cross-species marker of tendon phenotype and may find application in evaluation of tendon physiology and guided differentiation of permissive cells towards functional tenocytes.

Regulatory Consequences of "Brexit" for the Development of Medicinal Products.

The United Kingdom voted in a referendum in June 2016 to leave the European Union (EU) after 45 years of membership. Among the many political, social, and scientific consequences are those for the regulation of health care products. No longer will the efficacy, safety, and quality of medicines in the United Kingdom be subject to an EU regulatory framework. The European Medicines Agency (EMA), which is currently located in London, will move elsewhere in Europe. The pharmaceutical industry will reassess its commitment to the UK health scene.

Regulatory review: How do agencies ensure the quality of decision making?

The Centre for Innovation in Regulatory Science (CIRS) Workshop on Regulatory Review brought together international regulators and multinational pharmaceutical company representatives to focus on best practices that underlie regulatory decision making, thereby facilitating the transparent, timely, procedurally predictable, and good-quality evaluation of new medicines. Participants investigated frameworks used by agencies, discussed challenges for regulatory agencies in making quality decisions, investigated the role of other stakeholders, and made recommendations of activities and processes that agencies and companies can consider to enable quality decision making.

Advancing the science of medicines regulation: the role of the 21st-century medicines regulator.

The history of medicines regulation is punctuated with sudden swings in focus mandated by a public injured by medicines and skeptical of regulators' abilities to protect them. As stakeholder communities and the science that undergirds medicines have both grown more sophisticated, seemingly conflicting mission equities, such as public health protection vs. promotion or population vs. individual patient product development focus, have created new challenges to defining the mission and role of twenty-first-century medicines regulators. The role of medicines regulators as a nationally focused, retrospective assessor of data is rapidly shifting to that of a prospective generator of public data and tools to help drive what has now become a global product development and regulatory enterprise that is fast gaining recognition as an integral part of any truly effective twenty-first-century health-care system. This article discusses this evolution and describes how regulatory science will help to both drive and define it.

The challenges of orphan drugs and orphan diseases: real and imagined.

The Orphan Drug Act of 1983 in the United States and similar legislation in Europe in 1999 provided incentives for companies to develop and sell medicines for diseases with a small market. In this Commentary, we outline the European position on the regulation of orphan drugs and explain where it differs from the regulation in the United States.

European perspective on risk management and drug safety.

Risk management is an approach that has been used for many years in areas of business and government such as finance and insurance, but its use in the regulation of medicines has until recently been limited to tools such as the prescription status of a medicine (prescription-only or over-the-counter), the information provided to health-care professionals and patients, and the collection and evaluation of postmarketing safety reports.

Medicines regulation and health technology assessment.

Health technology assessment (HTA) is as important as regulation to allow patients access to new medicines, and there are demands that the two processes should be carried out more closely together in time. Although the methods used by the regulator differ from those used by the health technology assessor, there is scope for synergies that would be useful to both parties. By providing scientific advice to sponsors of new medicines, both regulators and health technology assessors can also provide support for drug innovation.

Expediting patients' access to medicines by improving the predictability of drug development and the regulatory approval process.

Ideally, well-designed global pharmaceutical development programs that include simultaneous submissions to multiple regulatory agencies can result in predictable regulatory approvals and expedited access to medicines for all patients. The workshops described herein investigated current trends in development and submission strategies along with regulatory review performance data in order to consider whether barriers to predictable expedited approval outcomes can be overcome through innovative clinical development approaches and a better understanding of review processes and procedures, particularly as these relate to the assessment of a product's risk-benefit profile.

How European regulators view foreign data in the approval process.

The regulation of medicines should be based on sound scientific principles, and where these are uncertain the regulator may have difficulties. Nowhere is this illustrated more clearly than in the debate over how clinical data obtained in one part of the world can be used for regulatory purposes elsewhere.

Pharmacoeconomics comes of age?

Health services throughout the world face increasing demands on their limited resources, and decisions on the best use of these need to be informed by an examination of the costs and benefits of various options. Health economics provides a structure for this, whereas pharmacoeconomics adopts and applies the principles and methodologies of health economics to the field of pharmaceuticals and pharmaceutical policy.

The future of drug safety.

To provide a European perspective, I was invited to sit on the Institute of Medicine (IOM) committee that was charged with assessing the current system for evaluating and ensuring postmarketing drug safety in the United States. My colleagues on the committee came from a variety of professional backgrounds (health care, epidemiology, law, and economics), and the committee was managed by an experienced IOM staff member.

The burden of alcohol misuse on an inner-city general hospital.

Alcohol consumption in the UK has been increasing steadily. We prospectively studied the burden on hospital services caused by overt alcohol misuse, in an inner-city hospital in north-west England. All Accident & Emergency (A&E) patients were assessed to determine whether their hospital attendance was alcohol-related, and whether this resulted in admission and/or generated new out-patient appointments. Over 2 months, 1915 patients attended A&E with alcohol-related problems, accounting for 12% of attendances; 50% were aged 18-39 years, and acute alcohol intoxication was the commonest presenting complaint. Overall, 6.2% of all hospital admissions were due to alcohol-related problems. Over 2800 new out-patient visits were likely to have been generated over an 18-month period from initial attendance with an alcohol-related problem, mostly for orthopaedic clinics. The burden placed by overt alcohol-related problems on hospitals is enormous, both in terms of the emergency and out-patient services. The implementation of education, screening and intervention strategies in A&E departments, and employment of key trained personnel, should be considered, to optimize the clinical management of these patients.