Search

Technological and scientific innovations in the area of gene and cell therapies, so-called advanced therapy medicinal products (ATMPs), have contributed to the steep increase in treatment options for patients with rare diseases. They offer opportunities to address the underlying genetic defect by gene addition, i.e., the delivery of the gene of interest to the target cells, or by genome editing approaches through direct repair of disease-causing mutations. This paper outlines clinical evidence requirements in the context of marketing authorisations for rare diseases. Two out of fifteen gene therapies that have been approved in the European Union since 2018 are used as case studies: Libmeldy (atidarsagen autotemcel) for the treatment of patients with metachromatic leukodystrophy, and Roctavian (valoctocogen roxaparvovec) for the treatment of patients with haemophilia A. Special aspects of the evaluation of single-arm trials with small sample size and requirements with regard to the isolation and causal attribution of the treatment effect are discussed. The role of clinical data obtained under everyday conditions (real world data) to support the generation of evidence in the pre- and post authorisation phase is critically examined. Furthermore, the paper outlines aspects related to conditional versus standard marketing authorisations as well as aspects related to registry-based non-interventional studies in the context of market and patient access to urgently needed drugs., (Copyright © 2024. Published by Elsevier GmbH.)

Somatic gene editing (SGE) holds great promise for making genetic therapy possible for many monogenic conditions very soon. Is our current system of European market authorization and reimbursement ready for the expected tsunami of gene therapies? At a recent workshop of the Netherlands ZonMw consortium on ethical, legal, and social implications of personalized medicine, we discussed the current possibilities for bringing new gene therapies to the clinic. In Europe, it is not yet clear whether the route via the European medicines agency as an advanced therapy medicinal product is the most appropriate for evaluation of highly personalized SGE applications, although this may optimally guarantee safety and effectiveness. Compassionate use may ensure faster access than the centralized procedure but does not stimulate the commercial development of products. Prescription to named patients may only provide adequate access for single patients. Temporary authorization of use may allow access to medication half a year before formal market authorization has been granted, but may also have large budget impacts. Magistral compounding under a hospital exemption may be an attractive solution for rare, tailor-made applications at an acceptable price. To approve local experimental use of a therapy on a case-by-case basis may be fast, but does not guarantee optimal safety, effectiveness, and broad implementation. We argue that alternative routes should be considered for products developed for a market of large groups of patients versus unique personalized treatments. A balance between scientific evidence for safety and effectiveness, affordability, and fast access may demand a range of alternative solutions., (© 2021. The Author(s).)

Background: Non-board-certified plastic surgeons performing cosmetic procedures and advertising as plastic surgeons may have an adverse effect on a patient's understanding of their practitioner's medical training and patient safety. The authors aim to assess (1) the impact of city size and locations and (2) the impact of health care transparency acts on the ratio of board-certified and non-American Board of Plastic Surgeons physicians., Methods: The authors performed a systematic Google search for the term "plastic surgeon [city name]" to simulate a patient search of online providers. Comparisons of board certification status between the top hits for each city were made. Data gathered included city population, regional location, practice setting, and states with the passage of truth-in-advertising laws., Results: One thousand six hundred seventy-seven unique practitioners were extracted. Of these, 1289 practitioners (76.9 percent) were American Board of Plastic Surgery-certified plastic surgeons. When comparing states with truth-in-advertising laws and states without such laws, the authors found no significant differences in board-certification rates among "plastic surgery" practitioners (88.9 percent versus 92.0 percent; p = 0.170). There was a significant difference between board-certified "plastic surgeons" versus out-of-scope practitioners on Google search between large, medium, and small cities (100 percent versus 92.9 percent versus 86.5; p < 0.001)., Conclusions: Non-board-certified providers tend to localize to smaller cities. Truth-in-advertising laws have not yet had an impact on the way a number of non-American Board of Plastic Surgery-certified practitioners market themselves. There may be room to expand the scope of truth-in-advertising laws to the online world and to smaller cities., (Copyright © 2020 by the American Society of Plastic Surgeons.)

As severe ill and incurable patients can be easy victims of misleading advertising activities for dangerous and non-effective healthcare treatments, the marketing of healthcare services are in many jurisdictions legislations tightly regulated. This article reviews the Danish regulation on marketing of healthcare services to identify which types of advertising activities that are legal. As the legislation only allows healthcare authorities to control the marketing and not the content and quality of the marketed healthcare services, their ability to intervene in serious cases of misleading advertising is limited. Misleading advertising are statements with the purpose to exaggerate or underestimate the effects and risks of healthcare services or to prevent patients from seeking conventional medical treatments. From a public health perspective, there is a need for a common EU legislation for regulation of the marketing of healthcare services as the increasing use of information technologies makes it possible for the providers to access consumers and patients directly across countries and legal systems.

Cell therapies hold significant promise for the treatment of injured or diseased musculoskeletal tissues. However, despite advances in research, there is growing concern about the increasing number of clinical centres around the world that are making unwarranted claims or are performing risky biological procedures. Such providers have been known to recommend, prescribe, or deliver so called 'stem cell' preparations without sufficient data to support their true content and efficacy. In this annotation, we outline the current environment of stem cell-based treatments and the strategies of marketing directly to consumers. We also outline the difficulties in the regulation of these clinics and make recommendations for best practice and the identification and reporting of illegitimate providers. Cite this article: Bone Joint J 2020;102-B(2):148-154.

The direct-to-consumer genetic testing (DTC-GT) market has been developing for about twenty years now, raising various debates, even controversies. But what about the regulation of these so-called "innovative" devices, but whose medical status is ambiguous? A first regulatory aspect is depending on the market itself, since the latter is currently subjected to a strong structuring process. A second regulatory aspect, more classical, is the legal one. While the DTC-GT status has long been unclear on European scale, a new text (a Regulation, not a Directive) is modifying the situation. It encourages regulation "by the market" rather than "by the medical profession", which does not imply that the latter will have no (indirect) impact on the DTC-GT market., (© 2020 médecine/sciences – Inserm.)

In 2018, Australia's Therapeutic Goods Administration introduced regulatory reforms that set stricter criteria around the regulation of products derived from a patient's own cells and tissues, posing significant implications for clinics offering stem cell treatments. We review the regulatory framework and discuss its potential commercial implications, including the ambiguities that may arise from it in practice, as well as the likely impact it will have on product development and advertising practices in the future.

The prevalence of businesses selling autologous stem cell-based interventions to patients in Australia has raised serious concerns about how weaknesses in regulation have enabled the emergence of an industry that engages in aggressive marketing of unproven treatments to patients. Little is known about how patients experience this marketing and their subsequent interactions with practitioners. This paper reports results from 15 semistructured interviews with patients and carers, and also draws upon discussion conducted with patients, carers and family members (22 participants) in a workshop setting. We explore how Australian patients and carers understand and experience these interventions, and how their presumptions about the ethics of medical practice, and the regulatory environment in Australia have conditioned their preparedness to undergo unproven treatments.

The online marketing of physicians must be measured against the same advertising regulations as conventional marketing. In this context, the Medical Professional Code of Conduct, the Medical Products Advertising Act ("Heilmittelwerbegesetz") and the Law against Unfair Competition are particularly relevant. In addition, data and personal rights aspects have to be considered in the area of online marketing. Despite increasing liberalisation tendencies, there continue to be considerable legal advertising limits for doctors, which are outlined in this article. The relatively high number of current court rulings cited in the article also shows that there are questions yet to be clarified with regard to all regulations. The judgements, which are often strongly related to the individual cases, have not answered all questions conclusively. Nevertheless, it can be stated that the legal limits of medical marketing have never been more liberal than they are now., Competing Interests: Die Autoren geben an, dass kein Interessenkonflikt besteht., (© Georg Thieme Verlag KG Stuttgart · New York.)

Objective: To assess public support for 10 potential policy initiatives to reduce sugar-sweetened beverage (SSB) consumption., Design: A 2014 historical data set, which employed a face-to-face survey in one Australian state (study 1), provided the basis for comparison with our 2017 nationally representative, cross-sectional, computer-assisted telephone interviewing population survey (study 2)., Participants: Study 1: South Australians, 15+ years (n=2732); study 2: Australians, 18+ years (n=3430)., Primary Outcome Measures: levels of support for SSB-specific policy initiatives. For the 2017 national study (study 2), demographic characteristics, body mass index, knowledge of potential harms caused by consuming SSBs and SSB consumption were included in multivariable regression analyses., Results: In 2017, all 10 potential policy initiatives received majority support (60%-88% either 'somewhat' or 'strongly' in favour). Initiatives with educative elements or focused on children received high support (>70%), with highest support observed for text warning labels on drink containers (88%) and government campaigns warning of adverse health effects (87%). Higher support was observed for SSB tax paired with using funds for obesity prevention (77%) than a stand-alone tax (60%). Support for policy initiatives was generally greater among those who believed SSB daily consumption could cause health problems in adults (4%-18% absolute difference) and/or in children (8%-26% absolute difference) and lower among SSB high consumers (7+ drinks per week; 9%-29% absolute difference). State-specific data comparison indicated increased support from 2014 to 2017 for taxation (42%vs55%; χ 2 =15.7, p<0.001) and graphic health warnings (52%vs68%; χ 2 =23.4. p<0.001)., Conclusions: There is strong public support for government action, particularly regulatory and educational interventions, to reduce SSB consumption, which appears to have increased since 2014. The findings suggest that framing policies as protecting children, presenting taxation of SSBs in conjunction with other obesity prevention initiatives and education focused on the harms associated with SSB consumption will increase support., Competing Interests: Competing interests: CLM, KE, JD, MAW, JC, DR, SJD and GW declared no competing interests. SP declares expert membership of Australian Government Health Star Ratings Committees, and JC declares membership of the Social Sciences and Economy Advisory Group of Food Standards Australia New Zealand., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Similar to the outcry over the ethics of website marketing by physicians in the 1990s, the resistance to plastic surgeons' use of social media has been loud and vehement. Many physicians, although receptive to website marketing, view social media as too radical or unprofessional. Despite the controversy, the value of social media as a communication tool for interacting with and educating patients is supported by studies showing that 65 percent of Americans and 90 percent of young adults use social media. Many plastic surgeons have been early adopters, as reflected by the articles written to help board-certified plastic surgeons use social media in academic medicine and for their practice. However, there is little guidance for young plastic surgeons who wish to use social media for professional purposes. In this study, the authors discuss the ethics and current literature on social media use by young plastic surgeons and make recommendations for how to use social media during training and after residency graduation.

Importance: Manufacturers, companies, and health care professionals and organizations use an array of promotional activities to sell and increase market share of their products and services. These activities seek to shape public and clinician beliefs about laboratory testing, the benefits and harms of prescription drugs, and some disease definitions., Objective: To review the marketing of prescription drugs, disease awareness campaigns, health services, and laboratory tests and the related consequences and regulation in the United States over a 20-year period (1997-2016)., Evidence: Analysis (1997-2016) of consumer advertising (Kantar Media data for spending and number of ads); professional marketing (IQVIA Institute for Human Data Science, Open Payments Data [Centers for Medicare & Medicaid Services]); regulations and legal actions of the US Food and Drug Administration (FDA), Federal Trade Commission (FTC), state attorneys general, and US Department of Justice; and searches (1975-2018) of peer-reviewed medical literature (PubMed), business journals (Business Source Ultimate), and news media (Lexis Nexis) for articles about expenditures, content, and consequences and regulation of consumer and professional medical marketing. Spending is reported in 2016 dollars., Findings: From 1997 through 2016, spending on medical marketing of drugs, disease awareness campaigns, health services, and laboratory testing increased from $17.7 to $29.9 billion. The most rapid increase was in direct-to-consumer (DTC) advertising, which increased from $2.1 billion (11.9%) of total spending in 1997 to $9.6 billion (32.0%) of total spending in 2016. DTC prescription drug advertising increased from $1.3 billion (79 000 ads) to $6 billion (4.6 million ads [including 663 000 TV commercials]), with a shift toward advertising high-cost biologics and cancer immunotherapies. Pharmaceutical companies increased DTC marketing about diseases treated by their drugs with increases in disease awareness campaigns from 44 to 401 and in spending from $177 million to $430 million. DTC advertising for health services increased from $542 million to $2.9 billion, with the largest spending increases by hospitals, dental centers, cancer centers, mental health and addiction clinics, and medical services (eg, home health). DTC spending on advertising for laboratory tests (such as genetic testing) increased from $75.4 million to $82.6 million, although the number of ads increased more substantially (from 14 100 to 255 300), reflecting an increase in less expensive electronic media advertising. Marketing to health care professionals by pharmaceutical companies accounted for most promotional spending and increased from $15.6 billion to $20.3 billion, including $5.6 billion for prescriber detailing, $13.5 billion for free samples, $979 million for direct physician payments (eg, speaking fees, meals) related to specific drugs, and $59 million for disease education. Manufacturers of FDA-approved laboratory tests paid $12.9 million to professionals in 2016. From 1997 through 2016, the number of consumer and professional drug promotional materials that companies submitted for FDA review increased from 34 182 to 97 252, while FDA violation letters for misleading drug marketing decreased from 156 to 11. Since 1997, 103 financial settlements between drug companies and federal and state governments resulted in more than $11 billion in fines for off-label or deceptive marketing practices. The FTC has acted against misleading marketing by a single for-profit cancer center., Conclusions and Relevance: Medical marketing increased substantially from 1997 through 2016, especially DTC advertising for prescription drugs and health services. Pharmaceutical marketing to health professionals accounted for most spending and remains high even with new policies to limit industry influence. Despite the increase in marketing over 20 years, regulatory oversight remains limited.

The scope of Implantable Drug Delivery Systems (IDDSs) comprehends a variety of sterile therapeutic implements placed inside the body to exert a certain therapeutic action for extended duration. They are classified under different categories from pharmaceutical science and regulatory perspectives. The novelty and variety of IDDSs prevent the application of a uniform regulation for all IDDS products; therefore, sponsors face regulatory challenges to register and market their products. This review investigates pharmaceutical science literature and the United States Food and Drug Administration (US FDA) regulatory guidance to find how any IDDS is classified, regulated, and introduced in the market. The regulatory classification of any IDDS, as a 'drug', 'medical device' or a 'combination product', is the cornerstone in determining the regulatory pathway, which decides the quality control requirements preceding the marketing approval. IDDSs are generally recognized as combination products as they consist of two or more regulated components (drugs, medical devices or biological products) combined prior to use to function as a single entity. Although robust and defined US FDA regulatory pathways exist for each component independent of one another, the regulatory pathways for combination products are less formalized.

Background: In recent years, experience on the application of adaptive designs in confirmatory clinical trials has accumulated. Although planning such trials comes at the cost of additional operational complexity, adaptive designs offer the benefit of flexibility to update trial design and objectives as data accrue. In 2007, the European Medicines Agency (EMA) provided guidance on confirmatory clinical trials with adaptive (or flexible) designs. In order to better understand how adaptive trials are implemented in practice and how they may impact medicine approval within the EMA centralised procedure, we followed on 59 medicines for which an adaptive clinical trial had been submitted to the EMA Scientific Advice (SA) and analysed previously in a dedicated EMA survey of scientific advice letters. We scrutinized in particular the submission of the corresponding medicines for a marketing authorisation application (MAA). We also discuss the current regulatory perspective as regards the implementation of adaptive designs in confirmatory clinical trials., Methods: Using the internal EMA MAA database, the AdisInsight database and related trial registries, we analysed how many of these 59 trials actually started, the completion status, results, the time to trial start, the adaptive elements finally implemented after SA, their possible influence on the success of the trial and corresponding product approval., Results: Overall 31 trials out of 59 (53%) were retrieved. Thirty of them (97%) have been started and 23 (74%) concluded. Nine of these trials (39% out of 23) demonstrated a significant treatment effect on their primary endpoint and 4 (17% out of 23) supported a marketing authorisation (MA). An additional two trials were stopped using pre-defined criteria for futility, efficiently identifying trials on which further resources should not be spent. Median time to trial start after SA letter was given by EMA was 5 months. In the investigated trial registries, at least 18 trial (58% of 31 retrieved trials) designs were implemented with adaptive elements, which were predominantly dose selection, sample size reassessment (SSR) and stopping for futility (SFF). Among the 11 completed trials including adaptive elements, 6 demonstrated a significant treatment effect on their primary endpoint (55%)., Conclusions: Adaptive designs are now well established in the drug development landscape. If properly pre-planned, adaptations can play a key role in the success of some of these trials, for example to help successfully select the most promising dose regimens for phase II/III trials. Interim analyses can also enable stopping of trials for futility when they do not hold their promises. Type I error rate control, trial integrity and results consistency between the different stages of the analyses are fundamental aspects to be discussed thoroughly. Engaging early dialogue with regulators and implementing the scientific advice received is strongly recommended, since much experience in discussing adaptive designs and assessing their results has been accumulated.

Background: Ethical guidelines for appropriate use of social media are beginning to be delineated. As social media becomes ingrained in plastic surgery culture, education of residents on appropriate use of social media is increasingly important. Recently, plastic surgery residency programs have begun to utilize social media., Objectives: This study characterized the trends and content of plastic surgery residency-associated Instagram accounts., Methods: Active individual residency program Instagram accounts were identified for integrated plastic surgery programs. Metrics for each account were retrieved on September 16, 2017, including date of first post, number of posts, and followers. Individual posts were analyzed for content of post., Results: Fourteen of 67 (21%) integrated plastic surgery programs were found to have active Instagram accounts. There has been an exponential growth of programs adopting Instagram since August 2015. A total of 806 posts were created. Thirty-two (3.97%) posts had intraoperative photos and only one (0.12%) showed a patient image. There were 4466 followers of plastic surgery residency programs. A linear correlation was found between number of posts and number of followers, while there was no correlation of number of followers and time since account start., Conclusions: Instagram use by plastic surgery integrated programs continues to grow exponentially, and programs are appropriately using the platform. Active use of the resident social media results in increased influence. Resident use of social media has many benefits. We propose social media guidelines for plastic surgery trainees and advocate for continued appropriate use and autoregulation by plastic surgery trainees.

Aims: To examine how pharmaceutical products that were first marketed between 1950 and 1980 were promoted to physicians through advertisements and briefly review advertising regulations and accuracy of the advertisements in the light of modern knowledge., Methods: We systematically reviewed advertisements promoting drugs for specific therapeutic areas, namely central nervous system disorders (anxiety and sleep disorders, depression, psychoses, and Parkinson's disease), respiratory disorders, cardiovascular disorders, and gastrointestinal disorders. We examined about 800 issues of the British Medical Journal (1950-1980) and about 150 issues of World Medicine (1965-1984)., Results: Advertising material was minimally regulated until the mid-1970s. Many drugs were marketed with little preclinical or clinical knowledge and some with the expectation that prescribers would obtain further data. The peak of advertising occurred in parallel with the surge in the release of novel drugs during the 1960s, but declined markedly after the mid-1970s. Advertisements generally contained little useful prescribing information. The period we investigated saw the release of many novel pharmaceuticals in the therapeutic areas we examined, and many (or their class successors) still play important therapeutic roles, including benzodiazepines, tricyclic antidepressants, phenothiazines, levodopa, selective and non-selective β-adrenoceptor antagonists, thiazide diuretics, β-adrenoceptor agonists, and histamine H 2 receptor antagonists., Conclusions: Advertising pharmaceuticals in the BMJ and World Medicine in 1950-1980 was poorly regulated and often lacked rigour. However, advertisements were gradually modified in the light of increasing clinical pharmacological knowledge, and they reflect an exciting period for the introduction of many drugs that continue to be of benefit today., (© 2018 The British Pharmacological Society.)

(1) At least 74.7 million Americans use three or more prescription drugs in a 30-day period. (2) Eighty percent of the U.S. public views prescription drug costs as "unreasonable," while 17 percent say “reasonable,” according to a recent poll. (3) An influenza drug has a cash price of $100, but a patient with insurance may pay $125 because of a “gag clause” that restricts pharmacists from disclosing price options.

A comparative analysis of assessment procedures for authorization of all European Union (EU) applications for advanced therapy medicinal products (ATMPs) shows that negative opinions were associated with a lack of clinical efficacy and identified severe safety risks. Unmet medical need was often considered in positive opinions and outweighed scientific uncertainties. Numerous quality issues illustrate the difficulties in this domain for ATMP development. Altogether, it suggests that setting appropriate standards for ATMP authorization in Europe, similar to elsewhere, is a learning experience. The experimental characteristics of authorized ATMPs urge regulators, industry, and clinical practice to pay accurate attention to post-marketing risk management to limit patient risk. Methodologies for ATMP development and regulatory evaluations need to be continuously evaluated for the field to flourish., (Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Multi-level marketing (MLM) of nutrition products has experienced dramatic growth in recent decades. 'Wellness' is the second most popular niche in the MLM industry and represents 35% of sales among all the products in 2016. This category includes dietary supplements, weight management and sports nutrition products. The aim of this paper is to analyse whether this practice is legal and ethical., Methods: An analysis of available documentary information about the legal aspects of Multi-level marketing business was performed. Ethical reflexion was based on the "principlism" approach., Results: We argue that, while being a controversial business model, MLM is not fraudulent from a legal point of view. However, it is an unethical strategy obviating all the principles of beneficence, nonmaleficence and autonomy. What is at stake is the possible economic scam and the potential harm those products could cause due to unproven efficacy, exceeding daily nutrient requirements and potential toxicity. The sale of dietary and nutrition supplements products by physicians and dieticians presents a conflict of interests that can undermine the primary obligation of physicians to serve the interests of their patients before their own., Conclusion: While considering that MLM of dietary supplements and other nutrition products are a legal business strategy, we affirm that it is an unethical practice. MLM products that have nutritional value or promoted as remedies may be unnecessary and intended for conditions that are unsuitable for self-prescription as well., (Copyright © 2018 European Society for Clinical Nutrition and Metabolism. Published by Elsevier Ltd. All rights reserved.)

Competing Interests: Competing interests: We have read and understood BMJ policy on declaration of interests and have no relevant interests to declare.

Over the past forty years, the Food and Drug Administration (FDA) has successfully restricted consumers' access to home-testing applications based on the notion that it should protect individuals from their own reactions to test results. In the 1970s, the FDA briefly denied women access to home pregnancy tests that were identical to those used in laboratories. In the late 1980s and early 1990s, it relied on concerns about consumer responses to HIV status results to justify a categorical ban on applications for HIV home-testing technology. More recently, it placed burdensome restrictions on direct-to-consumer (DTC) genetic testing companies, such as 23andMe, based on fears that consumers would make irrational medical decisions after receiving genetic variant results. Although the FDA has the statutory authority to ensure the "safety and effectiveness" of medical devices, it has expansively interpreted the term "safety" to encompass considerations of how consumers might use test results provided by purely informative devices. This Note argues that courts should not give the FDA deference on its broad interpretation of safety" in restricting home-testing devices. It documents the evolution of the expertise-based rationale for judicial deference, noting that courts typically provide scientific agencies, including the FDA, "super deference" because of the complicated nature of their work. Ultimately, courts should not defer to the FDA's interpretation of "safety" because it did not use its scientific expertise when it considered how consumers might react to HIV home-testing and DTC genetic testing results. Further, the FDA should not have the authority to make decisions based on its view of "safety" because it should not have the power to make value judgments for consumers about whether they should seek their personal medical information.

The European Union (EU) Paediatric Regulation requires that all new medicinal products applying for a marketing authorisation (MA) in the EU provide a paediatric investigation plan (PIP) covering a clinical and non-clinical trial programme relating to the use in the paediatric population, unless a waiver applies. Conducting trials in children is challenging on many levels, including ethical and practical issues, which may affect the availability of the clinical evidence. In scientifically justified cases, extrapolation of data from other populations can be an option to gather evidence supporting the benefit-risk assessment of the medicinal product for paediatric use. The European Medicines Agency (EMA) is working on providing a framework for extrapolation that is scientifically valid, reliable and adequate to support MA of medicines for children. It is expected that the extrapolation framework together with therapeutic area guidelines and individual case studies will support future PIPs. Extrapolation has already been employed in several paediatric development programmes including biological treatment for immune-mediated diseases. This article reviews extrapolation strategies from MA applications for products for the treatment of juvenile idiopathic arthritis, paediatric psoriasis and paediatric inflammatory bowel disease. It also provides a summary of extrapolation advice expressed in relevant EMA guidelines and initiatives supporting the use of alternative approaches in paediatric medicine development., Competing Interests: Competing interests: The authors declare no conflicts of interest. AMS is currently employed by Novartis., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

There are widespread concerns with the ways in which 'unproven' stem cell therapies are advertised to patients. This article explores the potential and limits of using laws that regulate advertising and promotion as a tool to address these concerns. It examines general consumer protection laws and laws and policies on advertising medical products and services, focusing on the USA, Canada and Australia. The content of existing laws and policies covers most of the marketing practices that cause concern, but several systemic factors are likely to limit enforcement efforts. Potential reforms in Australia that would prevent direct-to-consumer advertising of autologous cell therapies are justified in principle and should be considered by other jurisdictions, but again face important practical limits to their effectiveness.

Provider market power is a powerful driver of high health care costs in the United States. Despite decades of antitrust litigation and regulatory interventions, the problem has worsened and threatens to undermine the benefits of market-based policies. A critical but neglected challenge for all health care reform proposals relying on market competition to address costs is finding effective tools to address the extant market power of dominant hospitals, hospital systems, and many specialty physician practices. This article analyzes the principal market-oriented approaches that have been used in the past and proposed for the future. It argues that antitrust law has an important but constrained role to play and has proved to be especially inept in dealing with extant market power. It finds serious deficiencies in the conduct decrees imposed by some courts and in open-ended regulatory regimes such as those established by Certificate of Public Advantage laws. Although not without administrative complications, policies that target providers who possess market power by capping prices may be the most effective means to control costs and retain the benefits of a competitive delivery system., (Project HOPE—The People-to-People Health Foundation, Inc.)

The German Act on the Reform of the Market for Medicinal Products (AMNOG) will lead to rapid disappearance of many new psychotropic drugs from the market in Germany over the next few years or their not being introduced in the first place. This article lists the reasons and discusses possible solutions. In the long term, the AMNOG could not only lead to an improvement of psychopharmacology but also contribute to the development of psychiatry as a whole, especially if its standards become an international reference.

The early assessment of benefits of newly approved drugs with novel active substances or new applications, which came into force on 1 January 2011 still represents a challenge to all parties involved. This article highlights the definitions, regulatory requirements and interaction between drug marketing approval and early assessment of benefits in Germany. The constellation of an extensively harmonized European and even international drug authorization process with a predominantly national regulation of drug reimbursement situation inevitably causes friction, which could be markedly reduced through early joint advisory discussions during the planning phase for pivotal clinical trials. During the year 2015 the Federal Institute for Drugs and Medical Devices (BfArM) carried out 300 scientific advice procedures of which 34 were concerned with applications in the field of indications for the central nervous system (CNS). In comparison 98 advisory meetings were held by the Federal Joint Committee (G-BA) of which the BfArM provided advice in 12 instances and in 2 cases on CNS indications. Study design, endpoints and appropriate comparative therapies are the key issues in exchanges and discussions between the BfArM, the G‑BA and applicants. Under these aspects the BfArM and G‑BA promote an early and consistent involvement in early advice procedures regarding the prerequisites for drug approval and assessment of additional benefits.

Epilepsy is one of the most common chronic neurological diseases and represents a significant burden for patients, their families and society. In more than 75 % of patients anticonvulsant therapy consists of valproate, carbamazepine, lamotrigine or levetiracetam. There is a need for polytherapy in drug-refractory patients and they suffer from negative effects on quality of life and employment that is associated with high indirect costs. To allow a comprehensive treatment in this patient group, access to new anticonvulsants with novel modes of action is needed; however, all applications for new antiepileptic drugs failed to prove added benefits during the Pharmaceutical Market Restructuring Act (AMNOG) in Germany. One of the main reasons is the mandatory definition of a standard comparative therapy. It remains unclear whether there will be studies in the future which will fulfill the requirements of the current version of AMNOG. Observational studies after approval and marketing of new antiepileptic drugs could be better alternatives to prove added benefits for individual patients in the current German healthcare system.

Background: The treatment of patients with multiple sclerosis (MS) is associated with constantly rising costs for the healthcare system and pharmaceuticals constitute 60 % of the direct medical costs. The Pharmaceutical Market Restructuring Act (Arzneimittelmarkt-Neuordnungsgesetz, AMNOG) came into force on 1 January 2011 with the aim of limiting the costs of pharmaceuticals by obligating newly approved products to be subjected to an early evaluation of the additional benefits by the Federal Joint Committee (FJC, Gemeinsamer Bundesausschuss, G‑BA). The majority of products evaluated up to October 2015 in neurology (5 out of 8) were approved for treatment of MS., Objective: Has the AMNOG been able to fulfill the original aims?, Material and Methods: Analysis of available information on MS therapies evaluated by the FJC between December 2010 and October 2015., Results: For various reasons an additional benefit could be shown in only 2 out of 5 assessment procedures for MS drugs. It is obvious that some methodological shortcomings of the process have to be improved. Additionally requirements for pivotal clinical trials have to be harmonized with AMNOG requirements taking the best available evidence and real-life data into consideration (e.g. non-interventional studies) and a closer collaboration between the FJC, healthcare providers and the neurological societies is necessary., Conclusion: The AMNOG procedure currently only partially fulfills the original aims, which could be the reason why guidelines play a more important role for therapy decision-making than FJC decisions. As the early evaluation procedure is an adaptive process methodological shortcomings might be overcome in the future; however, this requires a much closer collaboration between the FJC and neurological societies.

Background: The European Union (EU) regulation 1901/2006 plus the implementation of pediatric investigational plans by the European Medicines Agency (EMA) have contributed to more clinical studies in pediatric psychopharmacology. A new drug market law (AMNOG) has been in force in Germany since 2011 that requires an additional process of assessment of benefits of newly authorized medications by the Federal Joint Committee (Gemeinsamer Bundesausschuss, G‑BA), which also holds for medications licensed for pediatric populations., Objectives: Summary of early assessments of benefits for newly registered compounds in the treatment of psychiatric disorders and critical discussion from the perspective of child and adolescent psychiatry., Material and Methods: Application and critical review of documents and written statements by various institutions and stakeholders related to assessment procedures and respective decisions by the G‑BA for these medications., Results and Conclusion: Clearly differing requirements for study designs and outcome parameters characterize the conditions for market authorization and for the assessment of benefits. Further adjustments to the regulations in implementing the AMNOG appear to be essential, integrating agencies involved so far, complimented by expertise from regulatory agencies and medical scientific societies.

Background: Genealogical research and ancestry testing are popular recreational activities but little is known about the impact of the use of these services on clients' biological and social families. Ancestry databases are being enriched with self-reported data and data from deoxyribonucleic acid (DNA) analyses, but also are being linked to other direct-to-consumer genetic testing and research databases. As both family history data and DNA can provide information on more than just the individual, we asked whether companies, as a part of the consent process, were informing clients, and through them clients' relatives, of the potential implications of the use and linkage of their personal data., Methods: We used content analysis to analyse publically-available consent and informational materials provided to potential clients of ancestry and direct-to-consumer genetic testing companies to determine what consent is required, what risks associated with participation were highlighted, and whether the consent or notification of third parties was suggested or required., Results: We identified four categories of companies providing: 1) services based only on self-reported data, such as personal or family history; 2) services based only on DNA provided by the client; 3) services using both; and 4) services using both that also have a research component. The amount of information provided on the potential issues varied significantly across the categories of companies. 'Traditional' ancestry companies showed the greatest awareness of the implications for family members, while companies only asking for DNA focused solely on the client. While in some cases companies included text recommending clients inform their relatives, showing they recognised the issues, often it was located within lengthy terms and conditions or privacy statements that may not be read by potential clients., Conclusions: We recommend that companies should make it clearer that clients should inform third parties about their plans to participate, that third parties' data will be provided to companies, and that that data will be linked to other databases, thus raising privacy and issues on use of data. We also suggest investigating whether a 'generational consent' should be created that would include more than just the individual in decisions about participating in genetic investigations.

Although insider trading is illegal, recent high-profile cases have involved physicians and scientists who are part of corporate governance or who have access to information about clinical trials of investigational products. Insider trading occurs when a person in possession of information that might affect the share price of a company's stock uses that information to buy or sell securities--or supplies that information to others who buy or sell--when the person is expected to keep such information confidential. The input that physicians and scientists provide to business leaders can serve legitimate social functions, but insider trading threatens to undermine any positive outcomes of these relationships. We review insider-trading rules and consider approaches to securities fraud in the health care field. Given the magnitude of the potential financial rewards, the ease of concealing illegal conduct, and the absence of identifiable victims, the temptation for physicians and scientists to engage in insider trading will always be present. Minimizing the occurrence of insider trading will require robust education, strictly enforced contractual provisions, and selective prohibitions against high-risk conduct, such as participation in expert consulting networks and online physician forums, by those individuals with access to valuable inside information.

Background: Section 114 of the Food and Drug Administration Modernization Act of 1997 regulates the promotion of health economic information by pharmaceutical companies to US health plans. Greater clarity is important given demands by payers and other stakeholders for evidence of value., Objectives: To develop hypothetical case studies of health economic promotions to examine legal and policy implications., Methods: We constructed for pedagogical purposes 10 categories of potential health economic promotions. We generated hypothetical case studies for each category, including questions about whether each might be allowable under Section 114. The case studies were developed around the following categories: 1) costing out on-label clinical end points; 2) promotion of a costing exercise to physicians working in an accountable care organization setting; 3) burden-of-illness claims; 4) economic analysis of a formulary restriction policy; 5) extrapolations to doses, populations, or settings not covered in trials; 6) adherence claims; 7) "utilization of care" as a secondary end point in randomized clinical trials; 8) costing out a competitor drug's adverse event; 9) economic analysis of comparative effectiveness claims using an indirect treatment comparison; and 10) extrapolating from surrogate to long-term outcomes in an economic model., Discussion: Most cases seem to fall into a gray zone given haziness around what constitutes "competent and reliable evidence" and "directly relate[d]" to an approved indication. In practice, it is difficult to know what the section allows given the imprecision of the statute and lack of guidance about its scope., Conclusion: Ideally, future guidance will provide clarity and flexibility., (Copyright © 2015 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.)