Coherence is the essence of everything successful. Then we add integrity.

September 2015

How 120,000 Refugees Will Be Resettled Across The EU

26. september 2015 at 7:57 | Veronika Valdova |  World Affairs

Survival guide to stem cell research and therapies: Part II

21. september 2015 at 8:00 | Veronika Valdova |  Medicine & Pharmacy
Article 11 of the Universal Declaration on the human genome and human rights (1997) states, that "Practices which are contrary to human dignity, such as reproductive cloning of human beings, shall not be permitted. States and competent international organizations are invited to co-operate in identifying such practices and in taking, at national or international level, the measures necessary to ensure that the principles set out in this Declaration are respected." [10] This wording does not prohibit cloning for non-reproductive purposes, though.

According to the International Bioethics Committees report "The Use of Embryonic Stem Cells in Therapeutic Research" (2001), "research involving human embryonic stem cells is an ethical question and it is not only the right but also the obligation of each individual society to discuss this question in its own right." The Committee promotes free and informed public debates in all countries and suggests state rather than internationally binding regulation. It requires donors' consent for the use of "surplus" embryos, review of research projects by Ethics Committees, and careful assessment of advantages and risks of alternative stem cell derivation. [11]

Development of EU policy on stem cell research
Source: Drug Development Primer: Stem cells, Arete-Zoe (2015)
The situation in Europe is much more complex and ambiguous. The Biopatent Directive (98/44/EC) excludes human embryos and cells derived from them from patentability for industrial or commercial purposes. Patentability of pre-existing cell lines is permissible, however. Moreover, the directive only affects signatories of the European Patent Convention. Research on adult stem cells, mesenchymal stem cells (MSCs) or induced pluripotent stem cells (iPSCs) is less restricted. [12] Heterogenous implementation of this legislation across the EU further complicates the issue: the stance of European countries ranges from very permissive to very restrictive.

Stem cell therapies in Europe are regulated as "Advanced-therapy medicinal products (ATMPs)": that means medicines for human use that are based on gene therapy, somatic-cell therapy or tissue engineering. [13] In December 2014, the EMA approved the first ATMP in the EU: ex-vivo expanded autologous human corneal epithelial cells containing stem cells Holoclar.[14]

National positions on human embryonic stem cell research policy
European Science Foundation: 1. National positions on human embryonic stem cell research policy and regulatory framework in Europe range from very permissive to very restrictive. The policies in the UK, Sweden and Belgium (green) are very permissive, allowing the use of embryos from different sources including those created solely for the purpose of research. In most other countries (yellow) embryonic stem cell research is permitted with restrictions (only on surplus IVF embryos). Countries marked in purple and red show various degrees of restrictive policies. The issue is not legislated at all in Austria, Poland and Ireland. Balkan countries are not included in the assessment. [15]

ClinicalTrials.Gov database: All stem cell trials registered globally (August 2015) Of 5,101 stem cell studies in total, vast majority was and is conducted in the U.S. (2,866) and Europe (1,157). The leading countries in Europe are Poland (328), Germany (287), Italy (239), United Kingdom (203) and Spain (198).

Most of the studies in the Clinical register are in early stage of research (phase I to II). Almost all (4,968) these trials involve adult stem cells. The range of conditions tested is enormous. The true success of these studies is difficult to assess, however, because only 366 of these more than 5,000 trials have posted results available for public scrutiny.
WHO register ICTRP contains 5,401 records for 4,804 trials from all over the world, main source being U.S. and European databases.

Overall, stem cell therapy remains hope for the future rather than immediate reality, with very few exceptions. Caution is highly advisable for anyone who is seeking novel and emerging treatments for currently incurable diseases. Available resources such as clinical trial databases and WHO ICTRP and the FDA register of Human Cell and Tissue Establishment offer a lot of useful information for those who need to make the right decision for themselves.

Survival guide to stem cell research and therapies: Part I

14. september 2015 at 8:00 | Veronika Valdova |  Medicine & Pharmacy
Stem cells offer tremendous promise for advancing human and animal health and medical science. Their potential is enormous: one day they may replace damaged tissues and even organs. Professionals and patients have high hopes for stem cell research because of their potential to treat conditions such as diabetes, multiple sclerosis, orthopedic degenerative diseases and injuries, spinal or brain injury, stroke, or myocardial infarction. But cell-based therapies are not the only use for stem cells. Other uses include basic research into cell division and differentiation and genetic and molecular controls, and testing new drugs. Safety of new drugs is tested on pluripotent lines; and cancer cells are used to test efficacy of potential new treatments [1].

Before use, stem cells must be manipulated so that they possess the necessary characteristics for successful differentiation, transplantation, and engraftment. This "minimal manipulation" has become the central point of stem cell regulation in the U.S. Stem cell therapies are regulated as biologics and are subject to premarket approval under the risk-based approach to approving cellular and tissue-based products. Treatments that are "minimally manipulated" are exceptions to this regulation and only have to comply with the current Good Tissue Practice[2].

Patient demand for new treatments in areas where effective cures are few and far between is enormous. It is difficult to estimate true numbers of patients seeking stem cell treatments in the U.S. and overseas. The most popular destinations include China, Mexico, Germany, the Dominican Republic, India, and Russia. Not all these countries offer equal protections to patients and standards in access to novel technologies. The global differences in regulation of research involving stem cells and novel therapies are vast.

Clinics all over the globe offer treatment of all kinds of conditions, from blindness, paralysis, multiple sclerosis, cerebral palsy, brain injuries and brain damage, and hundreds of others for sums ranging from $20,000 to 50,000. Offered treatments include allogeneic (from other humans) and xenogeneic stem cells (from animals and plants) as well as cells extracted from an individual, manipulated, and reinfused or re-implanted back into the same person (autologous stem cells). Despite uncertain effectiveness and possible severe side effects, stem cell treatments are gaining popularity. When patients are desperate, they may turn to experimental or unproven treatments:

"I may die anyway, but at least I died fighting. This is an experiment. What did I have to lose?" [3]

Some of the most egregious examples of unproven ad even dangerous stem cell treatments were discussed by Scott Pelley in CBS News investigation 60 Minutes in 2012 [4].

Development of U.S. policy on stem cell research
Source: Drug Development Primer: Stem cells, Arete-Zoe (2015)

In the U.S., the issue of stem cell research received nation-wide attention due to the utilization of surplus embryos from in-vitro fertilization (IVF) treatments as a major ethical concern. Presidential Executive Order 13505 from March 9, 2009 removed barriers to responsible scientific research involving human stem cells and changed the way the National Institute of Health (NIH) can support and conduct human stem cell research [5]. The 2009 Executive Order 13505 revoked previous Executive Order 13435 [6] of June 2007 and Presidential Statement of Aug 2001 [7] which prohibited federal funding for research on human embryonic stem cells (hESCs). In July 2009, NIH published Guidelines on Human Stem Cell Research on the donation of embryos for the derivation of hESCs, human induced pluripotent stem cells, and research involving human adult stem cells [8].

Minimally manipulated human cells and tissues and products derived from them are regulated solely under the Section 361 of the Public Health Service Act if they are intended for homologous use; if their manufacture does not involve the combination with another article, and if they do not have a systemic effect. Those that do not meet these criteria and do not qualify for exceptions are regulated as a drug, device, or biological product and have to be registered as such [9]. Whether this approach is sensible and appropriate and whether or not, and if so, how it should be changed is subject to fierce debate.

Registry of human stem cell and tissue establishments
In the U.S., human cell and tissue establishments are subject to registration. Registration details are publicly available in a database on FDA website.

Big data in drug safety

7. september 2015 at 11:36 | Veronika Valdova (@AreteZoe) |  Medicine & Pharmacy
Big data v bezpečnosti léčiv

Abstract-According to the 1997 report from Erice, Sicily, 'drug safety information should be ethically and effectively communicated in terms of both content and method', 'all the evidence needed to assess and understand the risks and benefits must be openly available', and 'exchange of data and evaluations among countries must be encouraged and supported'. To address the risk of data leaks and to facilitate real time detection of safety signals, aggregate data rather than individual case reports (ICSRs) would be more appropriate to meet the need for analysis of large volumes of information on benefit:risk profile of medicinal products by health care professionals and the public. Pharmaceutical industry can be safely left out from assessment of spontaneously reported ICSRs for potential causal relationship between suspected adverse drug reaction (ADR) and associated drug from post-approval use. Providing aggregate data to stakeholders not directly involved in patient care would be fit for purpose; and could be extended to systematic assessment of treatment outcomes from the whole population rather than detection of safety signals from small fraction of adverse drug reactions which are reported spontaneously. Information on individual case histories would remain a private matter between the patients and their health care providers. The paper makes a case for change in the way data on safety of medicines is collected, structured, analyzed, visualized, and shared; moving away from the system of active reporting of individual case reports into national and international databases, toward collection and analysis of anonymous structured summary data from health care providers, in order to allow analysis of total numbers of treated patients and treatment outcomes; including adverse drug reactions and off-label drug use, to provide meaningful, population-based, statistically valid, bias-free, real-time information on safety and efficacy of products on the market without endangering patients' privacy. Such approach would significantly reduce privacy concerns and add value for stakeholders who are interested in timely and accurate information on benefit:risk profile of medicinal products. (Read more)

Systems Approach to Training

1. september 2015 at 8:00 | Veronika Valdova |  Risk Management