Quality criteria for Real-World Data in pharmaceutical research and healthcare decision making. An Austrian Expert Consensus (Preprint)

UNSTRUCTURED Real-world data (RWD) collected in routine healthcare processes and transformed to real-world evidence (RWE) has become increasingly interesting within research and medical communities to enhance medical research and support regulatory decision making. Despite numerous European initiatives, there is still no cross-border consensus or guideline determining which quality RWD must meet in order to be acceptable for decision making within regulatory or routine clinical decision support. An Austrian expert group led by GPMed (Gesellschaft für Pharmazeutische Medizin, Austrian Society for Pharmaceutical Medicine) reviewed drafted guidelines, published recommendations or viewpoints to derive a consensus statement on quality criteria for RWD to be used more effectively for medical research purposes beyond registry-based studies discussed in the European Medicines Agency (EMA) guideline for registry-based studies

Plant of the Millennium, Caper (Capparis spinosa L.), chemical composition and medicinal uses

Background Caper (Capparis spinosa L.) is a common member of the genus Capparis, which is a perennial shrub and thorny, and a common aromatic plant in many parts of the world, especially the Mediterranean regions. Main body The aim of this mini-review was to outline the most significant health benefits of caper in both traditional and modern pharmaceutical medicine. Scientific databases such as PubMed, Science Direct, Scopus, Research Gate, and Google Scholar with emphasis on Science Direct and Scopus have been used. A review of literature was carried out using the keywords caper, Capparis spinosa, health benefits, pharmaceutical benefits, natural products, and caper bush. During the writing of the review, the time period in which the papers were published had not been selected since the focus was on significant researched selected for the areas covered in this mini-review. The main components of its aerial parts are cappariloside A, stachydrin, hypoxanthine, uracil, capparine A, capparine B, flazin, guanosine, 1H-indole-3-carboxaldehyde, 4-hydroxy-1H-indole-3-carboxaldehyde, kaempferol, thevetiaflavone, tetrahydroquinoline, rutin, kaempferol-3-glucoside, kaempferol-3-rutinoside, kaempferol-3-rhamnorutinoside, isorhamnetin 3-O-rutinoside, quercetin 3-O-glucoside, ginkgetin, isoginkgetin, sakuranetin and glucocapparin in aerial parts. The main components of root are capparispine, cadabicine 26-O-β-D-glucoside, capparispine 26-O-β-D-glucoside, and stachydrine, seeds contain glucocapparin. Traditional application of caper is for treatment of headache, fever, convulsions, diabetes, toothache, menstruation, skin disease, kidney disease, liver disease, rheumatism, ulcers, hemorrhoids and sciatica. Fruit and leaves have anti-diabetic effects, fruits have anti-obesity, cholesterol-lowering and anti-hypertensive effects, roots, fruits, stem barks and shoots have antimicrobial effects, leaves, roots and fruits contain anti-inflammatory activity, and aerial parts have antihepatotoxic effects. Conclusion On the basis of phytochemical advantages and pharmacological benefits, caper shows its importance as one of the most notable medicinal plant for prevention and treatment of various diseases, however, more researches are need on the usage of caper, especially in modern pharmaceutical science.

Indian Active Pharmaceutical Ingredient (API) Industry- An overview on Challenges, Opportunities & Regulatory prerequisites

Active pharmaceutical ingredient is a chemical compound which is most important raw material to formulate a finished pharmaceutical medicine and has a pharmacological effect. India has a long history of being heavily dependent for these raw materials on China due to one major reason i.e. Low manufacturing cost. But overdependence of APIs imports from China brought various liabilities to India including supply chain disruption and price hikes during pandemic, leading to shortage of various important APIs/KSMs. This COVID 19 widespread has solidly put the center of our country on being “Atma Nirbhar”. And this activity had brought out the strengths, market patterns and opportunities in five divisions counting Healthcare, which are basic from country’s point of view. In view of changing geo-political situation and recalibrated trade arrangement, it is crucial that India become self-reliant within the generation of APIs and KSMs, which is why decreasing the Import reliance for Active pharmaceutical ingredients (APIs) & Key starting materials (KSMs) particularly from china has been focused upon with the assistance of productive linked incentive scheme (PLIS) passed by Department of pharmaceuticals, Government of India to thrive Indian API industry. Hence, this review highlights the current state of Indian API industry, evaluates challenges, opportunities give suggestions for moving forward for self-sufficiency of APIs as well as centers on current regulatory prerequisites for Active pharmaceutical Ingredients.

Pharmacovigilance and the digital world in Italy: presentation of the results of a national survey

Background: The digital world has undergone an essential metamorphosis in recent years, making the easy sharing of information possible, including those related to pharmacovigilance and the safety aspects of pharmaceutical and other healthcare products. These new interactive ways pose both opportunities and challenges to healthcare/pharmaceutical companies. The Pharmacovigilance Working Group “Ernesto Montagna” of the Italian Society of Pharmaceutical Medicine (SIMeF) decided to carry out a survey to gain a better understanding of the role of pharmacovigilance in digital activities. Methods: The Pharmacovigilance Working Group “Ernesto Montagna” sent a questionnaire via Computer-Assisted Web Interview (CAWI) technology to the members of the Pharmacovigilance Working Group ( N = 257). The questionnaire was composed of 11 questions in four clusters exploring: (i) digital channels and projects implemented by the healthcare/pharmaceutical companies; (ii) governance tools in place for digital channels and projects; (iii) management of adverse events collected from digital channels and projects; (iv) impact of artificial intelligence on pharmacovigilance activities. Results: Ninety-three members of the Group “Ernesto Montagna” completed the questionnaire. The results show that, in the panorama of Italian healthcare/pharmaceutical companies, digital activities are ongoing, but there are still areas of uncertainty: on when a pharmacovigilance team should be involved, on the governance tools and on the guidance to be used to ensure effective governance of digital projects. Conclusion: In a scenario which is evolving very quickly, a critical factor is the availability of specific and updated regulations. Scientific societies, such as SIMeF and Farmindustria, the Italian national Pharma-Companies Association, could give a valuable contribution to the development of appropriate guidance together with the competent authorities. Plain Language Summary Results of an Italian survey on pharmacovigilance and digital world Background: The digital world allows and makes the sharing of information easy, including information related to the health status of patients and side effects of drugs. Healthcare/pharmaceutical companies are faced with both opportunities and challenges provided by such new ways of interaction among patients and healthcare professionals. The Pharmacovigilance Working Group “Ernesto Montagna” of the Italian Society of Pharmaceutical Medicine (SIMeF) carried out a survey to gain a better understanding of the role of pharmacovigilance in digital activities. Methods: The Pharmacovigilance Working Group “Ernesto Montagna” distributed a questionnaire to the 257 members of the Pharmacovigilance Working Group. The questionnaire was composed of 11 questions exploring: (i) digital channels and projects implemented by the companies; (ii) governance tools in place for digital channels and projects; (iii) management of adverse events collected from digital channels and projects; (iv) impact of artificial intelligence on pharmacovigilance activities. Results: Ninety-three members completed the questionnaire. The results show that digital activities are ongoing in the Italian healthcare/pharmaceutical companies. Despite this, there are still areas of uncertainty, in particular: on when pharmacovigilance team should be involved and on the tools and guidance to be used to ensure effective governance of digital projects. Conclusion: In a scenario that is evolving very quickly, an important factor is represented by the availability of straightforward and updated pharma-regulations and guidelines. Scientific societies like SIMeF and Farmindustria, the Italian national Pharma-Companies Association, could give a valuable contribution to the development of appropriate guidance together with the qualified authorities, in order to coordinate and standardize the approach among pharmaceutical companies.

The Association for Human Pharmacology in the Pharmaceutical Industry London Meeting October 2019: Impending Change, Innovation, and Future Challenges

The Association for Human Pharmacology in the Pharmaceutical Industry (AHPPI) annual meeting focused on impending change, innovation, and future challenges facing early phase drug development as we move into the second decade of the 21th century. The meeting opened with discussion around the technical revolution in pharmaceutical medicine over the 4 decades since the AHPPI was founded and how transformative technologies have accompanied the introduction of processes such as physiologically based pharmacokinetic modeling. During the meeting examples were presented of how in terms of the development of new therapies, the classic phases of clinical drug development are becoming a thing of the past and the lines between the phases have begun to blur, particularly in the field of oncology. The contribution that monoclonal antibodies have made to medicine and the next chapter in their design and use was also discussed. A representative of the UK’s Medicine and Healthcare Products Regulatory Agency discussed the increasing numbers of requests to approve complex innovative design trials, how novel trial designs are impacting on the traditional linear “phase” approach to drug development and the common pitfalls associated with them. Guidance was provided from a regulator’s viewpoint on what was meant by the term “novel design” and how to submit successful trial applications for such complex trials. In an Oxford-style debate, the audience discussed the motion that “there is no longer a need to include placebo subjects in early clinical trials.” The keynote speaker focused on delivering change in complex environments such as the field of drug development. The afternoon session included presentations on the challenges associated with drug product design, the complexities within non-oral dosage forms and proposed new methods of formulations for drug delivery. Presentations were also given on advances in mechanistic and computational pharmacokinetic modeling and how they have proved to be valuable tools to rationalize and facilitate the process of drug development.

Linking the Declarations of Helsinki and of Taipei: Critical Challenges of Future-Oriented Research Ethics

Expansion of data-driven research in the 21st century has posed challenges in the evolution of the international agreed framework of research ethics. The World Medical Association (WMA)’s Declaration of Helsinki (DoH) has provided ethical principles for medical research involving humans since 1964, with the last update in 2013. To complement the DoH, WMA issued the Declaration of Taipei (DoT) in 2016 to provide additional principles for health databases and biobanks. However, the ethical principles for secondary use of data or material obtained in research remain unclear. With such a perspective, the Working Group on Ethics (WGE) of the International Federation of Associations of Pharmaceutical Physicians and Pharmaceutical Medicine (IFAPP) suggests a closer scientific linkage in the DoH to the (Declaration of Taipei) DoT focusing specifically on areas that will facilitate data-driven research, and to further strengthen the protection of research participants.

Between traditional remedies and pharmaceutical drugs: prevention and treatment of “Palu” in households in Benin, West Africa

Background In Benin, malaria clinical cases, including the larger popular entity called “Palu” are evoked when people get fever. “Palu” is often self-diagnosed and self-medicated at home. This study aimed to describe the use of herbal medicine, and/or pharmaceutical medicines for prevention and treatment of malaria at home and the factors associated with this usage. Methods A cross-sectional survey was conducted in Benin in an urban and in a rural area in 2016. Around 600 households in each place were selected by using a random sampling of houses GPS coordinates of the families. The association between socio demographic characteristics and the use of herbal medicine was tested by using logistic regression models. Results In Cotonou (urban), 43.64% of households reported using herbal or pharmaceutical medicine to prevent “Palu”, while they were 53.1% in Lobogo (rural). To treat “Palu” in Cotonou, 5.34% of households reported using herbal medicine exclusively, 33.70% pharmaceutical medicine exclusively and 60.96% reported using both. In Lobogo, 4% reported using herbal medicine exclusively, 6.78% pharmaceutical medicine exclusively and 89.22% reported using both. In Cotonou, the factors “age of respondent”, “participation to a traditional form of savings” and “low socioeconomic level of the household” were associated with the use of herbal medicine. Conclusions This study shows the strong use of herbal medicine to prevent “Palu” or even treat it, and in this case it is mostly associated with the use of pharmaceutical medicine. It also highlights the fact that malaria control and care seeking behaviour with herbal medicine remain closely linked to household low-income status but also to cultural behaviour. The interest of this study is mostly educational, with regards to community practices concerning “Palu”, and to the design of adapted behaviour change communication strategies. Finally, there is a need to take into account the traditional habits of populations in malaria control and define a rational and risk-free use of herbal medicine as WHO-recommended.