Innovation in pharmacovigilance

The Israeli pharmacovigilance system was founded recently. All over the world, pharmacovigilance regulations have evolved mainly from lessons learned as a reaction to safety issues that became public health issues. This was true also for Israel which has built its regulation on the EU model, and its pharmacovigilance department six years ago, following the Eltroxin® (levothyroxin) change in the excipients; this led not only to a huge number of adverse reactions but exposed the weaknesses in pharmacovigilance organisation in Israel.

The new field of Israeli pharmacovigilance has developed quite rapidly with the obligation for pharma companies, hospitals and Health Maintenance Organisations (HMOs) to designate a Qualified Person for Pharmacovigilance (QPPV) and establish a pharmacovigilance system. Training sessions have been performed throughout the country to educate healthcare professionals on the new regulation, some of them by ISOP ISRAEL with the support of the Ministry of Health. Several programs have been created in universities in the frame of continuing education.

Today, the Ministry of Health is still focused on its priorities, which are to implement the basics of pharmacovigilance in the whole Healthcare system. The last step was the issue, only two years ago, of the risk management regulation on the European model. The pharmacovigilance department is small, with active but rather junior professionals, and pharmacovigilance inspections are still not implemented. Therefore, it cannot be expected from the Ministry of Health to both strengthen this new activity, to deal with day-to-day activities and also to be the driving force of innovation.

For historic reasons, the public health system is quite decentralised, leaving a certain degree of autonomy to hospitals and its four HMOs. Israeli citizens can freely choose and change one of the four HMOS which therefore are in competition to provide the best services.

The benefit of this decentralisation is that it leaves space to local or regional initiative.

Therefore, it is not unusual that innovations stem from a hospital, a HMO or a professional organisation.

This is the case with Sheba-Tel Hashomer Hospital, which has been rated by Newsweek as one of the ten best hospitals in the world in 2019 and is leading healthcare innovation in Israel with a significant impact abroad.

Sheba Hospital is strongly involved in drug safety with the implementation of an Artificial Intelligence (AI) solution, Medaware, monitoring and supporting the prescription through access to the Electronic Medical Record (eMR). The Institute for Health Improvement Trigger tool is currently screening the eMRs to detect potential Adverse Events through markers; for instance a sudden drop in haemoglobin in a patient with anticoagulant could mean an occult haemorrhage.

Similarly, ISOP ISRAEL, has endorsed a role of leadership since its creation, 6 years ago, which coincided with the setup of the new pharmacovigilance era in Israel.

ISOP ISRAEL and the vision of multi-stakeholder projects.

ISOP ISRAEL, the Israeli Chapter of the ISOP (International Society of Pharmacovigilance) has the mission to foster drug safety through education and research, combining the Israeli unique assets with the new trends which are shaping pharmacovigilance of tomorrow.

ISOP ISRAEL has built its strategy as follows

Multi-disciplinarity and System approach:

pharmacovigilance has remained limited far too much to industry experts and to clinical pharmacologists or clinical pharmacists. It is a common understanding in other high-risk industries, such as aeronautics and nuclear power plants, that management of risks can only be efficient when applied by a multidisciplinary team and considered across the entire system. Healthcare systems are still lagging behind; and the healthcare professions continue to act in silos. The future of pharmacovigilance lies in its becoming truly multidisciplinary. The stakeholders involved in the whole treatment process are the healthcare professionals, the patients and caregivers, the hospital management, the HMOs, the industry, the authorities and the academy.

Learning while doing

Rather than a theoretical training, multidisciplinarity is experienced through a case study.

Case study

Anticoagulants were chosen as a first example of high-risk products with many interactions between disciplines and rated one of the main classes of products involved in medications errors and hospitalisation for adverse reactions.

Tool box

ISOP ISRAEL has gathered several tools to set up its projects:

1. EU Good pharmacovigilance Practices, Risk Management and risk minimisation
2. ISMP Safe Practice Self-Assessment for anti-thrombotic therapy. ISMP, the Institute for Safe Medication Practices has been working for 30 years with the U.S. government’s FDA to prevent medication errors. They have designed tools and alert systems targeted to industry, healthcare professionals, hospital staff, lay community and authorities. The Safe Practices Self-Assessment tools allow hospitals to identify and correct weaknesses. They illustrate how pharmacovigilance can spread beyond expert pharmacologists.
3. My eReport® , mobile application, a quick and simple way to report adverse reactions
4. BeMedWise campaign ‘Talk before you take’: an organisation dedicated to patient education on medication safety, funded by FDA
5. Going on identifying tools, the next one to be integrated will be the IHI Global Trigger Tool for measuring adverse events (Institute for Health Improvement).

Pilot centres

1. ISOP ISRAEL started in advocating for its new methodology country-wide then identified hospitals ready to implement its strategy to decrease the risk of anticoagulants. Carmel Medical Center in Haifa then Maayanei Hayeshua in Bnei Braqhave been especially efficient. Setting up a multidisciplinary team, translating into Hebrew the ISMP Self-Assessment for anti-thrombotics and running it, analysing system gaps, writing and performing a CAPA(Corrective and Preventive Actions): all these steps have been implemented in less than 9 months and results have been presented in the last ISOP ISRAEL symposium, in June 2019.
2. In parallel, another innovative initiative was taking place: Superpharm, the chain of community-based pharmacies, has enrolled its pharmacists in a nationwide campaign to advise patients under anticoagulants. More than 1100 patients have been advised within a period of 4 months. Pharmacist’s intervention includes change of dosage, follow up of the renal function and dose adjustment, follow up of INR, instructions on injection practice, detection of interactions and information on the adverse reactions. The results of this experience, first-of-itskind, were presented in ISOP ISRAEL symposium.

Partnerships

This step has been crucial to build a network representing all stakeholders in Israel and abroad:

• institutions: Ministry of Health, Carmel and Maayanei Hayeshua Hospitals
• academy: Hebrew University of Jerusalem and King’s College London
• professional and patients’ associations: clinical pharmacologists, pharmacists, physicians,
• pharmaceutical companies
• US organisations: ISMP (Institute for Safe Medication Safety) and BeMedWise, dedicated to patient education

Each of these partners have contributed to bring its own angle to drug safety and achieve a real multidisciplinary think tank.

A strong Advisory Board

From the creation of the Chapter, the Advisory Board, composed of international experts, has validated the vision and the projects and actively participated in the symposium program.

Multidisciplinary and solution-oriented Symposium

The research strategy was completed by the organisation of an international symposium based on the same concepts: multidisciplinary and solution-oriented. The conference, 360° of Drug Safety was held in Tel Aviv, Israel, on 3-4 June 2019 and was attended by 174 participants from all disciplines. The main topics were the prevention of medication errors, risk communication and cases studies of risk minimisation. Several initiatives have been presented and among them the results of the ISOP ISRAEL projects. ISOP ISRAEL objectives are both to provide a toolbox ready to use to participants, and to enrol more pilot centres in Israel or abroad and spread the initiative at national level. Several start ups have presented their AI and IT solutions, Sheba hospital has shared its strategy. All stakeholders have been able to interact and share their experience.

The Israeli assets to build a unique pharmacovigilance system.

Now that the basis of the pharmacovigilance system has been founded, the next step for Israel will be to implement the new trends which are shaping the future of pharmacovigilance. In this objective Israel can benefit from key assets:

The organisation of the four Israeli HMOs can allow them to have quick and efficient dialogue with healthcare professionals and with patients. The pooling of the HMOS’ extensive and comprehensive epidaemiologic databases has started and will provide a huge amount of data [8].

Risk management activities are implemented in hospitals for more than 25 years.

As a leader in digital health, Israel has facilitated the emergence of many start-ups and companies dedicated to drug safety and using the most advanced technologies of Artificial Intelligence and machine learning.

In conclusion

ISOP ISRAEL has the ambition to play a major role in this evolution, in providing a multidisciplinary platform for experience haring, in identifying and combining new tools and platforms and in implementing innovative projects.

Israel, the Start-up nation, has the organisational, scientific, technological and cultural resources to quickly overcome the challenges and go beyond its current state to build a unique pharmacovigilance system which could serve as an example for other countries.

Declarations

Ethics approval and consent to participate: not applicable
Consent for publication: not applicable
Availability of data and material: Not applicable
Competing interests: The author declares that they have no competing interests
Funding: none
Authors' contributions: Author wrote the final manuscript

Acknowledgements

Ayalah Livneh, Pascal Grin, Dr Hesh Hershman and Yehudith Wexler for ISOP ISRAEL organization

ISOP ISRAEL Advisory Board:

Prof Herve Le Louet , president of CIOMS, Peter Pitts, President Center for Medicine in Public Interest, previously FDA Associate-Commissioner, Prof Mati Berkovitch, Safety Advisor to Israeli Ministry of Health, Prof Ronald Litman, ISMP Medical Director, Prof Nick Sevdalis, Director Implementation Sciences and Patient Safety.

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