We know that Medical Affairs and Medicines Development Professionals around the world have been working non-stop to develop vaccines, treatments, testing, and medical devices in response to the COVID-19 pandemic. To aide in the distribution of information, we have provided below important clinical trial guidance from different sources for use during this pandemic.
We wish everyone health and safety during this difficult time!
The below document was released by ACRO – Association of Clinical Research Organizations
Considerations to Support Clinical Trial Monitoring Oversight During COVID-19, 13 March 2020
The emerging coronavirus (COVID-19) situation is increasingly impacting clinical trial oversight, particularly on-site monitoring. The Association of Clinical Research Organizations (ACRO) recommends that sponsors, CROs and sites introduce emergency interim measures so that clinical trial monitoring is maintained during this period. These guidelines will ensure that data quality is unaffected, clinical trial sites are supported and that the patients enrolled in clinical trials are kept safe. The use of centralized monitoring tools and technologies can supplement and support the recommendations outlined below. These practices and tools are already in place and do not require any additional sophisticated analytical tools or dashboards. Care should be taken that any remote monitoring activities implemented are proportionate to the risks identified. Further, they should not place any extra burden on clinical trial sites.
These recommendations should be considered in the following situations: • When sites have suspended or restricted all visitors (including clinical research associates (CRAs)) from accessing medical facilities, but where patient visits are still occurring • When local health officials have implemented regional quarantines • When local CRAs are unable to travel to the sites (for personal health reasons or because of travel restrictions)
The below document was released by the European Medicines Agency (EMA).
Guidance on the Management of Clinical Trials during the COVID 19 (Coronavirus) pandemic Version 1 (20/03/2020)
The European Medicines Agency (EMA), Good Clinical Practice (GCP) Inspectors Working Group, the Clinical Trials Facilitation and Coordination Group (CTFG, a working group of the Heads of Medicines Agency (HMA)), the Clinical Trials Expert Group (CTEG, a working group of the European Commission representing Ethics Committees and National Competent Authorities) and the European Commission (EC) acknowledge the impact of COVID-19 on the health system and broader society, and the impact it may have on clinical trials and trial participants1. Extraordinary measures may need to be implemented and trials adjusted due to e.g. trial participants being in self-isolation/quarantine, limited access to public places (including hospitals) due to the risk of spreading infections, and health care professionals being committed to critical tasks. Therefore, EMA, EC and HMA strongly support the efforts of the GCP Inspectors’ Working Group for developing harmonised EU/EAA-level guidance to mitigate the negative effects of the COVID-19 pandemic on the conduct of clinical trials.
The situation is evolving, and pragmatic actions may be required to deal with the challenges of conducting research, and in ensuring the rights, safety and wellbeing of participants. The points mentioned below are intended to provide guidance for all parties involved in clinical trials during this time.
Due to the urgency, this guidance is issued without prior public consultation. The sponsors should note that due to the rapidly evolving situation further updates to this guidance are possible and likely.
The below document was released by the FDA (Federal Drug Administration)
FDA Guidance on Conduct of Clinical Trials of Medical Products during COVID-19 Pandemic
Guidance for Industry, Investigators, and Institutional Review Boards (March 2020)
I. Introduction The Food and Drug Administration (FDA or Agency) plays a critical role in protecting the United States from threats including emerging infectious diseases, including the Coronavirus Disease 2019 (COVID-19) pandemic. FDA is committed to providing timely guidance to support continuity and response efforts to this pandemic. FDA is issuing this guidance to provide general considerations to assist sponsors in assuring the safety of trial participants, maintaining compliance with good clinical practice (GCP), and minimizing risks to trial integrity during the COVID-19 pandemic.
Given this public health emergency, this guidance is being implemented without prior public comment because the FDA has determined that prior public participation for this guidance is not feasible or appropriate (see section 701(h)(1)(C)(i) of the Federal Food, Drug, and Cosmetic Act (FD&C Act) and 21 CFR 10.115(g)(2)). This guidance document is being implemented immediately, but it remains subject to comment in accordance with the Agency’s good guidance practices.
In general, FDA’s guidance documents, including this guidance, do not establish legally enforceable responsibilities. Instead, guidances describe the Agency’s current thinking on a topic and should be viewed only as recommendations, unless specific regulatory or statutory requirements are cited. The use of the word should in Agency guidance means that something is suggested or recommended, but not required.
Figure 1, left to right: Honorio Silva, IFAPP Academy President, Tim Higenbottam, current President of FPM, Ichiro Uchida (https://icpm2018tokyo.com/data/speaker26.pdf_and Aya Nakae (Osaka University)
Each year, The FPM (Faculty of Pharmaceutical Medicine) Fellows are invited to nominate exceptional individuals for Honorary Fellowship. According to the FPM’s website, Honorary Fellowship is the highest honor FPM can bestow, it recognizes the recipient’s eminence within their own field and their outstanding contribution to pharmaceutical medicine.
On the recommendation of the Fellowship and Awards Committee, the Board of Trustees, may bestow Honorary Fellowship on persons of eminence who may or may not be members of FPM, and who have made exceptional contributions in the fields of research, teaching or the practice of pharmaceutical medicine, or medical or general science, or society. Such honours are strictly limited.
On November 13, 2019 during the FPM’s Annual Awards Ceremony, held at the Royal College of Physicians, London, Dr. Honorio Silva, IFAPP Academy President was awarded with the prestigious FPM Honorary Fellowship FFPM(Hon).
Figure 2: Past Presidents of the FPM Professors Peter Stonier and Alan Boyd with Dr. Honorio Silva (on right)
The below citation was delivered by Professor Peter Stonier FRCP FFPM for Honorary Fellowship of Faculty of Pharmaceutical Medicine of the Royal Colleges of Physicians of UK.
“Professor Honorio Silva is president of the IFAPP Academy and immediate past president of IFAPP. IFAPP is the international umbrella organisation for pharmaceutical medicine, coming to its 45th anniversary next year.
After graduating in medicine at University of Buenos Aires Honorio Silva had postgraduate training in clinical pharmacology and internal medicine and conducted his clinical practice in these disciplines in his home country of Venezuela becoming assistant professor in the Department of Pharmacology Central University of Venezuela in Caracas.
However, it was in joining Pfizer in 1978 that Honorio’s professional and international career really took off. His early work focused on emerging countries in fostering a clinical research infrastructure and key projects together with medical education initiatives. This important and much needed effort soon took him beyond his day job, and into the world of academia and professional organisations. Here he gained national attention and with it many national awards for his achievements in clinical research, the development of new medicines and in medical education.
His international industry career also developed as Vice President Medical and Regulatory Affairs for Japan, Asia, Africa and Latin America. Honorio completed 30 years with Pfizer as Vice President Science and Medical Professional Development, with the global External medical affairs group.
Honorio’s career has been immersed in the international development and recognition of medicines development sciences and pharmaceutical medicine, and more recently through IFAPP in creating standards for certification in order to consolidate the discipline and profession.
None of this comes without considerable personal abilities and skills in teamwork and collaboration, building global cross functional teams, developing effective managerial and technical processes and analysing complex business and technical issues to achieve state of the art deliverables and solutions. Not to mention the dedication, energy and drive for his burning ambition – to Get The Job Done!
These qualities and attributes have not been lost on the Faculty with whom Honorio has been increasingly connected. The Faculty would like to cement this friendship and to ensure that Honorio’s important work in pharmaceutical medicine and professional development is conducted well within the tent rather than outside of it. For this reason Mr President, members and guests of the Faculty, in recognition of all his many accomplishments and a continuing expectation for more to come, I am delighted to present Prof Honorio Silva for Honorary Fellowship of the Faculty of Pharmaceutical Medicine.
A study that will provide much-needed insight for healthcare providers and pharmaceutical companies, allowing for a truly patient-centric approach with precision medicine.
“The ultimate goal of the All of Us Research Program is to collect information to lead to incredible discoveries in biomedical research and precision medicine, but along the way, we are going to transform lives. We are going to provide opportunities for people that historically have not had the opportunity to participate in research, and I think that’s a really important part of the program, and something that I feel really honored to get to be a part of.”
—Amy Taylor, regional vice president, Community Health Center, Inc.
What is the Precision Medicine Initiative?
The Precision Medicine Initiative (PMI) is a bold research effort to revolutionize how we improve health and treat disease. The PMI aims to leverage advances in genomics, emerging methods for managing and analyzing large datasets while protecting privacy, and health information technology to accelerate biomedical discoveries.
What is the All of Us Research Program?
NIH’s All of Us Research Program is a major piece of the PMI. All of Us will engage one million or more volunteers living in the U.S. to contribute their health data over many years to improve health outcomes, fuel the development of new treatments for disease, and catalyze a new era of evidence-based and more precise preventive care and medical treatment.
The above information, videos, and quotes were provided by the NIH, All of Us website. For additional information please visit: https://allofus.nih.gov/
The European Union Clinical Trials Regulation (EU CTR) 536/2014 includes a requirement for the submission of lay summaries. Study participants, advocacy groups, and, to a lesser extent, the general public have called for greater transparency in their quest for information on clinical studies. As a complement to other forms of clinical study disclosure such as registry postings and scientific publications, lay summaries may aid in the transparency of a sponsor’s clinical study results, thereby promoting trust, partnership, and patient engagement throughout the clinical study process. The data transparency field is changing rapidly; therefore, data owners should strive to stay abreast of the changes and deliver meaningful tools to their study participants and the public. Points to consider when developing lay summaries of clinical study results include regulatory drivers, the target audience, communication of complex data in a lay manner, and efficient processes for the development of lay summaries within one’s company.
Lay summaries help to provide transparency and understanding to the general public
Plain Language Summary
There is a rule in Europe that clinical studies (experiments in humans) must have a summary written in plain language. Summaries written in plain language help people who are not scientists or doctors understand complex medical information. People who participate in clinical studies, and others, may want to know information about clinical study results. Lay summaries are a way to share clinical study results, but they do not replace other ways that information is shared. Lay summary writers must think about how they can help readers understand the information. It is hard to describe the results of clinical studies in a way that everyone can understand. This article gives some ideas to think about when writing lay summaries.
Key Points
Lay summaries of clinical study results are a complement to other forms of clinical study disclosure that aid in the understanding of complex clinical study results.
The initial requirement for lay summaries began as a result of the EU Clinical Trial Regulation; however, evolving regulations and policies around the globe are shaping the future of clinical study disclosure.
Ensuring patient value should be of paramount importance when developing lay summaries.
1. What are Lay Summaries and Why are They Needed?
Lay summaries (also called layperson summaries, plain language summaries, lay language summaries, simple summaries, and trial results summaries) are plain language descriptions of the design and aggregate results of individual clinical studies (Fig.1)
Fig. 1 Excerpted pages from a published lay summary
Lay summaries are one way for industry to provide greater transparency to those interested in learning about clinical study results [2]. These documents are written specifically for study participants and the general public who have an interest in clinical study results, but who may have limited health literacy or scientific expertise. Health literacy is defined as the degree to which individuals have the capacity to obtain, process, and understand basic health information and services needed to make appropriate health decisions [3]. The goal of a lay summary is to aid study participants and the general public in understanding clinical study results. Not only does this effort help to demystify the clinical study process but it also provides the main results of clinical studies in a manner directed specifically towards people with low health literacy. The target audience is any person interested in research, and, as such, the audience is broad and may include study participants, healthcare professionals, caregivers, and the general public.
Companies providing lay summaries in advance of requirements are communicating respect for the needs and desires of the community
The data transparency field is changing rapidly, with recognition that the desires of patients and the general public may go beyond those driven by regulatory requirements. Although regulatory agencies do not currently require submission of lay summaries, some agencies have provided additional statements on the topic, as summarized below, in preparation for when the regulations come into effect. The commitment of a sponsor company to provide lay summaries in advance of regulatory requirements provides a meaningful way of communicating respect for the needs and desires of the community, particularly study participants.
The push for increased transparency in the clinical study space has presented industry and academia with an interesting choice—to proactively engage or only meet regulatory requirements. Currently, some transparency activities are not required per regulations and are implemented solely based on a company’s own policies on clinical transparency and data sharing. For example, the proactive release of clinical documents and datasets can occur through various mechanisms such as portals (e.g. clinicalstudydatarequest.com, yoda.yale.edu), registration and results disclosure (e.g. clinicaltrials.gov), or posting lay summaries of clinical study results to publicly available websites. Other transparency activities are regulatory driven, such as the release of redacted or anonymized documents for European Medicines Agency (EMA) Policy 0070.
2. What are the Current Regulatory Requirements?
2.1 European Medicines Agency: EU Clinical Trial Regulation 536/2014
The EMA initiated the call for the submission of lay summaries through the European Union Clinical Trials Regulation (EU CTR) 536/2014. Among other elements described in the regulation, sponsors must submit a summary of the results of the clinical study, together with a summary and the Clinical Study Report (CSR), irrespective of the outcome of the study. The summary must be provided in a ‘format understandable to laypersons’, with posting to the portal 1 year after the end of the trial (EoT) for studies in adults, and 6 months after the EoT for studies in the pediatric population, in all the EU languages in which the study was conducted (Fig. 2).
Fig. 2 EU Clinical Trial Regulation 536/2014potential timeline. EoT
end of trial (defined as the last visit of the last participant in all concerned
member states, or at a later point in time as defined in the protocol),
LS lay summary, Peds pediatric patients, mos months
Once the regulation is in application, all new interventional clinical studies will need to comply; however, the regulation includes three phases of implementation. Assuming the dates currently projected by the EMA, this would provide the following timescale for sponsors to submit lay summaries:
Phase 1: A 1-year introductory period where regulations are optional.
Phase 2: Spanning the second and third year of the transitory period; the regulation will be mandatory for new studies.
Phase 3: After the 3-year transitory period described above, the regulation will be mandatory for all studies (both ongoing and new studies).
To read this entire article you can download the PDF here:
“Third Strategic Pillar” of the pharmaceutical industry
Learn what McKinsey & Company has to say about the future of Medical Affairs, “A Vision for Medical Affairs in 2025”.
Are you ready for the future of Medical Affairs? In A vision for Medical Affairs in 2025, a new report released by McKinsey & Company, Medical Affairs is cited as the “third strategic pillar”[1], right along with R&D, and commercial & market access1 in the pharmaceutical industry. Essentially, Medical Affairs professionals are no longer acting as the supporting cast, they are now co-starring in the production.
As the pharmaceutical industry evolves and changes, those within it must adapt and develop the skills and competencies needed to address the emerging needs. Patients and physicians are seeking high-quality and reliable information, products, and services. Pharmaceutical companies are acknowledging the primary role that Medical Affairs Professionals play in providing this, and ultimately bridging the gap between the company and its stakeholders (physicians and patients). The need for qualified, competent, and agile Medical Affairs Professionals to fill this primary role within organizations has become apparent.
The IFAPP Academy/King’s College London, Medical Affairs in Medicines Development, Certification Program provides the training needed for Medical Affairs Professionals to not only become successful in their careers but ultimately provide a higher standard of care and service to patients and healthcare providers.
Around the turn of the century, a rather simple classification of public-private-partnerships (PPPs) in the world of medicine development sufficed. These PPPs consisted primarily of bilateral collaborations between pharmaceutical companies and academic institutes. Since then, these “simple” bilateral PPPs have been complemented by different and more diverse types of PPPs. On the one hand, PPPs emerged such as the Medicines for Malaria Venture (MMV) or the Drugs for Neglected Diseases Initiative (DNDI) with as major drivers charities, country donors, industry, and academic groups. These so-called product development partnerships (PDPs) focus on developing products for specific communicable diseases impacting health of patients in less affluent countries. On the other hand, Pharma-PPPs, such as the Innovative Medicines Initiative (IMI), emerged that focused on jointly tackling specific -precompetitive- issues in medicine development. The major players in the last category consisted of the pharmaceutical industry (large pharma), small, and medium sized enterprises (SMEs), academic institutes and–again- governmental funding programs (1, 2). Since then the background of participating stakeholders of PPPs has greatly diversified. Important new stakeholders joined the PPP consortia, including patient organizations, regulatory bodies, health technology assessment agencies, insurance companies, and IT-companies (see articles in this special issue, e.g., Aartsen et al.) All have their unique incentives to join, which makes the PPP concept more difficult to define and to evaluate in terms of its benefits. Nowadays, many PPP-flavors exist and the number and diversity continues to grow. Contributions to this special issue exemplify this current development in the PPP-world.
Added value: in the eye of the beholder or more concrete impact measures?
Early on, questions were raised about the assessment of performance and success-failure of PPPs (1–3). Performance indicators to look at were identified as: the input, the process, the output, the short-term outcome, and impact. See Figure 1 for details. The basis for this methodology was already developed and tested in other fields. What makes the Pharma-PPP case so special are the long timelines–years- to measure “impact.” The classical PPP projects have a typical running time of 4–6 years. The long-term outcome-and impact e.g., in terms of concrete new medicines can only be measured many years after finishing the project and on top of that there are many “diluting” contributing factors in the post-PPP years. Moreover, simply looking at the number of medicines developed based on the activities of a PPP significantly underappreciates the additional impact from knowledge transfer, ongoing collaborations, patents, spin-off companies formed, and last but not least the educational aspect PPP initiatives offer (See Figure 1). The true impact of the first generation of PPPs now becomes visible and we can review that according to the key performance indicators set out from the start [cf. (4, 5)].
Figure 1. Reported performance indicators to be considered in a research PPP performance measurement system, classified into 5 categories. Figure adapted from (2). 2. De Vrueh RL, Crommelin DJ. Reflections on the future of pharmaceutical public-private partnerships: from input to impact. Pharma Res. (2017) 34:1985–99. doi: 10.1007/s11095-017-2192-5 PubMed Abstract | CrossRef Full Text | Google Scholar
In that light, there is one question that was often raised in the early days and that can now be answered, i.e., the concern about the quality of the research output -read publications- of PPPs. Several studies made it clear (3, 4) that the impact of publications measured in terms of impact factor of scientific journals and number of citations of IMI and TI Pharma consortia was comparable–if not higher- than of articles published through “regular” academic groups efforts.
Sustainability: to stay or to perish?
What is the chance for a consortium to survive after finishing the first funding round? Before answering this question it should be clear whether the project, topic-wise, is supposed to be continued at all? Some projects simply do not have a horizon beyond their running time. They are set up to solve a particular -often concrete- problem. However, what if a prolonged existence is foreseen? Experience teaches us that then already in an early stage the question of sustainability should be addressed. For instance, in case infrastructure has been built up, such as databanks or test facilities, further strategies to continue activities after the first funding round should be subject of discussion early on. The article by Aartsen et al. in this special issue discusses various sustainability strategies developed for IMI projects in detail and lists “lessons learned.”
Evolution: PPP Quo Vadis?
The adoption of the “open innovation model” by the pharmaceutical industry has given the PPP concept a big push. Originally, the public partners were mainly academic and national or international public funding organizations. The large pharmaceutical industry with or without SMEs took care of the private side. Over time, the background of stakeholders in PPP consortia has diversified. Patient organizations and health insurance companies joined the consortia. Regulatory bodies such as EMA and FDA are becoming partners as well, although these institutions are very cautious to safeguard their independence from large pharma and other private stakeholders. Big IT organizations such as Google and Amazon (cloud-computing services) expanded the spectrum on the private side (Moreno et al.) as did medical device-diagnostics companies such as Siemens, Agilent, and Philips in the context of IMI. This expanding source of partners will change the character of PPP consortia. Also, the scope of activities evolved. As partners in first PPPs were jointly exploring science and collaboration in a truly pre-competitive field, a shift toward projects where partners share their strategic assets is now observed. E.g., in the IMI—European Lead Factory (see this issue: Karawajczyk et al.) industry decided to share some proprietary assets allowing competitors and public partners to boost their drug discovery programs. It demonstrates that the PPP concept has become a trusted way of working and partners now seem comfortable to evolve the model with activities closer to their core business.
These recent developments raise the question whether the original, rather narrow definitions of a PPP as mentioned at the beginning of this editorial will properly describe the PPPs in medicine development in the future. Partners outside pharma now join the game and change the dynamics and “culture.” The walls between the classical “silos” disappear rapidly.
The remaining question is then. PPP concept in the world of medicine development: Quo Vadis?
References
1. Denee TR, Sneekes A, Stolk P, Juliens A, Raaijmakers JA, Goldman M, et al. Measuring the value of public–private partnerships in the pharmaceutical sciences. Nat Rev Drug Discov. (2012) 11:419. doi: 10.1038/nrd3078-c1
2. De Vrueh RL, Crommelin DJ. Reflections on the future of pharmaceutical public-private partnerships: from input to impact. Pharma Res. (2017) 34:1985–99. doi: 10.1007/s11095-017-2192-5
3. Gunn M, Lim M, Cross D, Goldman M. Benchmarking the scientific output of the Innovative Medicines Initiative. Nat Biotechnol. (2015) 33:811–2. doi: 10.1038/nbt.3305
Keywords: editorial, public-private parternships, healthcare, innovation, medicine
Citation: de Vrueh RLA, de Vlieger JSB and Crommelin DJA (2019) Editorial: Public-Private Partnerships as Drivers of Innovation in Healthcare. Front. Med. 6:114. doi: 10.3389/fmed.2019.00114
Received: 02 May 2019; Accepted: 07 May 2019; Published: 31 May 2019.
Edited and reviewed by:Michel Goldman, Free University of Brussels, Belgium
This article was originally published on Frontiers in Medicine. Authors: Manuela Battaglia1, Pat Furlong2, Nico Martinus Wulffraat3, and Felicitas Bellutti Enders4
1Diabetes Research Institute, IRCCS San Raffaele Scientific Institute, Milan, Italy
2Parent Project Muscular Dystrophy, Hackensack, NJ, United States
3Department of Pediatric Immunology, Wilhelmina Children’s Hospital, University Medical Centre Utrecht, Utrecht, Netherlands
4Allergy Unit, Department of Dermatology, University Hospital, Basel, Switzerland
Translational medicine works through the definition of unmet medical needs, their understanding and final resolution. In this complex and multi-disciplinary process patients have always been regarded as “end-users” or no more than “data provider.” Considering that the translational practice is nowadays highly inefficient (i.e., large intellectual and economical resources are wasted with limited impact on people health) here we propose to reverse the process: start from patients, engage them, and keep them at the center. A new partnership needs to be formed between the patients and the health care professionals, as well as the treating physicians, to make the most out of the current “health resources.” New patient-centric approaches are emerging but they remain isolated phenomena often difficult to implement. Here—with this perspective—we aim at thinking differently and learning from new experiences. We will provide some successful examples of change, and we will discuss new approaches to create a radical change in the way translational medicine is managed and how this would significantly impact people health and health care systems.
Introduction
The European Society for Translational Medicine has defined translational medicine as an interdisciplinary branch of the biomedical field supported by three main pillars: benchside, bedside, and community. The goal of translational medicine is to combine disciplines, resources, expertise, and techniques within these pillars to translate efficiently and effectively scientific research findings relevant to human diseases into knowledge that is beneficial for patients via new drugs, devices, or treatment options (1). Accordingly, translational medicine is a highly interdisciplinary field and includes academia, industry, and regulatory institutions. However, patients (who are the direct beneficiaries of translational medicine) are often excluded by this complex process.
In this perspective paper, we will discuss the impasse of translational medicine, the role that patients should have in this process (with concrete examples of success) and the future directions with the aim at fostering a science that really impacts on patients’ life.
The Impasse of Translational Medicine
Translational medicine is a process fundamental for the society as it aims at developing new interventions beneficial to the patients. However, translational medicine is at a historic moment of crisis. The process is becoming unsustainable in spite of enormous technological advances, since the technological explosion has not been accompanied by a reinforcement of quality in experimental designs, especially in the discovery phases. However, there is no clear path neither for clinicians nor for scientists regarding the process of how a discovery leads to an approved drug. The high level of failure of clinical trials in Phase II/III swallows up economic resources, generates exhaustion among researchers and clinicians and, most importantly, induces frustration among patients who see their hopes for a new drug to treat their disease, disappear (2). The high failure of clinical trials can be due to the inadequate study design, incorporating endpoints that provide limited or misleading information regarding the efficacy of the test agent, to the limited reproducibility of data, or also due to the high variability between tested subjects regarding their genetic background or the heterogeneity of their disease and also their comorbidities (3). Although it is now clear that even the failure of well-designed studies benefits both researchers and healthcare systems by, for example, generating evidence about disease theories and demonstrating the limits of proven drugs (4).
The Food and Drug Administration (FDA) publishes every year a list of all the drugs released on the market 1. Backtracking the initial publication on the mechanism or molecule leading to drug development shows—for the drugs released between January and September 2018—a median interval of 10 years (range: 5–37 years) before the drug is reaching the patient. This is becoming unsustainable as it creates tremendous social distress. At a time of global financial crisis, citizens perceive that vital resources are not being used efficiently and scientists fear to enter in a career path that is uncertain and not properly rewarded.
Thus, there is a great need to reconsider the translational medicine process and we do believe that moving the patients from “end-users” to “engaged collaborators” would transform them into agents of change. The standard business model is indeed to speak to the consumer. Apple for instance understands its consumer: it must first identify the customer, talk about the product and ask if the intended consumer would value the product. Is it any wonder why Apple is the first billion-dollar company? They know their consumer! In translational medicine, this concept is ignored. Patients are the ultimate users of health technologies and they can advocate and promote models for patient involvement among other stakeholders. Nothing will facilitate the dialogue among scientists, clinicians, and society more effectively than the creation of a pathway, constructed together, and bound by a common objective. This should lead to improved translational medicine efficiency and reduced waste of resources and energies.
Current Advances
The doctor-patient relationship in western countries has significantly evolved over the years. Prior to the last two decades the relationship followed a paternalistic model, where the patient sought help and the doctors used their skills to choose the necessary interventions or treatments to restore or improve patients’ health. Decisions of the doctors were silently complied by the patient (5). The social system has been challenged over the last 20 years: society has changed (being now multicultural), access to information is broader (social), media allow easier contact between patients and thus facilitated creation of patient’s organization. Therefore, critics have emerged, demanding a more active, autonomous and thus centered role for the patient who advocates greater control, reduced physician dominance, and more mutual participation.
This has led to the idea of the Shared Decision Medicine (SDM), which is a process promoted by the Institute of Medicine (IOM) as part of the strategy to improve the quality of health care in the United States. The IOM recommended that healthcare should be customized based on the patient’s needs and values, the patient should be given adequate knowledge and control to make decisions that affect his/her health, patients and healthcare providers should communicate and share information, and patients should receive information that allows them to make informed decisions. To this end, SDM is the joint involvement of patients and healthcare providers in making healthcare decisions that are informed by the best available evidence in regards to possible options, potential benefits and harms, and that consider patient preferences and values. SDM ensures patients get no more and no less of the care they need and want (6, 7). However, despite attention to principles and competences, there remains a lack of clear guidance about how to accomplish SDM in routine practice. Studies have not yet addressed the question about the impact on professionals. There might be the need to coach patients to be able to assess the value, risks, benefits, and burden of interventions. For organizations, a consistent shared decision-making might change patient experience evaluations and lead to a “satisfied patient” and fewer complaints or even legal issues. Clear outcome measurements of shared decision-making are needed as they would provide a more substantive evidence base to guide implementation (6).
Another, more recent, approach to bring the patients closer to the science that could impact their life is the “plan S.” Research funders from France, the United Kingdom, the Netherlands, and eight other European nations have unveiled a radical open-access initiative; they will mandate that, from 2020, the scientists they fund must make resulting papers free to read immediately on publication. The scientific papers would have a liberal publishing license that would allow anyone to download, read it or otherwise reuse the work leading to a science no more locked behind paywalls and freely available for everybody (8).
Increasingly, funding opportunities for translational biomedical research require studies to engage community partners, patients, or other stakeholders in the research process to address their concerns. However, there is little evidence on strategies to prepare teams of academic and community partners to collaborate on grants. A well-planned and feasible educational program designed to help community organizations and academic institutions to build infrastructure for collaborative research projects using a partnered approach is needed and some institutions are already investing in this important activities (9, 10).
Industry is today also very open to view patients as close collaborators and aims at connecting with them throughout the innovation journey, starting with validation of new concepts to the design of patient-centric trials. The customer journey is a term from marketing, describing the 5 cycles, which a client passes through before he decides to buy a product, or in medical terms, before he decides for one or the other therapy. Five phases mark this journey: awareness, favorability, consideration, intent to purchase (or in medical terms, intent to treat), conversion (decision to treat). For most pharma companies, this represents a major shift in thinking. It requires putting not the product but the customer at the center of the launch, and addressing customers’ emotional and behavioral needs as well as their clinical ones.
There are also tangible examples of success on how to move the patients at the center of the translational medicine process. Here we report two specific cases.
The Remarkable Story of a Mother and the Parent Project Muscolar Dystrophy
When doctors diagnosed her two sons, Christopher and Patrick, with Duchenne muscular dystrophy (DMD) in 1984, Pat Furlong didn’t accept the therapeutic nihilism, the fatalistic message from their doctor “there is no hope and little help.” DMD is the most common, lethal genetic disease diagnosed in childhood; it is an aggressive and ultimately fatal muscle wasting disease that primarily affects boys and it results in a progressive loss of muscle strength. Individuals with DMD lose ambulation in the early teens, require ventilation in the mid-teens and die before reaching the 3rd decade. Families who receive the diagnosis are in a race against time. They await new knowledge and scientific breakthroughs, possibilities to slow the degeneration. As of today, steroids are used to slow the decline, but there are no cures for DMD. In 1994, together with other parents, Pat Furlong founded Parent Project Muscular Dystrophy (PPMD) to change the course of the disease and ultimately end DMD. PPMD is today the largest most comprehensive non-profit organization in the United States focused on finding a cure for DMD 2. In her quest for a cure, she first realized that there simply wasn’t enough research into the disease and too many questions being left unanswered. Her first efforts focused on small investments in academic research and leveraging those investments. Due to the rarity of the disease (1 in 4600−5600 boys) and hence lack of potential profits there had been little interest at the onset from major pharmaceutical companies. Early in the fight, PPMD realized that the greatest source of advancement in basic science surrounding DMD would be through an investment by the National Institutes of Health (NIH) and related agencies. In 2000, the Duchenne community, through PPMD, employed a firm to lobby on their behalf in Washington DC and scored major legislative success with the introduction of legislation, intended to require government agencies such as NIH to significantly increase its investment in and coordination of research into the muscular dystrophy’s. That same year, at the insistence of PPMD, NIH held a scientific workshop on Duchenne, bringing in scientists from all over the world to advance the cause. This was a workshop of major significance in which attending scientists’ and researchers came to the realization that with the knowledge of the genetic basis of the disease and through multidisciplinary collaboration, something could be done to improve the quality of life and extend the lifespan of boys with DMD. On the tails of the earlier success with NIH, PPMD continued its Washington DC advocacy agenda and achieved another stirring victory. In December 2001, the Muscular Dystrophy CARE ACT was signed into law. This legislation dramatically increased NIHs investment in Muscular dystrophy research (from ~$17 millions to over $750 millions), including the funding of six Centers of Excellence. All of that, in addition to the earlier orphan drug act of 1983 incentivizing companies to invest in rare disease research, resulted in significant breakthroughs and new knowledge to fully characterize the pathology of DMD and to encourage industry interest in targeting relevant pathways. Today there are more than 40 ongoing clinical trials, whereas in 1999 there was 1 trial. Additionally, today there are more than 45 pharmaceutical companies investing in DMD. Current market estimates an 8-Billion-dollar investment in drug development. PPMD is currently working with FDA to develop a Master Protocol to enable access to trials across the Duchenne community, potentially leading to combination therapies and reach the highest priority of families (Figure 1).
Patient advocacy has come of age. Foundations focused on a specific disease provide substantial investments in research, organize the patient community, collect data to better understand disease progression, support the development of biobanks, inform regulatory interactions and assist patients navigate the healthcare environment. Advocacy efforts lead the ecosystem of research, therapy development, access and reimbursement. Her sons lost their battle with DMD in their teenage years, but Pat Furlong continues to fight—in their honor and for all the community to this day.
The Development of a Patient Council Within a Clinical Department
Another, yet different, example of success comes from the Department of Pediatric Rheumatology at the Wilhelmina Children’s University Hospital in Utrecht (The Netherland) focused on the study and cure of Juvenile idiopathic arthritis (JIA). JIA is the most common chronic rheumatic disorder in children and is a major cause of short-term and long-term disability. JIA is defined as having an inflamed joint before the age of 16 without a clear cause that persists for more than 6 weeks; it is a chronic disorder, which if neglected, can lead to serious complications.
In developing a network for biological research for patients with Childhood Arthritis doctors and scientists at the Wilhelmina Center of Excellence strongly think that input from and collaboration with patients and patient organizations is crucial. Patients, their parents, doctors and researchers all share the same common goal, namely that progress in basic science is translated in real tangible products for patients with childhood arthritis. In 2013 a patient council was formed in this Department. Together with professionals the JIA patient council explore research priority setting by reviewing the research topics, safety and efficacy of immunizations, as well as stopping medications. In addition to this, a jointly written application was obtained for a project with focus groups for patients that was also led by a parent. The patient council selected a topic which was the most frequent concern expressed by patients: the uncertainty patients feel due to the impact of the unpredictable course of their disease (pain, relapses) in their activities of daily life (activities at school for younger children and later work, sports and social contacts). Focus groups further analyzed the effects of the unpredictable course of the disease. Information was written for websites and two youtube movies were made. The group made of Dutch organizations of patients, parents and clinicians will collaboratively develop a research agenda for JIA, following the James Lind Alliance (JLA) methodology 3. The JLA is a non-profit making initiative established in 2004 and it brings patients, caregivers and clinicians together in Priority Setting Partnerships (PSPs) to identify and prioritize the top 10 uncertainties, or unanswered questions, about the effects of treatments. The aim of this is to make sure that health research funders are aware of the issues that matter most to patients and clinicians. In this process the input from clinicians, patients and their caregivers will be equally valued. Additionally, focus groups will be organized to involve young people with JIA. The involvement of all contributors will be monitored and evaluated. In this manner, the project will contribute to the growing body of literature on how to involve young people in agenda setting in a meaningful way.
This approach, despite still at its infancy, will inform researchers and research funders about the most important research questions for JIA and this will hopefully lead research agenda for research that really matters (11).
Current Obstacles and Future Directions
The examples provided show how patients and their care givers can be the catalysts of a change that is highly needed in translational medicine but they remain, as per today, sporadic cases led by unique human beings or by particularly inspired institutions. Many obstacles remain. Qualitative research showed that the involvement of patients and caregivers is challenging: real co-design does not happen by itself (12). First, specific educational programs are needed to improve the process of shared decision-making, for both partners, the patient and the physician. These programs are missing and importantly clinicians are often limited in their time-management. Educate and engage patients is a time-consuming process but health insurances—as well as hospitals—push more and more to reduce the time spent with patients, as costs of medication, exams, and personnel are dramatically increasing.
Scientists are even farther away from this process, as they often do not have direct contact with the patients. Current criteria for promotion in the medical field still rely heavily on individual research output such as high impact publications, h-index, grants, and invited lectures. There is tremendous pressure and on top of this pressure, there is really no space for a patient-centric view that needs time, patience and dedication. Especially in a system where these activities are not properly recognized and, as a consequence, rewarded. To change this, institutions need to ensure that their tenure and promotions systems are able to evaluate and recognize the contributions investigators conducting translational medicine make. Many institutions are working in this direction and, for instance, signed the Declaration on Research Assessment (DORA). DORA recognizes the need to improve the ways in which the outputs of scholarly research are evaluated. The declaration was developed in 2012 during the Annual Meeting of the American Society for Cell Biology in San Francisco4[4]. It is a worldwide initiative covering all scholarly disciplines and all key stakeholders including funders, publishers, professional societies, institutions, and researchers. It is a first step toward assessing research based on its own merits rather than on the basis of the journal in which the research is published.
In conclusion, translational medicine is a very complex branch of medicine. The constant challenges of teaching, researching, publishing, and competing for limited sources of funding, coupled with pursuing career aims and ambitions, can seem daunting. On top of this, we are also adding the patient-centric4 view, which adds another level of complexity. However, we believe that once the obstacles are overcome, the real inclusion of patients in the process of translational medicine will improve healthcare delivery to patients.
Author Contributions
MB conceived the topic, contributed to the topic discussion and wrote the manuscript. PF and NW contributed to the topic discussion and contributed to manuscript writing. FB contributed to the topic discussion and wrote the manuscript.
Funding
MB is supported by research grant from JDRF, NIH and the Italian Ministry of Health.
Conflict of Interest Statement
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
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2. Hwang TJ, Carpenter D, Lauffenburger JC, Wang B, Franklin JM, Kesselheim AS. Failure of investigational drugs in late-stage clinical development and publication of trial results. JAMA Intern Med. (2016) 176:1826–33. doi: 10.1001/jamainternmed.2016.6008
3. Lowenstein PR, Castro MG. Uncertainty in the translation of preclinical experiments to clinical trials. Why do most phase III clinical trials fail? Curr Gene Ther. (2009) 9:368–74. doi: 10.2174/156652309789753392
7. Elwyn G, Frosch D, Thomson R, Joseph-Williams N, Lloyd A, Kinnersley P, et al. Shared decision making: a model for clinical practice. J Gen Intern Med. (2012) 27:1361–7. doi: 10.1007/s11606-012-2077-6
9. King KM, Pardo Y-J, Norris KC, Diaz-Romero M, Morris D, Vassar SD, et al. A Community-academic partnered grant writing series to build infrastructure for partnered research. Clin Transl Sci. (2015) 8:573–8. doi: 10.1111/cts.12327
10. Paberzs A, Piechowski P, Warrick D, Grawi C, Choate C, Sneed G, et al. Strengthening community involvement in grant review: insights from the Community-University Research Partnership (CURES) pilot review process. Clin Transl Sci. (2014) 7:156–63. doi: 10.1111/cts.12141
11. Schoemaker CG, Armbrust W, Swart JF, Vastert SJ, van Loosdregt J, Verwoerd A, et al. Dutch juvenile idiopathic arthritis patients, carers and clinicians create a research agenda together following the James Lind Alliance method: a study protocol. Pediatr Rheumatol Online J. (2018) 16:57. doi: 10.1186/s12969-018-0276-3
12. Abma TA. Dialogue and deliberation: new approaches to including patients in setting health and healthcare research agendas. Action Res. (2018) 22:147675031875785. doi: 10.1177/1476750318757850
Citation: Battaglia M, Furlong P, Wulffraat NM and Bellutti Enders F (2019) Improving the Translational Medicine Process: Moving Patients From “End-Users” to “Engaged Collaborators”. Front. Med. 6:110. doi: 10.3389/fmed.2019.00110
Received: 10 October 2018; Accepted: 03 May 2019; Published: 21 May 2019.
Edited by:Wu Yuan, Johns Hopkins Medicine, United States
Reviewed by:Shi-Cong Tao, Shanghai Sixth People’s Hospital, China Marian Klinger, Opole University, Poland
The below excerpt is from an article originally published on the Frontiers in Pharmacology website. To check out the full article click here.
The development of new medicines today, requires a multi-professional workforce, both in industry and the clinical research arena. Pharmaceutical physicians (PPs) and medicines development scientists (MDS) need a certain level of competence, achieved through on-the-job experience, with a postgraduate education foundation and continuous professional development programs. In order to assess the self-perception of competence, education and training needs, an on-line questionnaire based on the seven domains of competence, developed by IFAPP-PharmaTrain, was prepared and distributed among PPs and MDS members of IFAPP’s affiliated professional associations in countries with facilities for postgraduate education. The data collection was run over a fixed period of three months in Japan, Italy, Brazil, and Spain during 2017. Results indicate low but variable levels of perceived competence for the various domains as well as seniority in the job. All respondents declared a significant need for continuing professional development in all domains. These results corroborate and support the continuous efforts, put in place by IFAPP and the PharmaTrain Federation, to foster the development of accredited education and training among professionals involved in medicines development.
Introduction
For some time now, the biopharmaceutical industry has been the key link between basic biomedical discovery and the emergence of novel medicines that prolong or improve life. However, the industry faces several ongoing and emerging challenges, including technical knowledge gaps, limitations in clinical testing, lowered productivity, higher development costs, increased regulatory requirements, growing payer pressures and patent expiration.
The lack of an adequately sized and appropriately trained multi-professional workforce, both in the industry and the clinical research field, is also a significant part of the problem. There is a perceived mismatch between the profiles and abilities of graduates from academic programs in healthcare professions, and the changing needs of the various health systems around the world. As a possible solution to achieving a transformative learning, an outcomes-based education, or competency-based education (CBE), has been proposed (Silva et al., 2013). Competent professionals would be able to perform their specific responsibilities effectively, such as bringing and maintaining new medicines to the marketplace. A need for competency-based education and training has been identified in the United States, Europe, and Latin America (Dubois et al., 2016).
These respective professional groups have been left with the responsibility to define the competencies needed to perform their function effectively. Competencies can be clustered in domains and can be learned through proper postgraduate education or continuing professional development (CPD) (Sonstein et al., 2014).
The International Federation of Associations of Pharmaceutical Physicians and Pharmaceutical Medicine (IFAPP)1 and the PharmaTrain Federation (PharmaTrain)2 assumed the task of producing the defined core competencies to orientate Pharmaceutical Medicine and Medicines Development as a discipline and profession. Three areas, seven domains and 57 core competencies at the cognitive level, were identified (Silva et al., 2013). The domains have been summarized in a Statement of Competence.
In addition to serving as a template for job profiles and portfolios, the domains can be used to identify general education and training needs. Based on these premises, an international survey among members of the IFAPP national member association was designed using an online questionnaire. Stakeholders were asked about their self-perception of competence and the need for education and training. The results were then assessed to identify gaps, in order to address the potential need for future development of pharmaceutical physicians and medicines development scientists.
By: Kyoko Imamura1*, Domenico Criscuolo2, Anna Jurczynska3, Gustavo Kesselring4, Peter Stonier5, Tatsushi Tsuda1 and Honorio Silva6
An article from Kenneth Kaitin, PhD, Professor and Director at Tufts Center for the Study of Drug Development.
This article was originally published by Tufts CSDD Insider.
Kenneth Kaitin, PhD, Professor and Director at Tufts Center for the Study of Drug Development.
Earlier this week, I was interviewed by a National Public
Radio affiliate for a segment to be aired in the coming days on whether high
drug development costs justify the high prices of many new pharmaceutical
products. As many of our readers are aware, Tufts CSDD is known internationally
for its series of studies estimating the true cost of pharmaceutical R&D.
Our latest study (DiMasi et al, J Health Econ 2016;47:20-33) determined that the
fully-capitalized cost to bring a new drug to market, including the cost of
failures, is $2.6 billion, a 145% increase in constant dollars over our
previous report published in 2003.
At more and more public and professional forums these days,
I find myself addressing a common misconception about the relationship between
R&D costs and drug prices. Much of this misunderstanding, I believe, comes
from confusing messaging by the pharmaceutical industry. For example, when
asked to explain why drugs are so expensive, the response is often, because it
costs so much to develop new drugs (“The Tufts Center says it costs $2.6
billion to develop a new drug!”). On the other hand, when asked to provide the
actual cost data for a specific drug, the response is often, “The cost to
develop a drug has no bearing on the price of that drug.” A sane individual
might ask, “How can both of these responses be correct?” The bottom line is
that they both ARE correct.
As I explain it, average R&D costs represent the cost to
maintain R&D operations. In other words, across a company’s marketed drug
portfolio, average prices must be high enough for the company to generate
sufficient revenue to maintain its R&D operations and (hopefully) develop
tomorrow’s breakthrough drug. An individual drug’s price, however, typically
reflects that drug’s perceived therapeutic and economic value, the competitive
landscape, and the ability to obtain reimbursement. In other words, drug
pricing is not unlike pricing of any other product.
The public debate over drug prices and the cost of
healthcare in general is certain to continue into the foreseeable future.
Greater transparency on how companies determine drug prices and how that
relates to R&D costs would go a long way toward improving public understanding
and furthering the discussion.
This article excerpt was originally published on the PhRMA website.
On January 31st, 2019, the Pharmaceutical
Research and Manufacturers of America (PhRMA) elected three new officers to its
board of directors. Olivier Brandicourt, CEO, Sanofi, became chairman of the
PhRMA board of directors. Giovanni Caforio, M.D., chairman of the Board and
CEO, Bristol-Myers Squibb Company was named chairman-elect and David Ricks,
chairman and CEO, Eli Lilly and Company assumed the role of board treasurer.
Brandicourt formerly held the position of
chairman-elect of the board and succeeds Robert A. Bradway, chairman and CEO,
Amgen Inc. as PhRMA board chairman.
Brandicourt has served as CEO, Sanofi,
since April 2015. Brandicourt joined Sanofi from Bayer Healthcare AG where he
served as CEO from 2013 until 2015. Prior to joining Bayer Healthcare,
Brandicourt worked at Pfizer for 13 years, where he served as a member of the
executive leadership team and as president and general manager of the emerging
markets and established products business units. He is an honorary member of
the Royal College of Physicians in London and a board member of the Children’s
Aid Society in New York. Brandicourt studied medicine at the University of
Paris V where he specialized in infectious diseases and tropical medicine and
holds an advanced degree in cellular and immunological pathophysiology from the
Paris Descartes University. Brandicourt also received a master’s degree in
biology from the University of Paris XII.
Dr. Caforio has served as CEO of
Bristol-Myers Squibb since May 2015 and became chairman of the board of
directors in May 2017. Dr. Caforio received his medical degree from the
University of Rome and joined Bristol-Myers Squibb in Italy in 2000. He
advanced through a series of roles in Europe and the United States, becoming
president of the U.S. commercial organization in 2011. He was named chief
commercial officer in 2013 and became chief operating officer in 2014. Dr. Caforio
is a member of the Board of Trustees of Hun School of Princeton and a member of
the Business Roundtable and the CEO Roundtable on Cancer.
Ricks has served as CEO of Lilly since
January 1, 2017 and became chairman of the board of directors on June 1, 2017.
A 20-year Lilly veteran, he previously served as president of Lilly
Bio-Medicines and as president of Lilly USA, the company’s largest affiliate.
Ricks also served as president and general manager of Lilly China, operating in
one of the world’s fastest-growing emerging markets, and general manager of
Lilly Canada after roles as director of pharmaceutical marketing and national
sales director in that country. He is the president of the International
Federation of Pharmaceutical Manufacturers & Associations (IFPMA) and
serves on the board of the Central Indiana Corporate Partnership, the Elanco
Board of Directors and the Adobe Board of Directors.
Ricks is a graduate of Purdue University and
earned his MBA from Indiana University.
