The biomedical enterprise spans discovery, development and delivery of drugs in highly complex ways. The current therapeutics paradigm relies on cross-cultural contributions from traditional and alternative medicines, augmented by academic and corporate efforts [Citation1]. Key limitations in the formulation and development of medical strategies emerge from confines in knowledge transfer and cross-disciplinary redress to scientific and practical obstacles. Patients, payers, physicians and family members crave better health solutions, and question the value of researched interventions that often bankrupt families. This applies especially to high-risk patients with complex, co-occurring illnesses that often suffer from uncoordinated care [Citation2]. Some therapeutic effectiveness is a prerequisite, but drugs must be affordable and readily available to patients. Equity, availability and affordability represent three key factors that society must address. No solitary reason exists for the global healthcare crisis. Disparate culprits in the research-to-care enterprise include a) research system steeped in irrelevant tradition and regulation, b) clinical trial designs that limit applicability while disallowing aging, co-morbid populations, c) patients who suffer bitter realities once diagnosed, d) rising hospital, physician and drug costs with questionable benefit, e) reimbursements based on least-common denominators, f) misaligned incentives for all, and most importantly, g) a significant lack of coordinated, collaborative innovation and integration within the biomedical ecosystem. Coordinated and committed collaborative innovation holds the key to discover, develop and deliver medicines to patients [Citation1,Citation3].
Misaligned biomedical ecosystem
Biomedical ecosystems build patient navigator programs that blithely promote a broken system, instead of fixing it, and create quality vacuums while rewarding high volume, thus widening the healthcare gap. The pharmaceutical sector focuses on US FDA approvals and CMS codes with fee-for-service, assured that the market bears any price. This approach produces marginally better/equivalent p values, with worse outcomes in non-inferiority designs. Clinical trials still focus on scientific endpoints, instead of participants’ experiences and outcomes. Many ‘surrogate’ markers and laboratory tests do not explain what actually happens to patients. Meanwhile, decreased government funding, tightened pharma/biotech budgets and lay-offs and the inevitable patent cliff conspire toward an innovation crisis.
Disease is never restricted to one individual. It deeply affects and touches families, friends and colleagues, affecting quality of life and national economies alike. To embody the concept, we need to…move from ‘what's the matter’ with the patients to ‘what matters’ to our patients. For this to happen, clear empathetic communication from medical/research teams, shared decision-making and updated research methods are needed. ‘Patient-centered’ research/care must truly transform, rather than mask normal business practices.
Promising governmental partnerships
We welcome the creation of ‘Partnerships to Accelerate Therapeutics’ from the US President's Council of Advisors on Science and Technology to accelerate discovery and development of medicines through industry, academia, government and disease foundation alliances. Pharma's ‘TransCelerate BioPharma’ represents a similar vein.
The Patient-Centered Outcomes Research Institute calls for effective methods (e.g., pragmatic trials and clinical effectiveness) that tie clinical trial results to important outcomes for patients, payers and physicians. Patient-centered care also requires a new mindset and infrastructure for partnerships with patients instead of decisions made without standards. Data-sharing initiatives for research, registries and care help build a learning health system that uses science, informatics, incentives and culture to continuously improve and innovate. Additional initiatives may gain momentum, holding more promise, for example, RightCare Alliance and The Accelerated Clinical Trial Agreement.
Accelerating Medicines Partnership, coordinated by the Foundation for the NIH, is another transformative effort. The 5-year, US$230 million partnership between NIH, pharmaceutical giants and nonprofit foundations calls for collaboration, not competition, on drug discovery projects (e.g., Alzheimer's, diabetes and autoimmune disorders). Partners will share research findings together, and with the biomedical community. President Obama's BRAIN (Brain Research through Advancing Innovative Neurotechnologies) and ‘Precision Medicine’ Initiatives are other examples of collaborative innovation.
Pharma's overtures to academia
The pharmaceutical/biotech industry spends over US$140 billion on research and development in introducing 25–35 new drugs annually, but still experiences a steep innovation crisis as evidenced by long spells of drying pipeline. It takes almost 15 years, and US$3–$10 billion, including the cost of failures, to find and bring a drug to patients. The cost is too high, the length of time is long, and both are unsustainable. Clearly, we need a better way to discover and deliver effective treatments. Pharma's new business models seem to rely on the acquisition of drug candidates through alliances and mergers with smaller biotechs, and some active partnerships with academia to address key scientific questions.
Patient-derived genomic data is now approaching unimaginable levels. No single scientist, nor institute, can decipher all of the available exa-and zetta bytes of genomic data in meaningful ways. This realization led GlaxoSmithKline to open up its vault of genomic data for 300+ cancer cell lines to external scientists connected to the National Cancer Institute's caBIG (Cancer Biomedical Informatics Grid). Merck's SAGE Bionetworks, a scientists’ Facebook of sorts, offers another example of Open Science. Open innovation drug discovery initiatives, such as Eli Lilly's PD2/TD2 (Phenotypic/Target Drug Discovery), and GlaxoSmithKline's DPAc (Discovery Partnerships with Academia) represent more examples of pre-competitive ventures. Pharma's funding focus has shifted in recent years from handpicked, curiosity-driven, disease biology projects to large integrated programs with a strong emphasis on therapy development. Pharmaceutical giants have also initiated regional/global ‘science hubs’ with academia to regain biomedical innovation. The recently formed Academic Drug Discovery Consortium tracks and disseminates such corporate-academic collaboration initiatives [Citation4].
Adjusting the academic mindset
Academic scientists view pharma/biotech overtures with a mixture of appreciation and apprehension, citing that too much applied industry-sponsored research may compromise the quality of basic science. Ultimately, the corporate and academic communities must both recognize a careful balance between esoteric (basic) science and targeted (applied) research. Without support for speculative and objective exploration, truly novel therapeutic paradigms might never emerge; but without focused studies, many prospective technologies might wither on the vine. Many discoveries are driven by a focused need, as opposed to curiosity alone. Academia has recently progressed from its traditional 'systems biology' focus on target identification and validation to tool molecules (probes) against disease targets that explore therapeutic relevance. This new focus provides a welcome change, but perseverance is essential on this long, arduous road. The concept of medicinal chemistry as an unbroken continuum of drug discovery, long held in pharma, needs to take hold in academic drug hunters’ minds as well. Drug discovery operations in academia need to adopt pharma/biotech's best practices. New drug discovery paradigms should be based on complementation, not competition, between pharma/biotech and academia. Amalgamation of these divergent factors can lead to more effective collaborative-innovation models [Citation1,Citation3].
Coordinated collaborative innovation
The key to pharma/biotech solutions rests on strategic collaborative-innovation in biomedicine. Since the discovery of insulin at the University of Toronto (Canada) and its subsequent commercialization by Eli Lilly in the 1920s, academia and the pharmaceutical industry sealed a relationship that lies at the heart of drug discovery. Other outstanding examples include the discovery of Alimta™ (Prof. Edward Taylor's laboratory, Princeton University, NJ, USA) and Emtriva™ (Prof. Dennis Liotta's laboratory, Emory University, GA, USA). Fruitful collaborations, however, rarely materialize without commitment by partners. To avert healthcare crises, pharma/biotech and academia must develop common ground and work together. Pharma/biotech is all about teamwork, a concept not readily embraced by academia. Academic scientists and clinicians apply separate logic on how new drugs function. We need physician scientists to work closely with medicinal chemists to materialize their research ideas.
Collaboration is not mandatory for success. However, collaborative partnership, open or otherwise, between the stakeholders holds the key in overcoming these hurdles. Partnerships must be coordinated for operational excellence and optimal outcome, based on mutual trust and respect in the core missions of each stakeholder. In recent years, the big pharma has been exiting in droves from expensive preclinical research because of a lack of guarantee for ‘success.’ Many governmental initiatives have stepped in to fund disease biology research to fill the void, and have begun transforming academia into drug discovery behemoths. So, how confident can pharma be in pursuing the discoveries made by the academia? Not very, given the fact than many of the landmark findings in biomedical and life sciences are not reproducible. Scientific misconduct, including data falsification and peer review scams, now reaching epidemic proportions, is upsetting this applecart. Since the foundation for successful collaboration is based on mutual trust, all partners, especially the academic scientist, must work harder to rebuild and regain this confidence [Citation5].
The establishment of strong and diverse partnerships in public and private sectors is critical for patient success. To transcend external challenges for developing better medicines, we need a strong, healthy biomedical ecosystem that includes academia, nonprofit/for-profit research institutions, government agencies, pharma/biotechs and disease-oriented groups. These partnerships can lower the complexities and expense of R&D, while accomplishing much more in less time. Public-private partnerships can overcome common tensions by recognizing, respecting and accommodating differences in motivations to focus on the most disease-relevant therapeutic targets.
Building villages for better outcomes
Drug discovery takes a village of diverse expertise to develop effective solutions. First, we must stop ‘Russian Roulette’ games that follow unsubstantiated guesses on disease causality. Coordinated collaborative partnerships engaged in unraveling disease etiology will pave the path and eventually lead to effective therapeutic innovations. The much-heralded ‘open source/science’ presents new avenues to foster biomedical innovations through precompetitive strategies that can develop lower-cost, targeted therapeutics for all diseases. Changing the culture for all partners is challenging, but new models will build teamwork, clear boundaries for competition and reward innovators who embrace these changes.
The 18-year-high new drug introductions seen in 2014 made the rock-bottom approvals experienced over the past decade a distant memory, but it is the changed mindset of the pharmaceutical industry that embraced coordinated, collaborative innovation that made it all possible. While we preach for effective collaborations between pharma and academia, it is equally critical that pharmaceutical players engaged in therapeutics for a given disease join hands together for better outcomes.
It is time to refocus on the true meaning of translational research – to transform scientific discoveries into solutions for real patient problems. Timidly tweaking an existing dysfunctional system has produced little but frustration. The scope of transformation must expand to include proven communication methods that connect all physicians/scientists, while providing more empathetic coordinated care that engages patients and trial participants. The patient-doctor relationship often governs patient outcomes and satisfaction. It is an open secret that associations between better communications, outcomes and patient satisfaction result in lower hospitalization rates. Evidence-based medicine also agrees that good outcomes include meaningful results for individuals. Patient-centeredness understands that patients know how medical teams meet their needs, and their input should be included [Citation6].
Increasing demands for transparency and data-sharing include how studies are designed, conducted and summarized. Patient representatives can enhance research efforts and healthcare decisions. Efforts to improve pricing transparency could also enhance quality assessments and patient understanding. Financial transparency is currently represented only when patients are driven to bankruptcy by medical debt. The US Affordable Care Act and biosimilars have helped health systems push back against perceived overpricing and demand more ‘effective’ care, but quality care wavers without better standards.
Patients deal with dilemmas posed by this broken healthcare system everyday. It is time to center the research culture on patients and turn collaboration into the norm. An African proverb suggests 'it takes a village to raise a child.' The same is true for discovering, developing and delivering drugs to patients and thwarting the next healthcare crisis before it arises.
Financial & competing interests disclosure
The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.
No writing assistance was utilized in the production of this manuscript.
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References
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