User:Edouard Lassalle/sandbox

Definition and main components
Drug Value Management is the process which involves a multidisciplinary team working together, early enough, to generate the critical data at the right time with the appropriate interactions in the regulatory and competitive environment at each step of the drug's life cycle. The expected outcome is a successful launch with a sustainable access.

This approach was conceptualized by Dr. Pierre Anhoury, MD, a physician specialized in public health, geriatrics and clinical oncology.

Value Management is based on three main aspects:
 * 1) Early or Upstream Value Management
 * 2) Drug Value Vigilance consisting in transforming compulsory pharmacovigilance into a proactive real world data collection process
 * 3) Drug Value Competitive Intelligence

Context
Many governments throughout the world are experiencing financial difficulties and are therefore trying to limit their overall expenditures as much as possible. This budget austerity covers all areas of public spending including the healthcare sector. All industrialized countries have to some extent a compulsory public payer component (Medicare / Medicaid in the US, NHS in the UK...) to their health system for part of or all of their population and these instances are strongly impacted by public spending diminutions.

As these organizations see their budgets shrink or stay fixed year after year despite an ever-increasing increasing population, these payers must reevaluate the way they pay for healthcare and drugs in their respective countries. This has lead to restrictions in new drugs' reimbursement approvals as well as increased scrutiny of the criteria allowing pharmaceutical companies to obtain a mutually-beneficial reimbursed price from these organizations. Meeting efficacy and safety thresholds is no longer a guarantee that a new therapy will succeed in, or even reach, the market. Rather, patients, providers, payers and regulators frequently require companies to demonstrate that new therapies deliver distinctive value in order to gain support of providers and justify reimbursement by payers.

Non-reimbursed drugs failures

 * The divergent receptions given to two new products illustrate how profound the change in standards is for pharmaceutical companies, and the dangers of not using a value-based approach to guide new product development from the outset. The lukewarm reception and reimbursement that initially created Benlysta, a lupus therapy developed by GlaxoSmithKline and Human Genome Sciences, is a case in point. Benlysta gained Food & Drug Administration (FDA) approval in the US and European Medicines Agency (EMA) approval in 2011. Despite an annual cost of $35,000, Benlysta was eagerly anticipated by patients and investors alike . Benlysta was expected to reach peak sales of $2-$3 billion within 4-5 years  . However, Benlysta sales have yet to take off and Human Genome Sciences saw its market value drop by 70 percent as a consequence. Simply put, the companies didn’t achieve reimbursement support and missed months, and even years, in certain markets as a consequence.


 * In the US, Medicare did not add a reimbursement code for the product for the first nine months it was in the market, which resulted in complications and skepticism among doctors as to whether they would be reimbursed (some doctors were also wary that Benlysta’s benefits were modest in clinical trials) . In the EU, despite EMA approval, individual countries decided not to pay for it, which is becoming a common occurrence. The UK’s National Institute for Clinical Excellence (NICE) recommended against coverage because it was not convinced it worked better than an existing product being used off-label for lupus . NICE pointed to a lack of comparative efficacy data and determined that Benlysta did not represent “good value for money"  . Germany’s peer agency followed suit, finding “no additional benefit documented”. Benlysta may yet gain the market traction expected, but its developers have a much tougher road to travel given its perceived value profile. GSK, Lupus UK and Primary Care Rheumatology Society all submitted independent appeals to NICE challenging the organization’s appraisal of Benlysta’s benefits relative to standard care. This past September, NICE upheld the appeals and agreed to review additional data from GSK to reassess Benlysta.

Reimbursed success stories

 * Contrast this experience with that of Incyte’s Jakafi (Jakavi in Europe). In November 2011 it became the first pill approved for myelofibrosis, a rare and life-threatening disease that causes a build-up of unhealthy blood cells in the bone marrow and organs, leading to abnormally sized spleens . Most patients also experience anemia, fatigue and chronic pain . Clinical trials cited in the FDA approval noted that Jakafi did reduce spleen size, the primary goal of the trials. Moreover, Incyte and its partner Novartis also detailed quality of life and symptom improvements identified through a validated survey of patient-reported outcomes (PRO).


 * In fact, Incyte worked closely with the FDA beginning in 2008 to develop the quality of life assessment tool once Phase I/II trial results suggested a marked improvement in symptoms. In the US, the FDA cited both the primary endpoint of spleen reduction and the secondary endpoint of symptom improvement in the clinical evidence supporting the drug’s approval, allowing Incyte to discuss all benefits in promotional efforts. Without the PRO, Incyte leaders believe the drug would have faced a longer and more complex regulatory pathway to gain full approval.

Changing our approach regarding the value of a drug
The very different regulatory and reimbursement experiences of Benlysta and Jakafi illustrate the importance of companies demonstrating distinctive and overall value in order to secure reimbursement for new therapies, rather than just meeting efficacy and safety criteria. The shift in focus to value is mainly driven by is simple economics. National health services and insurers are still dealing with the after effects of the global financial crisis and health care reform legislation, both of which have squeezed funds and profit margins.

In addition, it is now possible to demonstrate and calculate drug value more accurately given scientific and structural evolutions in the industry. First, genomic science enables a higher level of new product scrutiny, and has raised expectations that the efficacy and safety of new treatments be demonstrated for individual patients, not broad classes of people. Second, payers around the world are consolidating, and larger payers can exert more pricing pressure on biopharmaceutical companies to contain costs and more buying power to demand demonstration of value-for-money and proof of positive, real-world outcomes to justify reimbursement. Most organizations have not adapted to these changes, and are using an increasingly obsolete clinical trial plan and short-lived product commercialization strategy that does not emphasize value. The results: more conditional approvals, more requests for risk evaluation and mitigation strategies and risk management plans, limited reimbursement, and poor market performance.

Yet the advent of personalized medicine and payer focus on value suggests that equally profound change is needed at pharmaceutical companies. Companies need to retool their operating models so that processes and capabilities emphasize value management as early as possible in the product development cycle to meet these new standards and expectations, including how clinical trials are shaped and conducted and the duration and content of post-launch monitoring required. The changes suggested here can help biopharmaceutical companies adopt a value management operating model where R&D and commercial functions, as well as other organizational units, expand their current focus on efficacy and safety to consider and document the economic, social and quality of life impact products have on patients’ lives.

The benefits of adopting a value management-centric operating model and related capabilities are significant—and the necessity of doing so is becoming clear as regulators, payers and providers across the globe place more emphasis on value. In the US, specialty therapeutics payers, PBMs, and specialty distributors increasingly deploy clinical pathways and other tools to limit use of innovative therapeutics to only high responder patient populations to control reimbursement costs. Similarly, Japan is seeking to control the costs of treating its rapidly aging population by resetting drug prices every two years, and making innovativeness the top criteria in setting prices. These global healthcare dynamics underscore that pharmaceutical companies must be willing and able to refine and conduct appropriate clinical trials. These trials must generate the information needed to demonstrate distinctive value in order to attain faster regulatory approval and meet the demands of public and private payers to maximize reimbursement.

Early or upstream Value Management
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Drug Value Vigilance
The current approach of pharmaceutical companies regarding Pharmacovigilance is one of begrudging compliance. Pharmaceutical companies have developped their pharmacovigilance in line with country and international requirements, providing information on adverse effects of their drugs but doing little else in terms of data analysis. In order to address current and future expectations from payers who want to know how the drugs act in the real world and not only through obviously positive phase III clinical trial endpoints, pharmaceutical companies must move from Pharmacovigilance to Value Vigilance. In a Value Vigilance environment, pharmaceutical companies collect data from Pharmacovigilance as well as through phase IV clinical trials and real life data collection to measure various aspects of the drug profile which might be difficult to estimate in smaller traditionnal randomized clinical trials:
 * Secondary effects of lack thereof of the drug
 * Benefits which had not been seen previously due to the bigger amount of patients and the presence of drug / diseases combinations that had not been tested in phase III trials
 * Quality of Life issues
 * Economical impact of the drug at the patient, local, regional, country or continent levels

Drug Value Competitive Intelligence
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Journals and specialized websites
To be completed.