Evidence-Based Decision-Making 8: A Primer on Health Policy for Researchers.

There is a growing expectation that research will be used to inform decision-making. It is important for researchers to understand how health policy is developed and the different ways they can influence the development of policy.Public policy is developed to resolve identified problems. Health policy is a subset of public policy and is typically concerned with issues related to the health of populations either from a service delivery perspective or from a broader public health and social determinants of health perspective. The policy planning algorithm is well established and follows the basic decision-making framework: problem identification, policy formulation, implementation, and evaluation. A variety of government and nongovernment stakeholders engage in complex debates to identify and resolve policy issues. In this chapter, we explore how researchers can use their research to influence the development of health policy. Knowledge translation strategies focused on communicating research to policy-makers require considerable thought and planning.

Lawmakers' use of scientific evidence can be improved.

Core to the goal of scientific exploration is the opportunity to guide future decision-making. Yet, elected officials often miss opportunities to use science in their policymaking. This work reports on an experiment with the US Congress-evaluating the effects of a randomized, dual-population (i.e., researchers and congressional offices) outreach model for supporting legislative use of research evidence regarding child and family policy issues. In this experiment, we found that congressional offices randomized to the intervention reported greater value of research for understanding issues than the control group following implementation. More research use was also observed in legislation introduced by the intervention group. Further, we found that researchers randomized to the intervention advanced their own policy knowledge and engagement as well as reported benefits for their research following implementation.

Evidence Supporting the Value of Surgical Procedures: Can We Do Better?

There is an acknowledged need for higher-quality evidence to quantify the benefit of surgical procedures, yet not enough has been done to improve the evidence base. This lack of evidence can prevent fully informed decision-making, lead to unnecessary or even harmful treatment, and contribute to wasteful expenditures of scare health care resources. Barriers to evidence generation include not only the long-recognized technical difficulties and ethical challenges of conducting randomized surgical trials, but also legal challenges that limit incentives to conduct surgical research as well as market-based challenges that make it difficult for those funding surgical research to recoup investment costs. These legal and market dynamics differ substantially from those surrounding new drug or device development. Nevertheless, obstacles could be overcome and overall expenditures could be reduced if a share of federal health care agency budgets were reallocated to generating randomized trial data, standardizing outcome measures, and conducting observational studies analogous to those that have been facilitated for drugs via the Food and Drug Administration's Sentinel Initiative. Until better quality evidence is available, ethical principles require adequate disclosure of the limited evidence base supporting current surgical procedures.

The pervasiveness and policy consequences of medical folk wisdom in the U.S.

Medical folk wisdom (MFW) refers to widely held, but factually inaccurate, beliefs about disease, immunity, pregnancy, and other medically-relevant topics. Examples include the idea that fasting when feverish ("starving a fever") can increase the pace of recovery, or that showering after sex can prevent pregnancy. The pervasiveness of MFW, and whether or not it-like other forms of medically-relevant misinformation-shapes Americans' health behaviors and policy preferences is an important and under-studied question. We begin this research by proposing and validating a novel measure of MFW; including a short-form scale suitable for administration in public opinion surveys. We find that nearly all Americans-irrespective of socio-economic status, political orientation, and educational background-endorse at least some aspects of MFW. Concerningly, and consistent with the idea that folk wisdom challenges scientific expertise, we additionally find that those highest in MFW tend to place less value on medical expertise and the role experts play in shaping health policy. However, this skepticism does not appear to translate to peoples' health actions, as MFW appears to have an inconsistent effect on public participation in healthy behaviors.

Publicly accessible evidence of health-related quality of life benefits associated with cancer drugs approved by the European Medicines Agency between 2009 and 2015.

OBJECTIVE: Health-related quality of life (HRQoL) is one of the most important patient-relevant study end-points for the direct measurement of the benefit of cancer drugs. Therefore, our aim is to detect cancer indications with no published information on HRQoL at the time of European Medicines Agency (EMA) approval and monitor any reported HRQoL evidence updates after at least three years of follow-up. METHODS: We included all cancer indications that were approved by the EMA between January 2009 and October 2015. Our main sources of information were the EMA website, clinicaltrials.gov and a systematic literature search in PubMed. Information on HRQoL outcomes was extracted alongside evidence on median overall survival. RESULTS: In total, we identified 110 indications, of which more than half (n = 58, 53%) were lacking available information on HRQoL assessments at the time of EMA approval. After a monitoring period of at least three years, 24 updates were identified, resulting in 34 (31%) therapies where information on HRQoL was still not available. For the 76 therapies with reported information on HRQoL, cancer-specific instruments were mostly used (n = 49/76). Regarding cumulative evidence on median overall survival and HRQoL, 33 (n = 33/110, 30%) as well as 15 (n = 15/110, 14%) cancer drugs were lacking information on both study end-points at the time of approval and after monitoring, respectively. CONCLUSION: Our results demonstrate that there is an urgent need of routine re-evaluation of reimbursed cancer drugs with initially missing information on major outcomes. Standardisation of the typology and quality of HRQoL assessments need to be improved to allow better comparability of results.

The New FDA Real-World Evidence Program to Support Development of Drugs and Biologics.

FDA has launched a Real World Evidence (RWE) Program for using real-world evidence (RWE) to help support new indications for already approved drugs or biologics and postapproval studies. The plan also includes stakeholder engagement efforts, demonstration projects, leadership activities, and development of guidance documents to assist developers interested in using real-world data (RWD) to develop RWE to support FDA regulatory decisions. This plan was mandated by the Cures Act passed in 2016. Over the 24-month period from passage of the law until FDA officially announced their program, FDA has gone to considerable efforts to educate the public about the benefits of RWE and encourage researchers to consider situations where RWE trials can generate useful information. Through a variety of stakeholder engagement projects, including publication of articles in medical journals, participation in public meetings, and development of initiatives, FDA has put more effort into preparing the medical community for its new emphasis on RWE than any other new policy that I can recall.

Evolving Vision of Regulatory Science in the Global Medical Community.

"Regulatory science" (RS) has been defined in various ways, but, nevertheless, the definitions of RS in different parts of the world include many common elements. It seems to be a common view that RS is not basic or applied science but, rather, focuses on the estimation and prediction of safety and efficacy. Thus, we think RS overall should incorporate not only RS specifically for medical product assessment but also RS engineering to provide prediction and estimation tools for those purposes, including guideline/guidance development. It is important as well to consider the potential contribution of RS to rational medicine (i.e., to evidence-based medicine in a broader context), and especially to real-world evidence generation. We will look at how definitions of RS have evolved, and how we believe RS might develop in the future. Taking a patient-centric view, we re-emphasize RS is an ethical science contributing to society and human welfare.

Contrasting evidence to reimbursement reality for off-label use (OLU) of drug treatments in cancer care: rationale and design of the CEIT-OLU project.

Background: Off-label use (OLU) of a drug reflects a perceived unmet medical need, which is common in oncology. Cancer drugs are often highly expensive and their reimbursement is a challenge for many healthcare systems. OLU is frequently regulated by reimbursement restrictions. For evidence-based healthcare, treatment ought to be reimbursed if there is sufficient clinical evidence for treatment benefit independently of patient factors not related to the treatment indication. However, little is known about the reality of OLU reimbursement and its association with the underlying clinical evidence. Here, we aim to investigate the relationship of reimbursement decisions with the underlying clinical evidence. Methods/ design: We will extract patient characteristics and details on treatment and reimbursement of cancer drugs from over 3000 patients treated in three Swiss hospitals. We will systematically search for clinical trial evidence on benefits associated with OLU in the most common indications. We will describe the prevalence of OLU in Switzerland and its reimbursement in cancer care, and use multivariable logistic regression techniques to investigate the association of approval/rejection of a reimbursement requests to the evidence on treatment effects and to further factors, including type of drug, molecular predictive markers and the health insurer. Discussion: Our study will provide a systematic overview and assessment of OLU and its reimbursement reality in Switzerland. We may provide a better understanding of the access to cancer care that is regulated by health insurers and we hope to identify factors that determine the level of evidence-based cancer care in a highly diverse western healthcare system.

ISPOR, the FDA, and the Evolving Regulatory Science of Medical Device Products.

The International Society for Pharmacoeconomics and Outcomes Research (ISPOR) is a key venue for members from private industry, government, and academia to collaborate and share advances in regulatory, clinical, and reimbursement science for drugs, devices, and diagnostics. In parallel, the US Food and Drug Administration (FDA) "is responsible for advancing the public health by helping to speed innovations that make medical products more effective, safer, and more affordable." In 2012, the Medical Device Innovation Consortium (MDIC) was formed as a public-private partnership bringing together government, industry, and nonprofit organizations to advance approaches that promote patient access to safe, innovative medical technologies. With a focus on regulatory science, the MDIC has been assessing how to apply real-world evidence (RWE) regulatory science to medical devices. A key goal of this project is to review the history of RWE regulatory science, define terms, and explain why and how RWE is being considered across the total product life cycle, including regulatory assessment. Unique considerations of real-world data for in vitro diagnostics are also taken into account. We envision that these activities will help ensure a high level of rigor and integrity of RWE necessary for regulatory use cases and demonstrate where RWE can be successfully used for regulatory decision making. The ISPOR, FDA, and MDIC are providing the needed leadership in ensuring that diverse stakeholders share a meaningful voice in determining RWE use and, by so doing, are improving the quality and efficiency of care, enhancing health outcomes, and addressing broader societal concerns of reducing health disparities and costs.

Government policy interventions to reduce human antimicrobial use: A systematic review and evidence map.

BACKGROUND: Growing political attention to antimicrobial resistance (AMR) offers a rare opportunity for achieving meaningful action. Many governments have developed national AMR action plans, but most have not yet implemented policy interventions to reduce antimicrobial overuse. A systematic evidence map can support governments in making evidence-informed decisions about implementing programs to reduce AMR, by identifying, describing, and assessing the full range of evaluated government policy options to reduce antimicrobial use in humans. METHODS AND FINDINGS: Seven databases were searched from inception to January 28, 2019, (MEDLINE, CINAHL, EMBASE, PAIS Index, Cochrane Central Register of Controlled Trials, Web of Science, and PubMed). We identified studies that (1) clearly described a government policy intervention aimed at reducing human antimicrobial use, and (2) applied a quantitative design to measure the impact. We found 69 unique evaluations of government policy interventions carried out across 4 of the 6 WHO regions. These evaluations included randomized controlled trials (n = 4), non-randomized controlled trials (n = 3), controlled before-and-after designs (n = 7), interrupted time series designs (n = 25), uncontrolled before-and-after designs (n = 18), descriptive designs (n = 10), and cohort designs (n = 2). From these we identified 17 unique policy options for governments to reduce the human use of antimicrobials. Many studies evaluated public awareness campaigns (n = 17) and antimicrobial guidelines (n = 13); however, others offered different policy options such as professional regulation, restricted reimbursement, pay for performance, and prescription requirements. Identifying these policies can inform the development of future policies and evaluations in different contexts and health systems. Limitations of our study include the possible omission of unpublished initiatives, and that policies not evaluated with respect to antimicrobial use have not been captured in this review. CONCLUSIONS: To our knowledge this is the first study to provide policy makers with synthesized evidence on specific government policy interventions addressing AMR. In the future, governments should ensure that AMR policy interventions are evaluated using rigorous study designs and that study results are published. PROTOCOL REGISTRATION: PROSPERO CRD42017067514.

Model-Informed Drug Development: Current US Regulatory Practice and Future Considerations.

Model-informed drug development (MIDD) refers to the application of a wide range of quantitative models in drug development to facilitate the decision-making process. MIDD was formally recognized in Prescription Drug User Fee Act (PDUFA) VI. There have been many regulatory applications of MIDD to address a variety of drug development and regulatory questions. These applications can be broadly classified into four categories: dose optimization, supportive evidence for efficacy, clinical trial design, and informing policy. Case studies, literature papers, and published regulatory documents are reviewed in this article to highlight some common features of these applications in each category. In addition to the further development and investment in these established domains of application, new technology, and areas, such as more mechanistic models, neural network models, and real-world data/evidence, are gaining attention, and more submissions and experiences are being accumulated to expand the application of model-based analysis to a wider scope.

Perspectives on the opioid crisis from pain medicine clinicians.

Patients experiencing a terminal drug related event reflect a sentinel event. If this pharmacotherapy is a widely used agent, it may be viewed as a catastrophic problem. If patients are dying from illegal drug use when the medical establishment fails them by withdrawing or minimizing their medically prescribed medication, then the burden rests with their health care providers, legislation, and insurance carriers to actively participate in a collegial fashion to achieve parity. Causing a decay in functionality in previously functional patients, may occur with appropriately prescribed opioid medications addressing non-cancer pain when withdrawing or diminishing either with or without patient consent. The members of the medical profession have diminished their prescribing of opioids for their patients out of apparent fear of reprisal, state or federal government sanctions, and other concerned groups. Diminishing former dosages or deleting the opioid medication, preferably in concert with the patient, often results in inequitable patient care. Enforcing sanctioned decreases or ceasing to prescribe from their former required/established opioid medications precipitate patient discord. In absence of opioid misuse, abuse, diversion or addiction based upon medical "guidelines" and with a poor foundation of Evidence Based Medicine the CDC guidelines, it may be masked as a true guideline reflecting a decrement of clinical judgment, wisdom, and compassion. This article also discusses the role of pharmacy chains, insurance carriers, and their pharmacy benefit managers (PBMs) contribution to this multidimensional problem. There may be a potential solution, identified in this paper, if all the associated political, medical and insurance groups work cohesively to improve patient care. This article and the CDC guidelines are not focused at hospice, palliative, end of life care pain management.

Towards a supportive policy and commissioning environment for chemsex in England.

The use of drugs in sexual settings among gay men (colloquially referred to as 'chemsex') was first observed in services supporting gay men in London in the late 2000s. A decade on and it now features as a policy issue in the UK Government's latest Drug Strategy, with several actions to support a health system response. However, reaching this point has been a slow and challenging process and much remains to be done to facilitate an environment in which evidence-based chemsex interventions can be delivered. With a view to informing the development of policies and services in other contexts, this case report examines the initiatives that have driven a response to chemsex and contributed to policy development in England and highlights remaining challenges to effective service provision.

Balancing early access with uncertainties in evidence for drugs authorized by prospective case series - systematic review of reimbursement decisions.

AIMS: To review clinical and cost-effectiveness evidence underlying reimbursement decisions relating to drugs whose authorization mainly is based on evidence from prospective case series. METHODS: A systematic review of all new drugs evaluated in 2011-2016 within a health care profession-driven resource prioritization process, with a market approval based on prospective case series, and a reimbursement decision by the Swedish Dental and Pharmaceutical Benefits Agency (TLV). Public assessment reports from the European Medicines Agency, published pivotal studies, and TLV, Scottish Medicines Consortium and National Institute of Health and Care Excellence decisions and guidance documents were reviewed. RESULTS: Six drug cases were assessed (brentuximab vedotin, bosutinib, ponatinib, idelalisib, vismodegib, ceritinib). The validity of the pivotal studies was hampered by the use of surrogate primary outcomes and the absence of recruitment information. To quantify drug treatment effect sizes, the reimbursement agencies primarily used data from another source in indirect comparisons. TLV granted reimbursement in five cases, compared with five in five cases for Scottish Medicines Consortium and four in five cases for National Institute of Health and Care Excellence. Decision modifiers, contributing to granted reimbursement despite hugely uncertain cost-effectiveness ratios, were, for example, small population size, occasionally linked to budget impact, severity of disease, end of life and improved life expectancy. CONCLUSION: For drugs whose authorization is based on prospective case series, most applications for reimbursement within public health care are granted. The underlying evidence has limitations over and above the design per se, and decision modifiers are frequently referred to in the value-based pricing decision making.