Medical Products Industry Research Articles

A Proactive Response to Prescription Opioid Abuse

We at the Food and Drug Administration (FDA) continue to be deeply concerned about the growing epidemic of opioid abuse, addiction, and overdose — an epidemic directly related to the increasingly widespread misuse of powerful opioid pain medications. As the federal agency charged with ensuring that the drugs used by the U.S. public are both effective and safe, we are committed to working in partnership with other government agencies, health care providers, the medical products industry and, most important, patients and their families to deal proactively with this unfolding public health crisis, which has already profoundly affected individuals, families, and . . .

Microscopic Techniques for Sterility Assurance Support in the Medical Products Industry

Microscopic Techniques for Sterility Assurance Support in the Medical Products Industry

Industry Practices for Expedited Reporting to Investigators Conducting Research Under an IND.

Due to investigators' complaints about the volume and limited interpretability of expedited safety reports received in Investigational New Drug (IND) studies, the authors surveyed industry sponsors in late 2009 about their reporting practices. An Internet-enabled survey was submitted to 51 industry sponsors. Ten (20%) complete surveys were returned, 9 of which came from large pharmaceutical/biotechnology companies. Although the response rate in this study was low, considering the consolidation present in this sector, the preponderance of responses from large pharmaceutical companies provides a useful description of the safety reporting practices of a significant sector within the medical products industry. Sponsors described extensive safety-specialized resources for reporting individual events to the FDA and IND investigators. Aggregate reports, when prepared, were provided to the FDA but rarely to investigators. Sponsors reported receiving complaints from investigators about excessive volume and limited relevance of individual safety reports. These data suggest that investigators would likely benefit if industry sponsors decreased reporting of individual cases that are not readily interpretable and instead reported meaningful safety information from aggregate analyses.

After 20 years, industry critics bury skeptics, despite empirical vacuum.

After more than 20 years, the conflict of interest (COI) movement has failed to substantiate its central claim that interactions between physicians, researchers and the medical products industry cause physicians to make clinical decisions that are adverse to the best interests of their patients. The COI movement's instigators have produced no solid evidence of harm commensurate with their extravagant allegations. At the same time, they have diverted resources away from more worthwhile pursuits, such as basic and applied medical research, clinical care and medical education towards onerous compliance exercises and obtrusive laws. Perhaps worst of all, they have made it respectable to ignore the epistemological foundations of medical science, diverting attention away from the scientific merit of the information presented and focusing it instead on the identity and motives of those who present the information.

Same Song, Different Audience: Pharmaceutical Promotion Targeting Non-Physician Health Care Providers

Promotion of medical products by manufacturers to physicians in the US has been widespread for over a century [1], and in its traditional form includes strategies such as direct detailing visits (inperson product promotion by a pharmaceutical representative), sponsorship of Continuing Medical Education programs, gifts or other inducements, and free samples [2]. In the past two decades, numerous studies have shown that these interactions shape clinical knowledge and medication-prescribing behavior in ways that are not consistent with evidencebased practices [3,4]. As a result, some physicians and policymakers have sought to mitigate their influence. For example, many hospitals and academic medical centers have established policies that require disclosure of certain behaviors that create conflicts of interest—like service on a manufacturer’s speaker’s bureau—or limit excessive non-research consulting payments that physicians may receive [5– 7]. These local efforts have now been supplemented in the US by the Centers for Medicare and Medicaid Services’ Open Payments program (created by the Physician Payments Sunshine Act) [8], which began receiving comprehensive information from drug and medical device manufacturers in August 2013 about all payments made to physicians and hospitals and plans to publicly disseminate the data starting in 2014. With greater regulatory attention to traditional promotional practices, ‘‘nontraditional’’ forms of promotion remain an option for pharmaceutical and medical device companies. Non-traditional promotion can include scientific pursuits or other business relationships that might appear to be outside the realm of promotion but that are conducted for a marketing purpose, such as seeding trials or funding of patient advocacy organizations [9,10]. It also includes targeting promotion to non-physician health care providers, such as nurse practitioners, pharmacists, and physician assistants. With recent changes in health care financing, these non-physician providers are taking an increasingly central role in care delivery, as medicine emphasizes interdisciplinary team-based care and integrative medical homes [11]. Thus, these providers offer a high-impact marketing alternative to traditional physiciandirected promotion [12]. Grundy and colleagues, in this week’s issue of PLOS Medicine, provide a systematic review of literature addressing the nature of non-physician providers’ interactions with the medical products industry [13]. The authors identified fifteen studies published between 2003 and 2010 that investigated the type and frequency of interactions, non-physician providers’ attitudes towards industry interactions, and the perceived effect of industry influence. The majority of the studies (11 out of 15) were conducted in the US, with participant size ranging from 14 to 1,640. One conclusion of their review was that nearly all of the US-based nurse practitioners responding in the studies have regular pharmaceutical representative contact (96%), have received industry-sponsored meals within the past 6 months (64%), have attended an educational event during the past five years paid for by the industry (96%), and have received free drug samples (66–86%). The pervasive contact between nonphysician providers and the medical products industry recalls a survey by Campbell and colleagues in 2004 that found 94% of physicians reporting recent interactions with pharmaceutical industry sales representatives [14]. Notably, a follow-up survey in 2009 found somewhat fewer physicians (84%) reporting such interactions, while a review of Massachusetts data from 2011 and 2012 suggests that only approximately one in four physicians received high-value monetary gifts (.$50) [15,16]. Though these are not longitudinal data, they suggest that recent policy changes have been successful in insulating Linked Research Article

Rapid Prototyping in Developing Process with CA Systems Application

Rapid Prototyping (RP) presents the automatic production of physical parts using by additive manufacturing technology. The start techniques for Rapid Prototyping became available in the late 1980s and were used to produce models and prototype parts. Today they are used for a much wider range of applications and are even used to manufacture production-quality parts in relatively small numbers. Rapid Prototyping is widely used in the automotive, aerospace, medical, and consumer products industries. In paper is presented process of design product development, product production and testing of products produced by Fused Deposition Modelling rapid prototyping technology.

Effects of alginate oligosaccharide mixtures on the growth and fatty acid composition of the green alga Chlamydomonas reinhardtii

Alginate is a natural acidic linear polysaccharide that is produced by brown seaweeds. It is currently used in a broad range of commercial enterprises, such as the food and medical products industries. Recent evidence has demonstrated that alginate oligosaccharides may function as growth promoting agents for certain plant cells, including those of some green algae. Chlamydomonas reinhardtii is a green alga that is used as a model organism in fundamental molecular biology studies; it is also a producer of biohydrogen. In the present study, we examined effects of two types of alginate oligosaccharide mixtures (AOMs), which were prepared by either enzymatic degradation (ED) or acid hydrolysis (AH), on the growth of C. reinhardtii. Growth was significantly promoted by AOM (ED) in a concentration-dependent manner. The maximum effect was observed on day 4 of treatment. The fatty acid composition of C. reinhardtii was also influenced by AOM (ED); the levels of C16:0, C18:2 cis and C18:3 n-3 increased in treated cells. AOM (AH) and the other saccharides that we tested did not affect the growth of C. reinhardtii. The effects that we identified could promote efficient biomass production by reducing culture times and by changing cellular fatty acid levels.

Time to 'walk the walk' about industry ties to enhance health

Overwhelming evidence that relationships between universities, physicians and the medical products industry benefit patients explains the ubiquitous calls to encourage such relationships. Yet accumulating 'conflict of interest' regulations in academic health centers, government and industry have had the opposite effect. Justifications underlying the regulations lack quantitative rigor, and the rules they enforce impose costly bureaucratic requirements of dubious benefit. Evidence shows that they have diminished the collaborations deemed beneficial to health enhancement.

A Historical Perspective on Clinical Trials Innovation and Leadership

THE RANDOMIZED CONTROLLED TRIAL (RCT), THE GOLD standard for evaluating the balance of risk and benefit in medical therapies, first emerged as a key clinical research tool in the mid-20th century thanks to visionary leadership of agencies such as the US National Institutes of Health (NIH), the UK Medical Research Council, and academic research institutions. Since then, clinical trials activity has shifted from the NIH and academia into the purviews of the medical products industry and regulatory authorities. Recent emphasis on evidence-based medicine, patient-centered outcomes research, and learning and accountable health care systems underscores the fact that most clinical trials fail to provide the evidence needed to inform medical decision making. However, the serious implications of this deficit are largely absent from public discourse, and a better balance between commercial interests and public health is critically needed. In this context, the word “academic” describes a diverse group of individuals exploring scholarly questions, with motivations arising not from pursuit of profit but from an interest in the public health. The wellsprings of such activity should reside in the NIH and other federal research agencies, coupled with external grantees—most of whom work in the nation’s academic health and science systems. The primary mission of academic health and science systems, as required by their not-for-profit status, places public health interests above return on investment to specific investors. This in no way disparages the motivations of the many excellent scientists working in industry or in the US Food and Drug Administration (FDA) that regulates its products. On the contrary, the development and appropriate use of medical technologies are vital to the public health. However, it is important to remain mindful that decisions affecting forprofit research will reflect fundamentally different priorities than those of academic researchers. In a sense, the academic enterprise seeks a “return on investment” for taxpayers who grant (and support) its nonprofit status. Thus, while all researchers are bound by the same standards when conducting human studies, the fundamental questions addressed will differ, and failure on the part of academia to increase its involvement will have predictable consequences. When fundamental trials methodologies were being developed at the NIH in the 1960s, an NIH-commissioned task force delineated recommendations for organizing and conducting RCTs. One significant early example is the Coronary Drug Project, a joint effort among NIH sponsors, an academic coordinating center, and a steering committee of academic leaders. In the 1970s and 1980s, the NIH often convened academic leaders to identify knowledge gaps and prioritize and conduct specific trials as funding permitted. During the 1960s, there was scant statistical literature examining clinical trials methodologies. Researchers learned by doing trials, noting successes and failures, and iterating to advance the field. In a series of discussions in the 1970s, ideas were debated and solutions to immediate problems were proposed. Throughout the 1970s and 1980s, NIH and academic biostatisticians developed many methods now in routine use, including sample size estimation, interim data monitoring, and repeated measure methods for analysis. At the outset of this era, few large randomized clinical outcomes trials were sponsored or conducted by industry. Meanwhile, the FDA was developing biostatistical teams to support review of new drug and device applications and increasingly demanded RCTs, often with clinical outcomes end points, as the standard for approval and labeling. By the early 1990s, academia was working with industry to lead and conduct clinical trials, using a modification of the NIH organizational structure. While some fields developed this hybrid model of academic leadership in industry-sponsored RCTs, most industry trials evolved in a different direction and were designed by industry scientists in concert with regulators, often with little or no independent academic input. As the clinical trials enterprise grew, statistical principles mandated adequate sample sizes to provide power for detecting typically modest differences in clinical outcomes. Concurrently, the enterprise’s rapid expansion, coupled with egregious instances of fraud or lapses in quality, resulted in the implementation of auditable data systems. This confluence of factors spurred massive increases in clinical trial costs.

There Is a Role for Industry-Sponsored Education in Cardiology

Education: “The process or art of imparting knowledge, skill and judgment; Facts, skills and ideas that have been learnt, either formally or informally.” — Wikipedia 1 The term profession is applied to those persons who have specialized and technical skill or knowledge which they apply, for a fee, to certain tasks that ordinary and unqualified people cannot ordinarily undertake. The term derives from the Latin: “to swear (an oath) …” . — Wikipedia 2 Let’s consider how we as cardiovascular medicine specialists spend our days in the care of people with cardiovascular disease. In the office or making rounds in the hospital, we prescribe drugs and order diagnostic tests; in the noninvasive laboratory, we obtain and interpret images of the heart; in the electrophysiology and cardiac catheterization laboratories, we program and implant devices in patients. When antithrombotic and fibrinolytic drugs are administered, and primary percutaneous coronary intervention is done using balloon catheters and intracoronary stents, lives are saved among patients with acute myocardial infarction. Response by Avorn and Choudhry see p 2221 The mortality risk from heart failure decreases and quality of life increases from the proper and appropriate use of angiotensin-converting enzyme inhibitors and β-blockers. Lipid lowering through the use of statin drugs saves lives and reduces serious cardiovascular complications such as myocardial infarction and stroke when properly prescribed to patients with a variety of manifestations of atherosclerotic vascular diseases. According to a recent publication by Ford and colleagues,3 deaths due to coronary heart disease in the United States declined substantially from 1980 to 2000, resulting in >340 000 fewer deaths in 2000. The authors attributed approximately half of this decline to changes in cardiac risk factors and half to the application of evidence-based therapies. An underlying theme in all of this is that the pharmaceutical, biotechnology, and …

Integrating Medical Science Liaisons into Key Account Management

Medical Science Liaison (MSL) teams are a well-recognized function within the pharmaceutical and medical products industries. While in most organizations, MSLs have focused on the development of relationships with individual Key Opinion Leaders, progressive companies have realized the value that MSLs can also bring to Key Account Management (KAM). This article discusses the five steps that should be followed in order to successfully integrate the support of Key Accounts into an MSL function. These include understanding the business approach to KAM, identifying what MSL resources are available, developing a comprehensive strategic plan, implementing the plan, and evaluating and making any necessary adjustments. Finally, a case example outlining the experience of a small pharmaceutical company, and how the MSL function supported KAM will be shared.

JSPS Asia and Africa Scientific Platform Program Development for the Medicinal Chemistry Based on Biologically Active Natural Products in the Subtropical Zone

In 2005, the independent administrative institution the "Japan Society for the Promotion of Sciences (JSPS)" initiated the "Asia and Africa Science Platform Program", which is a new project aimed to create high potential research hubs in selected fields within the Asian and African region, while fostering the next generation of leading researchers. Another goal is to establish sustainable collaborative relationships among universities and research institutes in Japan and other Asian and African countries. In this project, we consider natural sources existing in partner countries to be the most important factor in the production of medicine. We will search for target compounds and analyze their structures by screening biologically active natural products. Additionally, we will design functional molecules and create process for retrieving a large supply of target compounds based on a bioprospecting strategy. Thailand, Indonesia, and India share the vision of enhancing collaborative efforts. By conducting this researche, we will focus on academic research that is necessary for the development of the pharmaceutical and medical products industry in partner countries. There are four selected research topics as followeds: 1) Development of New Antitumor Agents based on Marine Natural Products; 2) Development of New Anticoagulants and Anti-VEGF; 3) Molecular Epidemiological Investigation of Emerging Infectious Diseases and Development of Novel Diagnosis and Therapeutic Agents; and 4) Medicinal Chemistry on Biologically Active Natural Products from the Traditional Condiments and Medicines. The exchanges might take the form of joint research seminars. The first Medicinal Chemistry Seminar of the AA Scientific Platform Program was co-organized with the 23th Annual Research Conference on Pharmaceutical Sciences, Thailand at Chulalongkorn University, Bangkok, on December 14-15, 2006. The 2nd JSPS seminar was co-organized with the 1st Bioactive Natural Products from Marine Organisms and Endophytic Fungi (BNPME) seminar and held in Phuket, Thailand between October 25-28, 2007. The JSPS 3rd Medicinal Chemistry Seminar of the Asia/Africa Scientific Platform Program was co-organized with The 2nd International Seminar of MPU-AACDD in Tokyo on January 14-15, 2009.

A Virtuous Cycle to Improve Hypertension Outcomes at a National Level

Compared with the seemingly orderly approach to science associated with controlled laboratory environments, the assessment of broad changes in clinical practices and their impact on society is maddeningly complex and difficult to ascertain with confidence. Yet, in the end, the favorable regard of most societies toward public funding of biomedical science hinges on the belief that the end product of such research will benefit human health. This critical societal trust has been eroded by a growing skepticism directed toward the biomedical research enterprise and its associated industries, particularly the pharmaceutical industry. In this issue of Hypertension , Campbell et al1 report on their analysis of the impact of a program to improve the treatment of hypertension across Canada, one that has corresponded with increased use of antihypertensive medications and reduced incidence of death, stroke, myocardial infarction, and heart failure. The authors took advantage of the confluence of a major change in guideline recommendations, concerted national efforts linking professional societies and public health to control hypertension, and excellent sources of public data. These data allowed them to track prescriptions written by Canadian physicians and to correlate them with rates of key events (death and major cardiovascular and neurologic events) in the overall population. Using the powerful statistical technique of time series analysis, they demonstrated that rates of these critical events declined in direct proportion to the increase in prescription of antihypertensive medications, beginning in 1999. Taken at face value, this study provides compelling evidence that broad changes in medical care, when supported by convincing evidence from clinical trials, can result in improvements in death and disability for populations at the national level. Skeptics will …

Biphasic Effects of Postnatal Exposure to Diethylhexylphthalate on the Timing of Puberty in Male Rats

Phthalate esters such as di(2-ethylhexyl)phthalate (DEHP), which are commonly found in cosmetics and in flexible plastics distributed by the food, construction, and medical products industries, have been classified as anti-androgens. High-dose DEHP exposure in utero is associated with decreased androgen levels. However, when administered after birth, low doses of DEHP (eg, 10 mg/kg body weight) may stimulate androgen production. In the present study, the potential of phthalate exposure to advance or delay the timing of puberty was assessed. Male Long-Evans rat pups were chronically subjected to low or high doses of DEHP, with the androgen-driven process of preputial separation serving as an index of pubertal timing. Rats were treated with 0, 10, 500, or 750 mg/kg body weight DEHP for 28 days starting at day 21 postpartum. The average age at which the animals completed preputial separation was measured in each group. The age of preputial separation was 41.5 +/- 0.1 days postpartum in controls (vehicle). The 10 mg/kg DEHP dose advanced pubertal onset significantly to 39.7 +/- 0.1 days postpartum, whereas the 750 mg/kg DEHP dose delayed pubertal onset to 46.3 +/- 0.1 days postpartum. The 10 mg/kg DEHP dose also significantly increased serum testosterone (T) levels (3.13 +/- 0.37 ng/mL) and seminal vesicle weights (0.33 +/- 0.02 g) compared with control serum T (1.98 +/- 0.20 ng/mL) and seminal vesicle weight (0.26 +/- 0.02 g), while the 750 mg/kg dose decreased serum T (1.18 +/- 0.18 ng/mL) as well as testes and body weights. Direct action of the DEHP metabolite, monoethylhexylphthalate (MEHP), on Leydig cell steroidogenic capacity was investigated in vitro. MEHP treatment at a low concentration (100 microM) increased luteinizing hormone-stimulated T production, whereas 10 mM concentrations were inhibitory. In conclusion, data from the present study indicate that DEHP has a biphasic effect on Leydig cell function, with low-dose exposure advancing the onset of puberty. High doses of DEHP, which are anti-androgenic, may also be outside the range of real environmental exposure levels.

New product introduction at TyRx Pharma, Inc.

Purpose – To describe a practice that has implications for new product introduction within and outside the medical products industry. Design/methodology/approach – The case describes a systems approach to new product introduction that includes a number of non‐marketing factors. The organization's original name has been retained. One of the authors is an executive with the company and used both internal and publicly available data to write the case study. Findings – The case provides information and a solid action approach to new product launch. The subject company designed a comprehensive launch strategy that involved new product modification as well as selection of appropriate price and distribution strategies. The results offer direct implications for new product development teams in the drug and medical implements industries. Research limitations/implications – As in all case studies, the specific conditions found in one organization may not be found more generally in others. Readers are cautioned that the conclusions drawn in the case may have limited applicability. Practical implications – The case depicts a professional implementation of a new product launch. Other organizations may find the technique of value in their own efforts. Originality/value – The case is a unique implementation of a new product launch strategy that has a comprehensive foundation. It offers lessons that may be applied to other companies faced with similarly competitive, regulatory and technological environments.

Spores of Bacillus subtilis: their resistance to and killing by radiation, heat and chemicals

A number of mechanisms are responsible for the resistance of spores of Bacillus species to heat, radiation and chemicals and for spore killing by these agents. Spore resistance to wet heat is determined largely by the water content of spore core, which is much lower than that in the growing cell protoplast. A lower core water content generally gives more wet heat-resistant spores. The level and type of spore core mineral ions and the intrinsic stability of total spore proteins also play a role in spore wet heat resistance, and the saturation of spore DNA with alpha/beta-type small, acid-soluble spore proteins (SASP) protects DNA against wet heat damage. However, how wet heat kills spores is not clear, although it is not through DNA damage. The alpha/beta-type SASP are also important in spore resistance to dry heat, as is DNA repair in spore outgrowth, as Bacillus subtilis spores are killed by dry heat via DNA damage. Both UV and gamma-radiation also kill spores via DNA damage. The mechanism of spore resistance to gamma-radiation is not well understood, although the alpha/beta-type SASP are not involved. In contrast, spore UV resistance is due largely to an alteration in spore DNA photochemistry caused by the binding of alpha/beta-type SASP to the DNA, and to a lesser extent to the photosensitizing action of the spore core's large pool of dipicolinic acid. UV irradiation of spores at 254 nm does not generate the cyclobutane dimers (CPDs) and (6-4)-photoproducts (64PPs) formed between adjacent pyrimidines in growing cells, but rather a thymidyl-thymidine adduct termed spore photoproduct (SP). While SP is formed in spores with approximately the same quantum efficiency as that for generation of CPDs and 64PPs in growing cells, SP is repaired rapidly and efficiently in spore outgrowth by a number of repair systems, at least one of which is specific for SP. Some chemicals (e.g. nitrous acid, formaldehyde) again kill spores by DNA damage, while others, in particular oxidizing agents, appear to damage the spore's inner membrane so that this membrane ruptures upon spore germination and outgrowth. There are also other agents such as glutaraldehyde for which the mechanism of spore killing is unclear. Factors important in spore chemical resistance vary with the chemical, but include: (i) the spore coat proteins that likely react with and detoxify chemical agents; (ii) the relative impermeability of the spore's inner membrane that restricts access of exogenous chemicals to the spore core; (iii) the protection of spore DNA by its saturation with alpha/beta-type SASP; and (iv) DNA repair for agents that kill spores via DNA damage. Given the importance of the killing of spores of Bacillus species in the food and medical products industry, a deeper understanding of the mechanisms of spore resistance and killing may lead to improved methods for spore destruction.

The importance of news media in pharmaceutical risk communication: proceedings of a workshop

In response to mass media's role in the national and global system of pharmaceutical risk communication, the Centers for Education and Research on Therapeutics (CERTs) convened a 'think tank' session on the 'Importance of Media in Pharmaceutical Risk Communication'. Prominent journalists and experts from the pharmaceutical industry, academia, medical practice and government were invited to consider the benefits and challenges of improving the way we communicate the benefits and risks of therapeutics via mass media, especially news media. Workshop discussions revealed a paucity of systematic research directed towards understanding how and why news media report on therapeutic risk, the impact of this coverage and how coverage can be improved. Consequently, participants produced a research agenda capturing the key aspects of the flow of information around this topic, including the meaning of risk, how news audiences process and use therapeutic risk information in the news, how and why news organizations report on therapeutic risk, and the role and impact of the pharmaceutical industry, government officials and academic researchers as sources of therapeutic risk information. The workshop ended with a discussion on action items addressing what news professionals, representatives of regulatory agencies and the medical products industry, and academic researchers can and should do to enable news media to effectively report therapeutic risk information. In sum, this proceedings report provides an outline for developing mass media risk communication research, influencing the practices of journalists and expert sources and ultimately, improving the quality of the public's life.

In-sourcing as a Strategy for Reclaiming Union Work

Drawing on examples from the automobile and medical products industries, this paper outlines an approach for confronting outsourcing. Two dimensions define the approach. The first in volves a direct challenge to the costing method used by manage ment in make-or-buy decisions; for various reasons, management often employs a flawed comparison method that unfairly burdens in-house operations. The second dimension involves a shop-level process for systematically collecting data on the full range of costs associated with outsourcing, and then incorporating such costs into the make-or-buy comparison. This paper concludes that the present economic conditions of diminished capacity utilization and layoffs present an opportunity for unions to in-source work and reemploy union members.

Conflict of interest

The clinical research enterprise is increasingly scrutinized, in part because of the issue of conflict of interest. The issue is broad and its implications touch on a wide range of concerns, from the safety of patient care to the viability of a large industry. Numerous constituencies are affected by conflict of interest, and representatives of all of them convened in November 2002 for a one-and-a-half day discussion of the issues as well as possible solutions to both the perception and the actuality of such conflict. Participants included medical journal editors, news reporters, physician investigators, representatives of institutional conflict-of-interest oversight committees, representatives of the medical products industry, and Federal regulators. The resulting manuscript provides a review of the issues as well as desirable ways for each of the players to monitor themselves; each section thus contains provocative recommendations for eliminating conflict of interest to ensure that our vibrant health care system continues to foster exciting new advances to improve patient care.

Practical clinical trials: increasing the value of clinical research for decision making in clinical and health policy.

Decision makers in health care are increasingly interested in using high-quality scientific evidence to support clinical and health policy choices; however, the quality of available scientific evidence is often found to be inadequate. Reliable evidence is essential to improve health care quality and to support efficient use of limited resources. The widespread gaps in evidence-based knowledge suggest that systematic flaws exist in the production of scientific evidence, in part because there is no consistent effort to conduct clinical trials designed to meet the needs of decision makers. Clinical trials for which the hypothesis and study design are developed specifically to answer the questions faced by decision makers are called pragmatic or practical clinical trials (PCTs). The characteristic features of PCTs are that they (1) select clinically relevant alternative interventions to compare, (2) include a diverse population of study participants, (3) recruit participants from heterogeneous practice settings, and (4) collect data on a broad range of health outcomes. The supply of PCTs is limited primarily because the major funders of clinical research, the National Institutes of Health and the medical products industry, do not focus on supporting such trials. Increasing the supply of PCTs will depend on the development of a mechanism to establish priorities for these studies, significant expansion of an infrastructure to conduct clinical research within the health care delivery system, more reliance on high-quality evidence by health care decision makers, and a substantial increase in public and private funding for these studies. For these changes to occur, clinical and health policy decision makers will need to become more involved in all aspects of clinical research, including priority setting, infrastructure development, and funding.