Corporations and Campus Research: How private industry dollars influence scientific discovery and threaten public health

Posted on by Corporations and Health Watch

On March 26, 2008, the New York Times published a front page story revealing that the Liggett Group, a major tobacco company, had supported research at Weill Cornell Medical College showing the benefits of early screening for lung cancer. The article, published by the New England Journal of Medicine in 2006 did not disclose the source of funding. The Journal’s editor, Dr. Jeffrey M. Drazen, told the Times, “In the seven years that I’ve been here, we have never knowingly published anything supported by a cigarette maker.” The authors of the report and officials at Weill Medical College denied any effort to cover up the source of the funding. However, former New England Journal editor Dr. Jerome Kassirer, author of a book about medical conflicts of interest, expressed skepticism about this denial. He told the Times that he believed that Weill Cornell had created the foundation to hide its receipt of money from a cigarette company. You have to ask yourself the question, ‘Why did the tobacco company want to support her research?’ They want to show that lung cancer is not so bad as everybody thinks because screening can save people; and that’s outrageous.

Last November, the University of California at Berkeley and BP, the global energy company formerly known as British Petroleum, signed a $500 million, 10-year deal to create the Energy Biosciences Institute to conduct research on energy and environmental issues. BP will appoint four of the Institute’s eight directors and, according to the Daily Cal, the Berkeley student newspaper, at least 50 BP scientists will be able to conduct proprietaryresearch at UC Berkeley and the University of Illinois. These researchers work under the sole control and discretion of BP, and their work can remain secret and thus free from scrutiny. Critics expressed concerns about the academic integrity of the Institute and also questioned a partnership with a company that has been indicted in numerous environmental violations and illegal business practices. Only a few months prior to signing the contract with Berkeley, BP and its subsidiaries paid $373 million to settle dozens of legal cases, including one that involved the leaking of crude oil from pipelines in Alaska.

To prove that UC doesn’t limit sponsorship to industries under attack by public health and environmental advocates, University of California at Davis recently accepted an endowed chair in chocolate science from the Mars Corporation in order to study the antioxidant properties of cacao.In fiscal year 2006-7, UC received more than $16.6 million from Philip Morris for tobacco research, and in September 2007, the Board of Regents voted 14 to 4 to continue accepting tobacco money for faculty research. According to the San Francisco Chronicle, nearly all the regents expressed disdain for the tobacco industry’s criminal behavior and distortion of research, but several of those who voted to continue to accept funding said they were deferring to faculty concerns about academic freedom. Intended to shield researchers from tobacco industry influences, the resolution adds new administrative procedures. Under this new measure, research proposals seeking tobacco industry funding are now required to pass through a scholarly review and receive approval from the campus chancellor. In addition, the UC president must present annual reports to the Regents on the number of proposals submitted, approved and funded, along with a description of each.

Moving east, the University of Virginia’s School of Medicine decided in 2006 to accept $25 million from Philip Morris to fund research on youth and tobacco. When challenged on the decision, Dean Arthur Garson insisted the answer was simple, a company has offered us $20 million to develop better ways so kids don’t smoke. Period.

These and many similar accounts highlight a growing trend in academia to accept industry money to pay for research, new laboratories, and high-powered professors. In 2005, industry provided universities with $2.3 billion for research and development. While the dollar amount has been growing, according to Daniel Greenberg, author of Science for Sale The Perils, Rewards and Delusions of Campus Capitalism,1 industry actually contributes only a tiny fraction of the overall university research budget—far more comes form government sources such as the National Institutes of Health (NIH) and the National Science Foundation (NSF). In New York State, for example, total university spending on research and development in 2004 was $3.4 billion, of which only $146 million—just over 4%—came from industry.

Why the new push for corporate funding for university research?

If industry pays for only a small part of academic research, why are universities now so eager to pull in industry dollars? Why are they willing to cede control of their own research, a prerogative often jealously guarded in the past? And what are the consequences of this growing source of support for academic institutions and for public health research? In this reportCorporations and Health Watch examines industry influence on academic research; assesses its impact on universities, science and public health; and describes critics’ efforts to counter this trend and pose other policy options.

As in any intimate relationship, changes reflect the concerns of both partners. For universities, the most obvious starting point is dollars. Between 1970 and 2003, federal funding for research increased dramatically, making it easy for many universities and researchers to steadily increase their research revenues. Just between 1999 and 2003, the NIH budget more than doubled from $13 billion to $27 billion.2 But since then, the Bush Administration has cut funding for scientific research at both NIH and NSF, forcing universities to turn elsewhere to support their habit.

On the business side, the quest for a stronger and more direct presence in university research reflects the downturn in federal funding but also a recognition that direct funding offers some advantages. These include the right to conduct research that benefits companies directly; to withhold information that could jeopardize profits; and to send university scientists to appear in public forums to advance the company’s agenda, perhaps with greater credibility than their own staff. In the longer run, these trends can help business to privatize university research, allowing market forces and the search for profits—rather than academic traditions—to dictate the rules of research. As Robert Reich notes in his new book Supercapitalism,3 increased competition among global companies forces them to seek every competitive edge they can find. Increasingly, bought scientists are one such edge.Rather than discontinue research projects altogether, universities and health institutions are taking up partnerships with corporations, exchanging rights to intellectual property for financial support. While this practice is not uncommon to university engineering and technology programs, its increasing presence in the biomedical and other health sectors is of particular concern to the health of the public.

The BP deal with Berkeley illustrates these benefits of direct funding, allowing dozens of scientists to pursue a research agenda shaped by the company on university property, where scientists benefit from the publicly supported (through California tax support and prior NIH funding) research infrastructure but escape the usual obligation to share their findings with the public and the wider scientific community.

The tobacco industry has long hired scientists to ‘debunk,’ or increase doubt about accepted scientific findings that show that tobacco causes cancer and other health conditions. Research studies show that several industries often withhold research findings that could cause a problem for their products or choose to require scientists to pose their research questions in a way that minimizes the possibility for finding harm.

In 2005, the British newspaper The Observer reported that a respected osteoporosis researcher at Sheffield University had questioned American pharmaceutical giant Procter and Gamble’s (P&G), decision to publish drug research in his name even though he had not been given full access to the data that the paper reported, and that the report was written by a ‘ghost writer’ paid for by P&G before being given to him.When researchers change findings at the behest of the sponsoring company to or fail to disclose industry sponsorship of their work, companies exploit the credibility of apparently independent scientists. In the case of Vioxx, the painkiller withdrawn from the market by Merck after it was linked to serious cardiovascular side effects, it appears that university scientists changed their findings at the behest of the company. The editor of the New England Journal of Medicine, which originally published the study, charged that an internal company memo showed that the researchers knowingly suppressed data on three additional heart attacks among Vioxx users that was available months before the paper was published.4 Had that data been included, Vioxx would have looked much riskier.

If universities and companies benefit from new partnerships, what’s the problem?

While growing corporate academic research partnerships may bring benefits to both universities and companies, they raise serious problems for academic integrity, scientific credibility and public health.

First, the imperative to produce findings that benefit the bottom line encourages biased, even dangerous science. For example, on his blog (BrodyHooked) and in his new book Hooked: How Medicine’s Dependence on the Pharmaceutical Industry Undermines Professional Ethics,5 Howard Brody, Director of the Institute for the Medical Humanities University of Texas Medical Branch notes that commercially sponsored studies paid for by the pharmaceutical industry are roughly four times more likely than neutral studies to favor the company’s drug. So commercial bias has been shown to be real and substantial.Similarly, researchers found that studies sponsored by the food industry to evaluate the health benefits of their product were 7.6 times more likely to find such benefits than were studies wholly funded by independent sources.6

Closer corporate ties may also jeopardize traditional academic values of freedom of inquiry, an obligation to share and disseminate research findings freely, and to criticize other researchers’ work without fear of reprisal. In exchange for their dollars, companies often ask universities to sign agreements that restrict publication rights, assign patents or other intellectual property to the company rather than the scientist or the public, and compromise protections for human volunteers.This biased evidence base can skew public policy deliberations—if negative findings have been suppressed, policy makers may falsely assume a product has been demonstrated to be safe. Moreover, increased media focus on industry manipulation of scientific research to benefit its bottom line, whether by suppressing negative findings, ghost writing articles, or preventing authors from sharing proprietary discoveries that could benefit the sponsoring company, can tarnish all scientists. This increased distrust of scientists can make it harder for researchers to participate in public debate as independent voices. For example, when it turned out that much of the research evidence—and advocacy—on behalf of the Human Papilloma Virus vaccine was sponsored by Merck & Co., the maker of the vaccine Gardasil, many citizen groups opposed mandatory vaccinations, even though most public health officials believe the vaccine is a public health advance.7

Since companies support research that they believe will bring in new revenues, they are more likely to fund projects that yield intellectual property that can be patented and sold, such as alternative fuel sources, new processed foods, or medical drugs and devices. Some of these products may promote population health but others do not. Significantly, research that benefits the public but does not generate profits is avoided, thus skewing the research enterprise. As corporate funding increases and government funding declines, this trend may accelerate.

Companies often attach many strings to their gifts, ensuring they can maintain control of the research. For example, in the partnership between BP and UC Berkeley, BP requires that it appoint company representatives for 4 out of 8 board of director seats. Corporate ties to university leaders are especially prevalent in medical schools. In a national survey of department chairs at 140 medical schools and teaching hospitals, Eric Campbell, Senior Scientist at the Institute for Health Policy at Massachusetts General Hospital, found that 60% of department chairs and 67% of departments as administrative units had relationships with industry—as a consultant, member of an advisory board, paid speaker, officer, founder, or member of the board of directors.8 When such ties are normative, resisting undue corporate influence may be especially difficult.

Developing guidelines for reducing corporate influence on university research

In summary, closer ties with corporations may represent a threat to universities because they can undermine academic freedom, divert university resources from other more pressing scientific questions and social needs, and make universities accessories to corporate interests rather than free-standing critical institutions.

In recent years, several research organizations and researchers have proposed guidelines to reduce corporate influences on university research. Many professional organizations, university administrators and researchers are resisting the corporate takeover and seeking to establish professional guidelines and standards that limit corporate influence on the university.

Public Citizen’s Health Research Group, for example, lays out a framework in which one can begin to think about solutions to or prevention of potential conflicts. In a 2007 report to the Institute of Medicine’s Committee on Conflict of Interest in Medical Research, Education, and Practice, the Health Research Group described three basic approaches that can be taken up by institutions—legal restrictions, policy restrictions, and disclosure.9

As an example of a policy decision, the University of Texas’ McCombs School of Business recently turned down an offer of money from Altria Group, the former parent company to Philip Morris. For UT McCombs, the decision was an ethical one. Dean George stated the leadership of the school felt that in some sense it was tainted money, that it is money gotten from a product that is significantly harming people. Associate Dean Paula Murray called the decision to turn down Altria’s money a no-brainer. 10

Professional associations like the International Epidemiology Association, the Institute on Medicine as a Profession, and the Union of Concerned Scientists, as well as advocacy campaigns such as the Restoring Scientific Integrity Network, the Prescription Project, theCenter for Tobacco Control Research and Education, and the Center for Science in the Public Interest work to educate researchers about corporate influences on university research and advocate for the adoption of policies that will remove industry interests from academic research endeavors.

Both the Center for Science in the Public Interest (CSPI) and the Union of Concerned Scientists offer explicit policy options for universities and individual researchers.

 

How to get corporate interests out of academic research

1. Universities can adopt corporate funding policies to protect their autonomy and preserve researchers’ academic freedoms.

2. Universities can prohibit representatives of corporate donors from sitting on research programs’ governing boards.

3. Universities can prohibit industry donors from controlling the content and direction of research programs.

4. Universities can eliminate ‘first rights’ intellectual property clauses from donor agreements.

5. Universities can ensure that company representatives cannot make substantive editorial changes in manuscripts or delay their publication.

Source: The Center for Science in the Public Interest. Strings Tied to Industry-Academic Collaborations at ‘Big Oil U.’ Press Release. Jan 22, 2008.

And the Union of Concerned Scientists called on the scientific community to hold Congress accountable to upholding the pursuit of scientific integrity with the following suggestions:

Scientists employed by government institutions commit themselves to serve the public good free from undisclosed conflicts of interest and to carry out science that is reliable and useful, while respecting statutory limitations such as national security laws. Therefore, government scientists should, without fear of reprisal or retaliation, have the freedom to:

  • Conduct their work without political or private-sector interference;
  • Communicate candidly their findings to Congress, the public, and their scientific peers;
  • Publish their work and to participate fully in the scientific community;
  • Disclose misrepresentation, censorship, and other abuses of science; and
  • Have their technical work evaluated by scientific peers.

A third set of guidelines, shown below, has been proposed by the Royal Netherlands Academy of Sciences.11 These provide detailed suggestions for how to negotiate university industry agreements that do not compromise academic integrity or bias results. By using these various guidelines, academic institutions and university researchers can begin to reassert their rights and responsibilities to set the terms for their scientific inquiries.

Declaration of scientific independence*

1. The structure of the research shall not be geared towards producing the desired outcome for the client.

2. The assignment and its objective shall preferably be formulated jointly by the client and the researcher.

3. Remuneration and other tokens of appreciation shall never depend on the outcomes or interpretation of the research.

4. The results of the scientific research shall be published irrespective of whether they are favourable to the client.

5. The scientist shall always be free to publish the findings of the research within a specified reasonable period of time. In this context two months can be regarded as a reasonable period, with six months generally the maximum (this period being calculated from the moment that the final results are submitted to the client). An exception should be made where there are issues of intellectual property in which case a period of no longer than 12 month would be acceptable.

6. The methods of publication shall be stipulated in the contract. Publication in a scientific journal shall take place in consultation with the client, but the researcher shall have the final say on the contents, the authors, the form of publication and where the research will be published.

7. External financiers of research assignments and/or other sponsors shall be mentioned by name in publications and other forms of disclosure.

8. Relevant interests and/or advisory relations of the researcher(s) shall be cited in publications and other forms of disclosure.

9. The text of the contract shall be available for inspection in confidence by the National Council on Research Integrity (LOWI).

 

*This Declaration forms the heart of the code of conduct proposed by the Royal Netherlands Academy of Sciences.

Source: Van der Meer J et al, 2007.11

References

1. Greenberg DS. Science for Sale The Perils, Rewards and Delusions of Campus Capitalism.Chicago, IL: University of Chicago Press; 2007.
2. Mervis J. NIH Shrinks, NSF Crawls as Congress Finishes Spending Bills. Science. 2006:311(5757):28–9. 
3. Reich RB. Supercapitalism: The Transformation of Business, Democracy, and Everyday Life. New York: Kopf; 2007. 
4. Curfman GD, Morrissey S, Drazen JM. Expression of concern: Bombardier et al., Comparison of upper gastrointestinal toxicity of rofecoxib and naproxen in patients with rheumatoid arthritis. N Engl J Med. 2000;343:1520-8. 
5. Brody H. Hooked: How Medicine’s Dependence on the Pharmaceutical Industry Undermines Professional Ethics. Rowman & Littlefield Publishers, Inc.: Lanham, MD; 2008.
6. Lesser LI, Ebbeling CB, Goozner M, Wypij D, Ludwig DS. Relationship between funding source and conclusion among nutrition-related scientific articles. PLoS Med. 2007 Jan;4(1):e5. 
7. Allen TJ. Merck’s Murky Dealings: HPV Vaccine Lobby Backfires. Special to CorpWatch, March 7th, 2007. Available at:http://www.corpwatch.org/article.php?id=14401. Accessed March 24, 2008. 
8. Campbell EG. Institutional academic industry relationships. JAMA. 2007;298(15):1779-86.
9. Lurie P. Presentation before the Institute of Medicine’s Committee on Conflict of Interest in Medical Research, Education, and Practice (HRG publication #1830). November 5, 2007. Washington, DC. Available at:http://www.citizen.org/publications/release.cfm?ID=7553
&secID=1656&catID=126. Accessed on March 24, 2008. 
10. Finder A. Some Campuses Decide Tobacco Company Money Is ‘Tainted.’ The New York Times. Feb 4, 2008. Available at:http://www.nytimes.com/2008/02/04/education/04tobacco.html. Accessed on March 24, 2008. 
11. van der Meer JW, de Gier AM, van Swaaij WP, Katan MB. Independent medical research. Neth J Med. 2007;65(4):124-6.

Do pharmaceutical marketing and pricing practices reduce compliance with cardiovascular medications?

Posted on by Corporations and Health Watch

Cardiovascular disease (CVD) is the most prevalent condition treated in primary care practice and contributes to the socioeconomic and racial/ethnic inequities in health that characterize the U.S. Treating hypertension and hyperlipidemia, CVD’s major risk factors, can significantly reduce the risk of severe cardiovascular outcomes. Although safe and effective medications are available for this purpose, maintaining healthy blood pressure and cholesterol is difficult, particularly for people from disadvantaged populations. Conventional wisdom says that providing free pharmaceutical samples should help patients to take their medicine but a recent study in Medical Care found that “individuals receiving samples have higher prescription expenditures than their counterparts.” The authors concluded that “these findings suggest that sample recipients remain disproportionately burdened by prescription costs even after sample receipt.”1 While there are many factors that contribute to this problem, here we examine the role of prescription medication marketing practices and costs on patient adherence to prescribed medications.

Adherence to prescribed medications for the control of chronic conditions may be particularly difficult for many disadvantaged populations for multiple reasons, including sociocultural influences that inhibit productive patient-physician communication, low health literacy, and difficulty adjustinglifestyle and health behaviors, among others. These factors have been described in the medical literature and are often the target of patient-level interventions. However another significant but less-studied influence on adherence is the inability of patients to consistently fill prescriptions because of cost of medications. Numerous studies have shown that lower income and/or uninsured patients frequently forgo needed medical care because of cost2,3,4,5,6 delay filling and refilling prescriptions because of cost,7 or share prescriptions with friends and family members because of cost.8 Given these data, we wonder why cost has been given so little attention, and propose that pharmaceutical industry marketing practices might be a factor in compliance.

The pharmaceutical industry continues to develop and market new classes of medications to treat hypertension and hyperlipidemia, even though effective medications to treat these conditions have been available for many years. While the new medications are typically considerably more expensive, they are heavily advertised for any improvement in effectiveness, specificity in their action, and reduced side effects than the earlier drugs. However, there are convincing data showing that in many cases established therapies can be about as effective as the newer medications for many patients.9,10 For example, the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial showed that thiazide-type diuretics are as effective as newer antihypertensive medications, such as an angiotensin converting enzyme (ACE) inhibitor, in reducing blood pressure and cardiovascular complications.9 We acknowledge that contradictory evidence also exists.11 Appropriate decisions about which of the available medication therapies should be prescribed to individual patients include clinical considerations, tolerance of side effects, and other patient-level factors. To date, cost seems to have been of less immediate concern for many prescribing physicians.

To understand why cost might not be routinely considered as a primary factor in clinical decision making, we must take a look at the way medications are marketed. The largest domain of pharmaceutical marketing is the direct promotion of medications to physicians by pharmaceutical representatives, termed “detailing.” Such interactions with pharmaceutical representatives are frequent, occur in multiple clinical settings, and begin as early as medical school. Pharmaceutical representatives have a well-established role in the clinical setting that may extend beyond educating physicians about new medications. Data indicate that this marketing behavior is likely to have had an impact on CVD treatment patterns in particular as the medications to treat its major risk factors are among the most marketed medications, and marketed medications tend to overwhelm the market share of all medications for a particular condition. For example, those medications that are marketed for hyperlipidemia account for about two-thirds of the market share of medications to treat this condition.12

A recent anthropological assessment argues that pharmaceutical representatives create a”culture of gift exchanges” in hospitals and clinics.13 Gifts can include early data on “cutting edge” treatments, supplies for both home and office, opportunities to attend professional conferences, staff lunches, and so on. Some analysts argue that this gift culture creates a conflict of interest for physicians, influencing them to make inappropriate clinical decisions. In this view, pharmaceutical representatives may negatively influence clinical practice not by encouraging physicians to ignore good clinical practice when prescribing medications (that is, accounting for clinical considerations, tolerance of side effects, and other patient-level factors). Rather, sales people may lead physicians to make questionable medication choices when factors other than these clinical benefits are the primary factors at stake. Specifically, interactions with pharmaceutical representatives may lead physicians to prescribe the newest and/or most costly medications to some patients for whom less expensive, cost-effective treatment alternatives are also available. (See Peay and Peay,14 for a discussion of this issue.) This practice would not only increase medical costs, but could also lead to poor medication access and adherence, and ultimately lead to poorer patient outcomes – particularly for the most disadvantaged patients.

So exactly how might pharmaceutical marketing practices mask real cost considerations? One way is the distribution of free product samples. Free samples of medication (“sampling”) are given to physicians to pass along to their patients, a key part of the gift culture previously described. The stated intent of sampling is to allow patients to have access to a free short-term trial of a new medication to determine drug tolerance, side effects, and clinical response, before making a commitment to purchase a longer term supply of the medication. However, physicians frequently report that they give samples in order to provide free or low-cost medications to their uninsured/underinsured patients.15,16

Studies suggest that most physicians recognize that medication cost may be a substantial barrier to patients’ ability to adhere to prescribed medication regimens, and believe that cost should be a consideration when making treatment choices for patients. (See Alexander et al.17,18,19 for discussions of this issue.) However few physicians actually take the necessary steps to adequately monitor either cost or cost-related adherence, by, for example, initiating conversations about medication-taking behaviors, the out-of-pocket costs of medications, and the potential for cost to be a barrier to filling or refilling prescriptions and medication adherence.17,20,21 For physicians who are made aware of cost concerns, the sample closet is frequently thought to be their only resource. Surprisingly few physicians are aware of strategies other than pharmaceutical sponsored medication samples to help patients reduce their financial burdens due to the cost of multiple medications.17,22 Alternatives can include suggesting behavior modification, prescribing generic medications, using pharmaceutical sponsored Medication Assistance Programs, and referring patients to 340B Drug Pricing Programs (federal programs that entitle health centers to purchase/distribute medications at Medicaid prices or lower). Thus, despite the concern about the problems associated with pharmaceutical marketing in general, many physicians strongly support “sampling.”

What is the harm of “sampling?” While potential harms have not yet been described fully, the availability of samples may influence medication choices when there are many medication options available to the physician. For example, while it is possible that use of samples encourages adherence to prescribed medications, it is also possible that the use of samples reduces adherence because patients who are used to receiving free samples only take these expensive medications when samples are available. Additionally, because the large number of uninsured/underinsured patients, the ongoing availability of samples cannot be assured. Thus, reliance on samples alone for uninsured/underinsured patients is an inadequate long-term strategy to provide access to pharmaceuticals. Additionally, the distribution of samples presents a great potential for medical errors due to inadequate labeling and record keeping, in addition to the previously discussed concerns about inappropriate treatment choices. Beginning in 2004, the Joint Commission on Accreditation of Healthcare Organizations requires that accredited health care organizations follow specific guidelines for managing medications that includes processes for ordering and prescribing, preparing and dispensing, administering, monitoring, selecting and procuring, and storing medications, including samples. Because the nature of relationships with pharmaceutical representatives was intentionally informal (as part of a “gift culture” described above), shifting the system of documenting the receipt/distribution of samples received from pharmaceutical representatives from an informal to a formal system has been difficult for many safety net settings.

We believe rigorously designed observational and experimental studies are warranted to determine whether the potential cost saving benefit of having samples available equals the potential harm that this practice might cause for the treatment of cardiovascular disease and its major risk factors in primary care settings. Such studies will also help to address the larger question about whether pharmaceutical marketing practices in general make it more or less difficult for physicians to address medication cost concerns of their patients, and, ultimately to improve adherence to necessary treatments for the major risk factors for cardiovascular disease and reduce health disparities.

Nancy Sohler, Ph.D., MPH, is an assistant medical professor of health policy at the Sophie Davis Medical School of the City University of New York.

Jonathan N. Tobin, Ph.D., is the President/CEO of Clinical Directors Network, a primary care practice-based research network and clinician training organization that works with medically underserved communities. He is also Professor and Director of Education and Training at the Institute for Public Health Sciences of Yeshiva University.

Andrea Cassells, MPH, is the Director of Clinical Affairs at Clinical Directors Network in New York City.

For More Information

Organizations working to change health harming practices of the pharmaceutical industry:

The Prescription Project 
Prescription Access Litigation 
Consumers Union Prescription for Change 
Marketing Overdose (Consumers International) 
Pushing Prescriptions (Center for Public Integrity) 
Center for Medical Consumers

 

References

1. Jackson JE, Doescher MP, Saver BG, Fishman P. Prescription drug coverage, health, and medication acquisition among seniors with one or more chronic conditions. Med Care. 2004;42(11):1056-65.
2. Wilson IB, Rogers WH, Chang H, Safran DG. Cost-related Skipping of Medications and Other Treatments Among Medicare Beneficiaries Between 1998 and 2000: Results of a National Study. J Gen Intern Med. 2005;20:715-20. 
3. Heisler M, Wagner TH, Piette JD. Patient Strategies to Cope with High Prescription Medication Costs: Who is Cutting Back on Necessities, Increasing Debt, or Underusing Medications? J Behav Med. 2005;28(1):43-51.
4. Klein D, Turvey C; Wallace R. Elders Who Delay Medication Because of Cost: Health Insurance, Demographic, Health and Financial Correlates. Gerontologist. 2004;44(6):779-87.
5. Kennedy J, Coyne J, Sclar D. Drug affordability and prescription noncompliance in the United States: 1997-2002. Clin Ther. 2004;26(4):607-14.
6. Piette JD, Heisler M, Krein S, Kerr EA. The Role of Patient-Physician Trust in Moderating Medication Nonadherence Due to Cost Pressures. Arch Intern Med. 2005;165(15):1749-55.
7. Jackson JE, Doescher MP, Saver BG, Fishman P. Prescription drug coverage, health, and medication acquisition among seniors with one or more chronic conditions. Med Care. 2004; 42(11):1056-65.
8. Bonuck KA, Memmott MM, Arno PS. Cost-Related Prescription Drug Misuse Among Older Persons. Health Aff.2001;20(5):241-51.
9. Davis BR, Piller LB, Cutler JA, Furberg C, Dunn K, Franklin S, Goff D, Leenen F, Mohiuddin S, Papademetriou V, Proschan M, Ellsworth A, Golden J, Colon P, Crow R, for the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) Collaborative Research Group. Role of Diuretics in the Prevention of Heart Failure: The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial. Circulation. 2006;113:2201-10.
10. Cheetham TC, Chan J, Benson V, Richmond C, Levin E, Campen D. Successful conversion of patients with hypercholesterolemia from a brand name to a generic cholesterol-lowering drug. Am J Manag Care. 2005;11(9):546-52.
11. Litchenberg FR. Are the benefits of newer drugs worth their cost? Evidence from the 1996 MEPS. Health Aff.2001;20(5):241-251.
12. National Institute for Health Care Management Foundation, Prescription Drugs and Mass Media advertising 2000(November 2001). 
13. Oldani MJ. Thick Prescriptions: Toward an interpretation of pharmaceutical sales practices. Med Anthropol Q.2004;18(3):325-56.
14. Peay MY, Peay ER. The role of commercial sources in the adoption of a new drug. Soc Sci Med. 1988;26:1183-99.
15. Spiller LD, Wymer WW. Physicians’ perceptions and uses of commercial drug information sources: an examination of pharmaceutical marketing to physicians. Health Mark Q. 2001;19:91-106.
16. Chew LD, O’Young TS, Hazlet TK, Bradley KA, Maynard C, Lessler DS. A Physician Survey of the Effect of Drug Sample Availability on Physicians’ Behavior. J Gen Intern Med. 2000;15(7):478-83.
17. Alexander GC, Casalino LP, Meltzer DO. Physician strategies to reduce patients’ out-of-pocket prescription costs. Arch Intern Med. 2005;165(6):633-36.
18. Alexander GC, Casalino LP, Tseng CW, McFadden D, Meltzer DO. Barriers to patient-physician communication about out-of-pocket costs. J Gen Intern Med. 2004;19(8):856-60.
19. Alexander GC, Casalino LP, Meltzer DO. Patient-physician communication about out-of-pocket costs. JAMA,2003;290:953-58.
20. Shrank WH, Fox SA, Kirk A, Ettner SL, Cantrell CH, Glassman P, Asch SM. The effect of pharmacy benefit design on patient-physician communication about costs. J Gen Intern Med. 2006;21(4):334-39.
21. Bokhour BG, Berlowitz DR, Long JA, Kressin NR. How do providers assess antihypertensive medication adherence in medical encounters? J Gen Intern Med. 2006;21:577-83.
22. Shrank WH, Hoang T, Ettner SL, Glassman PA, Nair K, DeLapp D, Dirstine J, Avorn J, Asch SM. The implications of choice: prescribing generic or preferred pharmaceuticals improves medication adherence for chronic conditions. Arch Intern Med. 2006;166(3):332-37.

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