Biotech healthcare is going through what every other emerging scientific discipline experiences – the challenge of defining its ethical boundaries.Research, costs, and privacy issues spawn concerns that third-party payers, employers, providers, and policy makers will face for years to come.
Ethical design of clinical trials was, by far, the most frequently cited ethical issue by our editorial board. Eric Wickstrom, PhD, says it is important to structure trials appropriately to obtain clear tests of hypotheses while protecting human subjects.
In an age when medical technology improves with increasing rapidity, the availability of new treatments increases almost as quickly. With advances, however, come dilemmas — scientific, financial, and especially moral. These conundrums are likely to multiply as groups with vastly different viewpoints and resources battle over the direction of health policy.
As the first decade of the 21st century reaches its midpoint, Biotechnology Healthcare has identified five topics that dominate ethical discussions of biotech medicine.1 These issues will continue to generate controversy in the foreseeable future, forcing third-party payers, employer and union purchasers, and health care providers to deal with the policy implications of some or all of them for years.
1. Protecting Human Subjects in Clinical Trials
This issue has generated considerable debate since 1999, when 18-year-old Jesse Gelsinger died while participating in a gene therapy trial at the University of Pennsylvania. The institution was widely criticized for failing to disclose crucial information on informed consent documents, relaxing criteria for accepting volunteers, and enrolling volunteers who were ineligible. The episode prompted a great deal of soul-searching among researchers and regulators, and many universities began implementing new standards as a result of the harsh spotlight that was cast on the clinical trial world.
In a 2002 article in Epidemiology Review, Jeremy Sugarman, MD, MPH, a professor of bioethics and medicine at the Johns Hopkins School of Medicine, wrote, “It is critical to ensure that research is conducted responsibly throughout the entire study cycle, from the way participants are selected to the way data are entered, analyzed, and reported. Attention to each aspect of research conduct is necessary to the success of the scientific enterprise and to the protection of study participants and others from unnecessary harm.”
Conundrum: At what point does cost sharing backfire? A 20 percent coinsurance on a $20,000 therapy may work actuarially but could foster patient nonadherence.
The issue, of course, is complicated, because patients — especially suffering patients — are willing to try something new, even when physicians acknowledge that a complete side-effect profile isn’t known, according to Eric Wickstrom, PhD, a professor of biochemistry and molecular pharmacology at Jefferson Medical College. This headlong rush by ailing volunteers, he says, necessitates rigorous protection by review committees, even before patients see an informed consent form. This is especially true, he says, for some vaccines and gene therapy.
“Gene therapy hasn’t really worked yet, and it necessitates a great deal of care,” explains Wickstrom.
The Gelsinger episode, though, raised another sticking point — financial conflicts of interest. In this case, the lead researcher, James Wilson, MD, failed to disclose in the consent form that he had founded a company that stood to profit from the research.
Arthur L. Caplan, PhD,2 who heads the Center for Bioethics at the University of Pennsylvania, stressed in a recent interview with Biotechnology Healthcare that researchers must ensure that clinical trials are not distorted by incongruous arrangements. In addition, he says, volunteers should not be recruited in a manner that would suggest that they are being paid bribes, as opposed to reimbursement for legitimate expenses.
The rising cost of healthcare — and the cost of medications in particular — is a political hot potato and will remain so. No matter what the U.S. Food and Drug Administration might say or attempt, a large swath of the public, their federal representatives, and their governors do not seem to believe the pharmaceutical industry’s argument that research and development are funded by today’s prices and that price controls could retard R&D.
The ethical concerns are likely to get still more heated when the value of expensive biotech treatments for chronic illnesses is debated. After all, a needed pill for cholesterol might cost $3 daily, which amounts to nearly $1,100 per year.Compare that to a biologic that carries a $20,000-per-year price tag — or something even more costly.
The cost of defending the United States against bioterrorism raises a host of issues, says David Krause, MD, of Vicuron Pharmaceuticals. “If we fund this, what are we not funding?” he asks. “And can we ever predict all the possible terror threats?”
“Affordability is, arguably, an issue across the board,” says Jeff Kimmell, RPh, vice president of healthcare services and chief pharmacy officer at drugstore.com, in Bellevue, Wash. “In the United States, we say we want the best [treatments].But it’s also an ethical dilemma. At what point will people say ‘Enough is enough?’”
This may place payers and purchasers, who are already struggling with the question of how much cost sharing is appropriate, on the defensive. Insurers and employers juggle actuarial concerns with the risks of patient nonadherence and its potential for poor clinical outcomes when coverage decisions are made. The ethical questions do not fit neatly into this decision-making process but, rather, transcend it.
What happens when some patients can’t afford the out-of-pocket share of a given treatment? What if an insurer declines to add a biologic to its formulary because of its acquisition cost? What happens when a patient on an expensive chronic therapy maxes out his lifetime insurance benefit? Such instances may not be the norm, but their possibility disturbs some experts who see a pivotal clash between patients and profits.
“It’s certainly an economic issue if biologics are priced so high that some patients are priced out of the market,” says Sean Nicholson, PhD, assistant professor of policy analysis and management at Cornell University. “Perhaps an insurer may not cover a particular therapy. If there’s nothing else the patient could take to save his or her life, or to improve quality of life, that’s a dilemma.”
Talk about a Pandora’s box. Protecting patient privacy is a growing concern, thanks to technology that is making it possible to decode the human genome.But as scientists become adept at deciphering a person’s genetic composition, it is increasingly likely that compromising information about a person’s future health is going to become available.
This creates enormous problems. For instance, it may become possible to know that a 5-year-old is going to develop serious heart disease later in life, but does a prospective employer have the right to know that? How will this knowledge affect the individual’s ability to obtain a job, insurance, or a mortgage? Should such information be available to insurers and others? This is a thorny problem destined to become only thornier.
“Take a genetic test that comes back positive, and the biologic treatment of the patient costs $1 million,” says F. Randy Vogenberg, RPh, PhD, senior vice president and national practice council leader at Aon Consulting, in Providence, R.I. “What does an insurer do with that knowledge? It can’t tell the employer, but it does have a fiduciary responsibility as the health plan to remain within stated benefit coverage premiums and costs.
“It’s going to be very tricky for health plans to deal with this. And it won’t just be on a case-by-case basis, but it will come up during plan renewals and bidding.”
Sound far-fetched? Not really, says Vogenberg. “Generally speaking, everybody so far has stuck their heads in the sand. HIPAA offers some protection, but as diagnostics expand, this issue will bubble to the surface. And probably, litigation will determine some boundaries.”
To nip the problem in the bud, some attempts are being made to put rules in place now. An American College of Physicians working group published one such effort in the Annals of Internal Medicine in July; an article titled “Ethics in Practice: Managed Care and the Changing Health Care Environment” spelled out a statement of ethical principles for health plans, purchasers, and physicians.One section opined that “All parties have an ethical obligation to protect the confidentiality of patient health care information. In general, identifiable patient information should not be shared without the patient’s consent — except where the health and safety of individual persons or the public may be threatened, or as required by law.”
Conundrum: What does an insurer do with the knowledge that a person is predisposed to a condition that costs $1 million to treat? It can’t tell the employer, but it has a fiduciary responsibility to remain within stated benefit coverage premiums and costs.
Even this statement, however, leaves open the question about the extent to which an individual’s rights may be eclipsed by societal needs. This is especially true in the wake of the Patriot Act. In reflecting public fears about terrorism, the federal law is causing a raging debate over an individual’s right to privacy and the safety concerns of a society at large. With legal challenges pending, it is easy to see how even the ethics statement for managed care may cause difficulties.
4. Stem Cell Research
This one shouldn’t be a surprise. Stem cell research is anathema to the religious right and worked its way into the recent presidential election.
To circumvent the funding roadblocks in Washington, D.C., some states — such as New Jersey and California — are looking past ethical objections and taking serious steps to foster establishment of stem cell research centers. In California, birthplace of the biotech revolution and a state hard hit by the dot-com collapse, voters sized up the potential economic value of stem cell research and overwhelmingly passed Proposition 71, which guarantees $3 billion in state funding over the next decade.
It is somewhat ironic that a scientific area of research based on trials and data could be reconfigured into an emotional issue. The debate, of course, pits people who believe the research may one day find cures for diseases against others who say it violates human life.
On one side, the American Society of Clinical Oncology issued this policy statement in 1999: “Whether privately or publicly funded, researchers should be mindful of the ethical issues that may be raised when research involves embryos, fetal tissue, cloning, or other controversial questions. Nevertheless, medical research often requires a balancing of perceived risks against potential benefits.The tremendous potential of stem cell research for the treatment of diseases ...means that the balance of benefits and risks is now clearly in favor of going forward with the research, even if it involves ethically sensitive areas.”
On the other hand, the founding statement of Do No Harm – The Coalition of Americans for Research Ethics argues: “Stem cell research promises great good and is a worthy scientific priority as long as we pursue it ethically. Obtaining stem cells from people without seriously harming people in the process can be ethical. However, obtaining stem cells from human embryos cannot be ethical because it necessarily involves destroying those embryos.”
For now, say experts, the debate is largely hypothetical for insurers.
“Although it is still early in the process, it is likely that the managed care industry will continue to monitor this ethically sensitive area, particularly as the potential benefits and costs begin to outweigh the risks,” says Mitchell P. DeKoven, manager of reimbursement services at PharmAnalysis Group, MED-TAP’s Center for Pricing & Reimbursement, in Arlington, Va.
5. Defending the United States Against Bioterrorism
Security is hugely important, and public fears over terrorism are unlikely to diminish. In response, the federal government wants Project Bioshield to spur the development of treatments, including preventive medications and vaccines, that would be available in sufficient quantities to protect the largest possible number of people.
The congressional impetus is obvious, according to Chuck Ludlam, general counsel on the staff of Democratic Sen. Joseph Lieberman of Connecticut. In a recent speech, Ludlam said that economic losses caused by a successful bioterror attack in a densely populated area could be massive.
But Project Bioshield also raises ethical problems, experts say. For starters, the investment will be large and probably will grow over time. At a time when deficits are growing, generous funding for bioterrorism research suggests that funding for other public health priorities — such as diseases that are becoming more prevalent — may suffer.
“If we fund this, what are we not funding? And how do you divide the pie?” asks David Krause, MD, senior vice president of clinical research and medical affairs at Vicuron Pharmaceuticals, in King of Prussia, Pa. “And that’s just part of the problem. We don’t know if anybody will ever die from bioterrorism. We don’t know what the threat is. Can we ever predict all the possible terror threats and provide protection against them?”
Krause isn’t alone in observing that there is an unpredictable number of portals for bioterrorists to wreak havoc on the United States. The Infectious Diseases Society of America wants the scope of Project Bioshield extended to include all areas of infectious disease research and development, especially for antibiotics to treat existing drug-resistant infections.
“There is an inextricably linked, synergistic relationship between research and development efforts needed to protect against both naturally occurring infections and bioterrorism agents,” said John Bartlett, chief of the division of infectious diseases at the Johns Hopkins School of Medicine and chair of an IDSA task force, in testimony given recently before the U.S. Senate Committee on Health, Education, Labor and Pensions, and the Senate Judiciary Committee.
On the positive side, bioterrorism research may yield the same sort of consumer-product payoff NASA research did — in this case, Ludlam noted, possibly indirectly helping to find medicines to treat infections with HIV and viruses that cause hepatitis, Lyme disease, polio, West Nile, and the common cold. The effort also could lead to medicines for bacteria, such as those causing tuberculosis, pneumonia, salmonellosis, malaria, sepsis, or sexually transmitted diseases.
A subsidiary ethical issue to bioterrorism research, says Krause, is clinical testing. Human subjects couldn’t be used in smallpox trials, for instance, so surrogate markers are required. This can make it difficult to determine the effectiveness of an antiterrorism agent.
“We’re talking about an expensive insurance policy and, like any insurance policy, you hope you never have to use it,” says Krause. “You want it in your plan, but at the same time, it’s not a slam dunk.”
1About our methodology: The editors selected and ranked the five broad topics in this article on the basis of the results of a questionnaire distributed to the Biotechnology Healthcare editorial board. The editorial board (see page 3) represents numerous disciplines, and includes physicians, pharmacists, researchers, ethicists, insurers, managed care executives, employers, government policy experts, and consultants.
2Astute readers will recall that Caplan had a courtesy appointment to Wilson’s department and provided him with informal advice about enrolling patients in gene therapy trials. Caplan, who has been active in his career in pushing informed-consent reforms, ultimately was found to have no responsibility in the Gelsinger case.