Just because it's new doesn't mean it's best

Your patient has achieved successful pharmacological management of a chronic condition and reports negligible side effects from the drug. A new drug is introduced for the same condition and promoted with claims that it is more effective. The new drug is more expensive, but your patient's insurance will cover it. How do you decide whether to try your patient on the new drug?

Reply:

The simple answer to this question is, "Of course I would not use a more expensive medicine to replace an effective one with no side effects." But in fact such substitutions do occur, and frequently. The drug companies count on it.

Several issues invite consideration. Foremost among them is the fact that the physician is expected by the patient and society to make all clinical decisions for the benefit of the patient's welfare. Our profession embraces this principle; it is the bedrock of our ethical code.

Because there is a finite amount of money in the medical care system, spending more money on one endeavor leaves less for other efforts. It is in the best interest of both our patient individually and all patients collectively to spend less rather than more for an effective drug.

It may be difficult to decide if a new drug possesses novel desirable properties. We should and often do recognize information from drug companies for what it is -- advertising; biased information designed to promote purchase of the product. Also be wary of industry surveys or "consulting panels" that pay (often significant sums) for participation. They are virtually always marketing tools attempting to disguise themselves as education or information gathering.

Industry may offer gifts varying from trinkets to meals to items of substantial value. A few physicians protest that these inducements do not affect their judgment, but there is preponderant evidence that gifts of any value alter prescribing behavior. The AMA guidelines (AMA Code of Medical Ethics, Opinion 8.061) are generally accepted standards for professional behavior for those who choose not to avoid all contact with industry.

So physicians turn to the literature. Clinical trials often are financed by industry. Disclosure of financial and other conflicts by the authors is now standard. Disclosure, however, may not be sufficient to eliminate bias. Studies funded by industry consistently show more favorable outcomes for the experimental treatment than nonindustry-funded studies. This may be due partly to publication bias; studies that show no therapeutic benefit are less likely to be published.

Recently a number of prestigious journals have agreed not to consider publishing clinical trials unless the authors have agreed in advance to participate in a registry that presents data from all studies, including those that either were not submitted for publication or were submitted but not accepted. Unfortunately not all journals yet have this policy.

Few practicing physicians have the skills to analyze raw data accurately. We tend to trust the peer review screening process. This trust might be justified for the more prestigious journals, but many journals have less rigorous peer-review standards. There is always the possibility that those who do the peer review have financial and other conflicts.

Some journals disclose reviewer conflicts of interest, but most do not. Editorials often evaluate new data and offer opinions about validity. Some journals have tried to get authors without conflicts to write these editorials but on occasion have found that every expert in the particular field has a conflict.

Realizing that the literature is not always a reliable source of unbiased information, doctors turn to "practice guidelines" issued by specialty societies. Guidelines may be based on rigorously performed trials, but many guidelines are consensus statements representing the best opinion of recognized experts.

While these guidelines carry the imprimatur of the sponsoring organization and are generally reliable, the authors of the guidelines may have undisclosed conflicts.

In September, the American Council for Continuing Medical Education issued new regulations ensuring that information transmitted in a format acceptable for CME credit is as free from commercial bias as possible.

So how can doctors protect their patients in this imperfect world?

• Remember that doctors, not industry, have the responsibility to make decisions in the best interests of patients.
• Consider information from the drug industry as advertising with inherent bias.
• Use the least expensive therapeutically equivalent drug.
• Be wary of industry gifts. Follow accepted national guidelines.
• Read the literature with critical judgment. Look at the disclosures of the authors. Read the best journals.
• Utilize practice guidelines issued by major national specialty societies.
• When possible, obtain information from sources that offer CME.

Using the above criteria, I suspect the answer to our question remains the same as the one common sense originally dictated -- don't switch.

Herbert Rakatansky, MD, clinical professor of medicine at Brown Medical School, Providence, R.I.; gastroenterologist; former chair of the AMA Council on Ethical and Judicial Affairs

Reply:

The practice of medicine requires clinical judgments within the context of an inexact and complex science, judgments that have profound implications for the welfare of patients. The ethical question in this scenario is whether a physician can justify changing medications for the sake of research or other interests, as long as the patient is at low risk for harm. My response is that any clinical decision is ethically defensible only if it is reasonable to think that it is in the best interest of the patient; all other interests remain secondary.

In this case, it is difficult to justify a decision to discontinue an effective therapy that is free from side effects and replace it with one that is unproven and has unknown risks. For this patient, such a change would be experimental and comparatively risky. To ethically justify it would require an uncoerced and reasonable request by the patient to make such a change. Even then, the physician must consider the patient's safety.

The physician's first responsibility is to the welfare of the patient, even though participation in clinical research and the use of new treatments are necessary for the good of present and future patients. Physicians, as scientists, are sensitive to this need, as are drug companies. When being "detailed" by salespeople about a new and promising drug, however, separating truth from marketing hype is often difficult. Product information, though scientifically grounded, may be skewed in favor of the product, and it's difficult to predict all the risks and benefits. Independent reading and review of the evidence, anecdotal feedback from colleagues, and the use of consultants, who are often better versed in the newer drugs, are helpful in ensuring an unbiased and informed decision.

New products are developed in clinical trials. Industry-funded trials may offer promise and are not without scientific merit, but bias and conflict are unavoidable when the obvious interest of drug trials is in obtaining "good data" that support a product. Financial incentives for physicians who enroll patients also create a milieu of ethical peril when enrollment is driven by self-interest.

Promising drug trials may also offer hope for patients with chronic illness when conventional therapies have failed, or patients may volunteer to participate through a sense of altruism. In the case at hand, however, the patient is clinically stable and doing well, so neither condition applies. On balance, a recommendation to change pharmacological management is not medically indicated.

The economic argument that neither the patient nor the health care system will be greatly impacted cannot be ethically supported. Though the patient's insurance company will pay for the new drug, to ignore cost and expense at all levels sidesteps the physician's obligation to maintain fiscal prudence in prescribing practices with respect to scarce resources and the rising cost of health care.

As physicians, we have power to influence the thinking of our patients, who often decide based on our recommendations. They trust us to use our skill and knowledge primarily for their welfare. When other incentives, such as financial gain or scientific curiosity, drive our recommendations, the trust relationship is threatened because interest in patient welfare may no longer be paramount.

The art of medicine entails selecting wisely among myriad therapies, new and familiar, with the goal of serving the welfare of the patient above all other interests, including those of clinical research, the corporation and society. Best practices derive from rational, evidence-based decision-making, balancing economic concern, diagnostic elegance and therapeutic parsimony -- self-interest aside. Patient welfare therefore should not be suborned, even by well-intentioned desires for better science.

This patient has achieved successful pharmacological management of a chronic condition, has negligible side effects from the drug, and is, apparently, satisfied. Therefore there is no indication to change.

For the physician to recommend otherwise at this juncture would be ethically dubious unless sound evidence supports doing so or unless the patient altruistically and freely chooses to take new or experimental therapy after being fully informed of the risks and benefits of doing so. Even then, doing so requires the highest level of concern and monitoring for the safety and welfare of the patient.

David A. Fleming, MD, associate professor of medicine, Dept. of Health Management and Informatics, director of the Center for Health Ethics, University of Missouri-Columbia School of Medicine