It is no surprise to anyone that health care spending continues to rise at what is generally considered the fastest rate in U.S. history. As a result, the health care industry is growing exponentially and is under incredible market pressure. Medical device companies and pharmaceutical companies constantly compete to provide newer and better drugs and devices as well as balance issues relating to cost, patient safety and liability.
In order to compete in this environment and develop safe and effective products, testing on human volunteers through clinical trials is necessary. Naturally, because they involve human beings, clinical trials have increasingly become the subject of litigation. Due to the rise in our aging population and the market pressures incumbent on medical and pharmaceutical companies, it is anticipated that we will continue to see numerous clinical trials as well as the ensuing litigation based on clinical trials well into the future.Lawyers have crafted numerous, varied and often creative attempts to file suit on behalf of the subjects or former subjects of clinical trials. This article discusses the various causes of action seen in courtrooms around the United States and whether such causes of action have been successful.A BRIEF HISTORY OF REGULATIONSFirst, a brief discussion of the history of some codes and regulations applicable to clinical trials may be useful.The intellectual beginning of the ethical code protecting human subjects began in 1949 with the Nuremberg Code, which was developed for the Nuremberg Military Tribunal as the standard for evaluating human experimentation conducted by the Nazis. The Nuremberg Code states, “[T]he voluntary consent of the human subject is absolutely essential.” It provides details on issues such as the capacity to consent, freedom from coercion and the comprehension of the risks and benefits involved in taking part in experiments on humans.The Declaration of Helsinki, made in 1964, was the next worldwide document involving human research protection. The World Medical Association developed the declaration as a statement of ethical principles that would provide guidance to physicians and other participants in medical research involving human subjects.Finally, in 1979 the United States issued the Belmont Report, authored by the National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research. The report was codified in Title 45, Part 46 of the Code of Federal Regulations in 1981, which is now known as “The Common Rule.” The Common Rule sets forth the basic elements of informed consent, which include:1) A statement that the study involves research, an explanation of the purposes of the research and the expected duration of the subject’s participation, a description of the procedures to be followed and identification of any procedures that are experimental;2) A description of any reasonably foreseeable risks or discomforts to the subject;3) A description of any benefits to the subject or to others that may reasonably be expected from the research;4) A disclosure of appropriate alternative procedures or courses of treatment, if any, that might be advantageous to the subject;5) A statement describing the extent, if any, to which the confidentiality of records identifying the subject will be maintained;6) For research involving more than minimal risk, an explanation as to whether any compensation will be provided along with an explanation about whether any medical treatments are available if injury occurs and if so, what they will be;7) An explanation of whom to contact for answers to pertinent questions about the research and research subjects’ rights, and whom to contact in the event of a research-related injury to the subject; and8) A statement that their participation is voluntary, refusal to participate will involve no penalty or loss of benefits to which the subject is otherwise entitled and the subject may discontinue participation at any time without penalty or loss of benefits to which the subject is otherwise entitled. 45 C.F.R. � 46.116(a). The Common Rule goes on to provide for several additional elements of informed consent, which shall be provided to the subjects when appropriate, including a statement that the treatment or procedure may involve risks that currently are unforeseeable.It is clear that the legislature and international organizations place tremendous emphasis on fully informing subjects of clinical trials of their rights in order to ensure that their participation is voluntary. Because true informed consent is considered so important for these subjects, litigation over clinical trials usually involves at least some element of failure to provide for informed consent.INFORMED CONSENTVoluntary and informed consent is of paramount importance to any ethical clinical trial. As a result, many of the lawsuits involving clinical trials allege a lack of informed consent. If a research subject is not fully informed and the applicable regulations regarding informed consent are not followed, a plaintiff may argue that this constitutes negligence per se.The California case of Daum v. Spinecare Medical Group Inc., 52 Cal.App.4th 1285 (1997), arose out of an unsuccessful spinal fusion surgery on Mr. Daum, who filed suit and alleged that Spinecare failed to obtain informed consent. Daum claimed he was not informed that the device used in the surgery was considered investigational or experimental, nor was he told that the surgery was part of a United States Food and Drug Administration approved clinical investigation. At trial the plaintiffs requested that the trial court charge the jury with the negligence-per-se instruction, but the court refused to do so.The California Court of Appeal discussed the requirements of negligence per se in detail and concluded that the failure of the physician to make the disclosure required by the federal regulations was supported by substantial evidence. Further, it was clear that Daum would not have participated in the clinical trial if the proper disclosures had been made.The court held that all four elements of the negligence-per-se doctrine were sufficiently established and the trial court was required to charge the jury regarding negligence per se. The court stated that the legislature and the FDA, “in their wisdom,” had promulgated requirements for informed consent and that “[n]either physicians nor courts are free to disregard these requirements.” Id. at 1306.Based on the teachings of Daum, a plaintiff may argue that the failure to follow FDA regulations may give rise to a claim of negligence per se. Physicians, investigators and institutional research boards (IRBs) need to carefully and closely follow all FDA regulations and IRB recommendations regarding informed consent.Hospitals may also be held liable for inadequate consent. In Lenahan v. University of Chicago, 348 Ill.App.3d 155 (2004), the hospital and the University of Chicago adopted policies and established an IRB to ensure that the consent forms for a clinical trial complied with the applicable FDA and Department of Health and Human Services regulations. The Lenahan court held that the plaintiff had adequately stated a cause of action against the university and against the hospital related to the allegedly inadequate consent, and upheld the trial court’s denial of these defendants’ motion to dismiss.In addition, the court held that the physician sponsor and principal investigator of the clinical trial could be held liable for failing to obtain valid informed consent, even though the doctor never personally met with the patient and did not perform any services unique to the patient. The court found that the plaintiff sufficiently pled a physician-patient relationship between the physician and the decedent by alleging that the physician provided services to the decedent, conducted laboratory tests and reviewed test results.The good news for defendants, however, is that even with informed consent claims, the plaintiff must still prove causation of his or her specific injuries; in order to survive summary judgment the plaintiff is required to show that the defendant’s negligence caused the injuries alleged. Causation cannot be based on general statistical information for a particular clinical trial. See Compton v. Pass, 2006 WL 2419187 (Mich. App. 2006).In addition, the defendants in clinical trial cases do not seem to have any duty to inform the patient about clinical trials which may not be available. The courts in Pennsylvania and California have held that where there is no evidence that an applicable clinical trial exists, or when a clinical trial exists that is outlawed in the plaintiff’s particular state, the physician does not have a duty to inform the patient of the availability of other possible clinical trials. Schiff v. Prados, 92 Cal.App.4th 692 (2002); Herb v. Spock, 2005 WL 2834242 (Pa. Com. Pl. 2005).ATTEMPTS TO COMPEL TREATMENTIn addition to lawsuits for lack of informed consent, there have been some recently filed lawsuits in which the patients sought to compel the manufacturer or clinical trial sponsor to continue to provide them with the treatment or drug after the clinical trial has been terminated by the manufacturer. These attempts have been unsuccessful thus far; however, one can be certain that we have not seen the last of such claims.In the two related cases of Suthers v. Amgen Inc., 372 F.Supp.2d 416 (S.D.N.Y. 2005), and Abney v. Amgen Inc., 372 F.Supp.2d 416 (S.D.N.Y. 2005), two subjects were participating in a clinical drug trial that involved a drug to treat Parkinson’s disease. In September 2004, Amgen, the drug manufacturer, announced it was terminating all clinical use of the drug based on two scientific concerns. The first concern was that several study participants had developed antibodies neutralizing a naturally occurring chemical in the body, which may result in irreversible damage to vital organs. The second discovery was that several primates used in a long-term study of this drug developed lesions in their cerebellums.Based on their belief that the experimental drug was working for them, the plaintiffs brought suit against the drug manufacturer seeking to compel the manufacturer to resume treatment and continue providing them with the drug after the termination of the clinical trial. The plaintiffs in both cases applied for a preliminary injunction requiring Amgen to provide the drug to the physicians conducting the research studies at the New York University and the University of Kentucky and allow the doctors to continue to administer the drug to the plaintiffs.Both plaintiffs advanced three legal theories to support their motions for an injunction. First, they claimed that the drug was beneficial to them and that Amgen was contractually obligated to supply them with the drug. The courts in both cases held that there was no breach of contract claim. The Abney court held that Amgen did not sign the informed consent document, which was the primary basis for the plaintiff’s breach of contract claim, and that the principal investigators were not agents of Amgen for purposes of this study. The Suthers court held that the patients knew their participation in the study was not a matter of right, based upon the consent form, and that the study could be terminated by the manufacturer at any point in time. The court stated that even though the company invested millions of dollars to test the drug, a contract did not exist in which “Amgen bargained away the freedom to terminate the research trials in its sole discretion.” Suthers v. Amgen Inc., 372 F.Supp.2d at 425.Both of these cases also included a claim for a promissory estoppel. The plaintiffs alleged that the principal investigators informed them that they would make decisions based on the patients’ best interests and that, if the drug proved to be safe, the participants could continue to receive the medication following the termination of the study. Both courts denied the claims: The court in Abney held that the plaintiffs had not submitted any evidence of a clear promise by the manufacturer to continue to provide them with the medication after the trial’s termination and that the investigators were not agents of Amgen; the Suthers court held that neither the text contained in the consent documents nor any assertions made by the physicians established a promise that could have induced detrimental reliance.Finally, in the Amgen cases, the plaintiffs alleged a breach of fiduciary duty and, again, both plaintiffs were unsuccessful. Both courts held that there was no fiduciary relationship between the sponsor of a research trial and the participants. In Suthers the court held that “[t]he fiduciary duty envisioned by the plaintiffs would presumably mean that if it were in a study participant’s best interest to continue a clinical study, then the sponsoring company would be without power to terminate it without risking a finding of breach.” Suthers v. Amgen Inc., 372 F.Supp.2d at 429.For those conducting clinical trials, the outcomes of these two cases are good news. However, they probably are not the last word.CONSTITUTIONAL DUE PROCESSSeveral cases involving clinical trials have attempted to assert constitutional due process claims. In Robertson v. McGee, 2002 WL 535045 (N.D. Okla. 2002), the plaintiffs alleged their constitutional claim as “a violation of their privacy right ‘to be treated with dignity’ and their liberty interest in due process.” They alleged their claims arose under � 1983 due to the deprivation of their right to be treated with dignity and the federal regulations for the protection of human research subjects.Although the court in Robertson admitted that the plaintiffs’ claims were somewhat unclear, they appeared to be alleging that, by conducting the study in violation of federal regulations, the defendant’s conduct gave rise to an independent cause of action by incorporating the Declaration of Helsinki and the Nuremberg Code. The plaintiffs claimed these international laws were the “minimum international standards of conduct governing biomedical research on human subjects into which all the citizens of all nations are subject.”The court held that there is no private right of action for an alleged violation of international law under either the Declaration of Helsinki or the Nuremberg Code. It also held that there is no private right of action under 45 C.F.R. Part 46; therefore, � 1983 could not create a private right of action that otherwise did not exist.In the case of Wright v. Fred Hutchinson Cancer Research Center, 269 F.Supp.2d 1286 (D. Wash. 2002), the plaintiffs asked the court to find that their participation in a clinical trial could give rise to a constitutional violation for failure of the treating physician to adequately inform the patient of the risks, benefits and alternatives to the treatment, as well as potential conflicts of interest unrelated to the treatment itself. The court held that a lack of informed consent in the medical context was not a constitutional violation and the plaintiffs only option was to seek any damages recoverable under the state’s informed consent statute. The court further held that the defendant’s “failure to make disclosures necessary to the informed consent process in a therapeutic experimental setting does not implicate rights that are so rooted in the tradition and conscience of our people as to be ranked as fundamental.” Wright v. Fred Hutchinson Cancer Research Center, 269 F.Supp.2d at 1296.Once again, defendants may be reassured that the courts in the above cases have not found any constitutional violations and do not believe that the allegations involved any fundamental rights.CONCLUSIONClinical trials are absolutely necessary for medical research because the information gleaned from experiments on human subjects is required to ensure that medical devices and drugs are safe and effective. The goal of these trials is to provide the public with innovative and safe products whose benefits outweigh their risks. Informed consent is the most important, and potentially the easiest, way to minimize exposure to liability for all parties involved in clinical trials.Although litigation can be anticipated, clinical trials ultimately serve to advance medicine and develop newer and better medical products and treatments and are invaluable medical research tools. Steps can be taken to decrease liability exposure. All participants in clinical trials will benefit from full, freely given and informed consent. In addition, researchers must strive to adhere to established standards of conduct and approved protocols for their particular trial. Clearly, as in all medicine, all results, actions and interactions with patients must be clearly documented.Carrie N. Lowe is a partner in the Atlanta office of Carlock Copeland Semler & Stair.