At the end of every developmental process in which the intent is to provide a new therapy or to understand a clinical condition better, there is a need to perform experiments on patients. Human experimentation is a necessary part of orthopaedic research, and orthopaedic investigators must recognize that the treatment of patients in clinical trials is neither simple nor intuitive. Clinical research requires the understanding and practice of ethical principles and methods of conduct that have been developed and refined over the past fifty years. These principles govern not only the scientific research process but also the ethics of clinical investigation.
On this, the fiftieth anniversary of the Doctors Trial at Nuremberg, we have an opportunity to reflect on the power of clinical research and the current issues confronting human experimentation. The tenuous nature of a concept such as voluntary consent, the intensity of the profit motive in the health-care industry, and the possibility that an investigator may view research involving human experimental subjects as a means to his or her own ends require our attention and self-analysis. The advances that have been made in research technology and the sophistication of current techniques should not lull us into a sense that we understand equally well the ethics and the conduct of human experimentation.
In 1933, when the National Socialist Party came to power in Germany, that country's medical profession was among the most sophisticated in the world. Physician participation in the design and implementation of Nazi programs of human experimentation was extensive. By their active involvement and acquiescence, the medical profession raised profound questions about medical ethics. A major lesson from the Nazi era is the fundamental ethical basis of science and medicine and the importance of an informed and concerned profession1.
In today's clinical research setting, information concerning informed consent usually is presented to the patient by a physician who is trying to encourage participation in the study. It is sometimes difficult for the physician, who in this case is the investigator, to be impartial to his or her role in the process. Guidelines are necessary for the conduct of this critical part of the experimental design. In this issue of The Journal, Fuson et al. provide some help in this area. In their Current Concepts Review, they refer to the original statement delimiting permissible medical experimentation on human subjects under the Nuremberg Code and provide (in the Appendix) the World Medical Association Declaration of Helsinki, which was adopted in 1964 to guide physicians in biomedical research involving human subjects. (The Nuremberg Code recently was reprinted in another publication3.) We encourage our readers to study these documents carefully and to consider their meaning and ramifications. Because both the Nuremberg Code and the Declaration of Helsinki are international documents, it is inappropriate for the reviewers, editors, or readers of The Journal to draw the conclusion that cultural differences can dictate the conduct of human clinical experimentation. Although politics may set standards for human rights in some cultures, the international medical community must rise above this quagmire and set standards to which all clinical investigators must adhere.
The Journal has adopted a policy that it will not publish an article in which the standards of human experimentation, which include informed consent and human rights, are not carefully presented, delineated, and followed. Every manuscript reviewed by The Journal should contain a paragraph in the methodology section that explains the informed-consent process. This can be a short paragraph, but it must be included within the body of the scientific work and not as a footnote or as a separate statement. Physicians and scientists must become accustomed to including the concept of protection of human rights during an experiment so that it becomes a routine part of the methodology. In addition, it must be emphasized that every experiment needs some form of monitoring; no experiment involving human subjects can be assumed to be so benign that it need not be reviewed.
The involvement of a patient in an experiment demands that a physician be the patient's strong advocate and protect him or her from the dangers of the experiment and from the potential abuses of the research process. The pre-experiment review procedure also must ensure that the resulting data will be a worthwhile outcome of the process. For example, conducting experiments on small groups in which the number of subjects is insufficient to provide the necessary statistical power yields results that may be of limited scientific value. In such cases, it is unethical to expose the patient to any of the risks associated with either the treatment or the experiment. Another concern is the use of a new treatment for a medical problem for which the existing forms of treatment are quite good. For example, when one wishes to test a new internal fixation device to treat an intertrochanteric fracture of the hip and the control group might be treated with a sliding screw-plate device (a device that has been shown to be successful in most patients), it is an ethical challenge to design an experiment and provide appropriate informed consent. This is more ethically challenging than testing a new drug to treat a condition such as thrombophlebitis, which remains an unresolved problem, or evaluating a growth factor that stimulates bone formation in patients who have loss of bone because of trauma or neoplasia.
Any manuscript submitted to The Journal that does not contain the necessary assurances regarding human clinical experimentation will be rejected regardless of the value of the data, the validity of the experiment, or the authors' opinion of the consequences to the patient. Even experiments in which two forms of an accepted orthopaedic treatment are compared with each other will not be accepted unless it is clear that the patients understood that they were part of an experiment and that all of the assurances regarding human clinical experimentation were provided and maintained.
This is a critical time in the history of human experimentation. The unconditional commitment to the informed-consent process is at risk of being ended by our enthusiasm over a belief that investigational devices and drugs may be the cures to our most difficult problems. We in the orthopaedic community must pause to revisit these issues and refresh ourselves as investigators.
Thomas A. Einhorn, M.D.
Deputy Editor for Current Concepts Reviews
Albert H. Burstein, Ph.D.
Deputy Editor for Research
Henry R. Cowell, M.D., Ph.D.
Editor