Conclusion of U.S. Government's Inquiry into HSPH Genetic Research in China
For immediate release: May 30, 2003
In a letter dated May 2, 2003, the U.S. Office for Human Research Protections (OHRP) has informed us that its last few remaining questions have been resolved, concluding its investigation of Harvard School of Public Health’s genetic and environmental epidemiological studies in China. The letter acknowledges the remedial plans that were put into effect two years ago to strengthen HSPH procedures and oversight of the studies, and requires no further actions from Harvard. The letter concludes that, "As a result of the above determinations, there should be no need for further involvement of OHRP in this matter."
"We are gratified that the lengthy and detailed OHRP investigation has reached its conclusion," said HSPH Dean Barry R. Bloom. "We have worked diligently over that time to examine every aspect of our human subjects research and to make many changes that would improve our processes. Our China studies were observational in nature, not clinical trials: No drugs, devices or procedures were being tested. There were no experimental treatments involved. As we had hoped, the inquiry found no harm to any individual participants in the studies. We believe that, in response to OHRP’s queries, the improvements put into place to sharpen our oversight of all research involving human subjects, in the end, have established the kind of professional collaboration respectful of the safety of our study populations and of the integrity of our processes that we all strive for. Harvard seeks to ensure the highest level of protection of human subjects in all its work and will continue to endeavor to meet that standard."
Dean Bloom added: "We are enormously grateful to our collaborating partners in China, including Anhui Medical University and Beijing Medical University, for their patience and cooperation throughout the three and one half years of this investigation. We are grateful to members of the Chinese Human Genetics Resource Administration for their willingness to share their knowledge and experience with us in this effort. We look forward to continuing our partnerships in China."
"For reasons of distance and culture, international collaborations are complex and challenging, but all the more worthwhile for the knowledge they bring," said Harvard University President Lawrence Summers. "We learned through this inquiry how better to supervise our studies abroad to meet the highest standards of human subject protection. In light of the concerns I expressed last year, I was particularly gratified to learn from our internal inquiries and those of OHRP and others that the inquiry revealed no substantive harms done in our study and that all procedural concerns raised have been fully addressed. It also has been reassuring to find in this process that our colleagues in China have been so strongly committed to the protection of study participants, and we look forward to continuing our collaboration in many areas of research, scholarship and training."
The OHRP investigation began more than three years ago in response to a complaint from a former HSPH faculty member who alleged potential violations of processes and regulations but did not cite a specific instance of harm to participants. In an exhaustive examination of 13 HSPH research projects in China, we recognized that there were weaknesses in some of our procedures but no indication of any harm to study subjects. OHRP found that the School’s efforts over the past two years to improve our processes of human subjects review should provide assurance that harms or lapses in observing appropriate procedures will not occur in the future. Additionally, OHRP determined that more recent, anonymous allegations from a complainant in China of fraud in informed consent could not be substantiated.
The research, principally funded by the National Institutes of Health (NIH), consisted of non-invasive health studies—the monitoring of the health of large groups of people--undertaken to gain knowledge about the causes of certain common and lethal diseases such as asthma, preterm birth and hypertension, a risk factor for cardiovascular disease which kills more than 15 million people around the world every year.
One of the most exciting areas of biomedical research seeks to link the genetic or intrinsic risks for illness and the environmental or external risks. For such research it is important to study carefully large numbers of people to detect significant risks in a normal population. China is an ideal site for such research because it has acknowledged environmental problems, highly motivated academic health professionals eager for collaboration and training in the new genetic technologies, and the capacity to carry out very large scale population studies.
Participants gave voluntary, informed consent. They answered questionnaires and may have kept health diaries or had their blood pressure or lung function measured. They gave small blood and/or urine samples and were compensated for their travel expenses and work time missed. Again, these were observational health studies; there were no experimental treatments involved.
Between October 1999 and May 2001, OHRP had posed a series of over 100 questions about the studies, which HSPH investigated and answered exhaustively. In a March 28, 2002 determination letter, OHRP concluded that there were a number of procedural lapses in HSPH's oversight and record keeping but did not find any harm to any of the participants and did not apply any sanctions to the School. Instead, OHRP found satisfactory the School’s corrective actions to its procedural lapses in the named studies and approved a formal "Quality Improvement Plan" created by the School for its overall program of human subjects protections.
The two HSPH researchers involved in the studies, Dr. Xiping Xu and Dr. David Christiani, were reprimanded by the Dean of the School for omissions in fulfilling all the applicable policies and rules for seeking timely review and approval. Both investigators cooperated fully with corrective action plans required by the Dean and the institutional/ethical review board (IRB). Dr. Christiani recently received a new grant from NIH to continue tracking the environmental exposures and health of Chinese factory workers. Dr. Xu’s research, which was suspended by the School pending conclusion of the inquiry, is resuming in phases, beginning with a study of health consequences of pesticide exposure in Chinese farm workers.
HSPH took very seriously the organizational criticisms offered by OHRP concerning staffing for its institutional/ethical review board (IRB), documentation of review procedures, verification of the integrity of consent procedures, and the training and fostering of a culture of awareness about the importance of human subjects protections throughout the School and among its partnering institutions abroad. Changes were needed to strengthen the School's compliance with the evolving and more stringent regulations regarding research subjects.
The School responded constructively to expand its human subjects protection training and oversight, both for HSPH researchers and for collaborating teams in China and other countries where HSPH has projects. It increased staff support and space for its IRB, hired a professional IRB Director, and supported a broad program of quality improvement initiated by the IRB leadership team. The IRB policies and procedures have been thoroughly updated; the website expanded as a service and information tool for researchers; and a novel program of real-time consent monitoring was launched in March 2002. To date, the IRB has conducted site visits for training and consent monitoring in Botswana, Nigeria, Tanzania, China, Kuwait and Boston. The HSPH IRB has also been collaborating with two other Harvard IRBs on sharing best IRB practices, including a joint creation of a new Harvard-wide IRB database, funded in part by an NIH grant. With annual HSPH training requirements for researchers strengthened and enforced, over 2,000 individuals have benefited from this enhanced program since October, 2001.
To answer OHRP’s questions about the 13 research projects, HSPH undertook a major fact-finding inquiry carried out as thoroughly as possible. The school examined computer, telephone, IRB and financial records of the study investigators. An independent inquiry was made by the Brigham Hospital and Harvard Medical School, collaborators in some of the studies. Finally, the head of the School's IRB, Troyen Brennan, who is both a physician and lawyer, made a visit to the China sites to personally examine signed consent forms and interview collaborators and research subjects. The School’s academic dean, James Ware, previously had traveled to China to meet with collaborating partners and inspect the research sites. The HSPH IRB engaged in a very useful series of communications with its Chinese IRB counterparts, culminating in personal meetings between Dr. Brennan and IRB colleagues in Anhui, China, who kindly shared the findings of their independent inquiry into the allegations made. Finally, Dr. Brennan met in Beijing with the leadership of the Human Genetics Resources Administration investigation in 2001, comprised of scientists gathered by the Ministry of Science and Technology, and the Ministry of Health, who kindly shared the findings of their independent investigation of the studies. None of the four independent inquiries was able to substantiate allegations of any harm being done to individual subjects or of fraud in obtaining informed consents. As a consequence of these investigations, regrettably, several projects have irrevocably been set back or discontinued. Nevertheless, it is our intention to renew a smaller number of collaborative projects. In this context, a joint consent-monitoring program in China, supported by both IRBs, is planned for the coming year.
"Harvard is committed to international health research and to mutually beneficial collaborations that help other nations build the capacity to promote good health for their citizens," said Dean Bloom. "We have learned from the OHRP’s China inquiry the complexity of collaborative international studies and have undertaken major efforts to tighten up our oversight and improve our quality assurance of all projects. We recognized that the appropriate procedures were not always carried out as carefully or in as timely a manner as we would have liked, but we are reassured by our investigations, as well as OHRP’s inquiry, that no individual participant had been harmed and no willful violations of human subjects procedures took place."
"We think our current procedures can now serve as a model for human subjects regulations compliance in public health research," he said, "and we look forward to sharing our knowledge and expertise acquired in this area with colleagues here and abroad engaged in similar studies or concerned about best policies and procedures to assure ethical research involving human subjects."
The OHRP’s determination letters can be found at: http://ohrp.osophs.dhhs.gov/detrm_letrs/lindex.htm
"As a result of the above determinations, there should be no need for further involvement of OHRP in this matter."
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