June 14, 2006

The Sale of Tissue Samples from NIH to Pfizer

This is a copy of the full, staff report of the House Energy and Commerce Committee on the sale of spinal cord fluid tissue samples by a scientist at the NIH to Pfizer. It makes for some pretty chilling reading. It also stands as a stark reminder that without more oversight and regulation biobanking is going to face an uphill battle in capturing public trust:
Background ...Given that human tissue samples are increasingly used in translating biomedical discoveries into improved medical care, the issue of human tissue samples has assumed greater importance at the National Institutes of Health (NIH) and strengthened the need for more guidance to NIH-funded institutions (NIH's extramural research program that more than 80% of NIH's budget) as well as for the Institutes and Centers at the NIH that conduct their own research (NIH's intramural research program). The focus of the hearings is the collection, storage, tracking, and use of human tissue samples in the NIH intramural research program.

The Committee's investigation in this area was prompted in part by concerns raised by Susan Molchan, M.D., Program Director for Alzheimer's Disease Research at the National Institute of Aging (NIA), to Committee staff in April 2005. Dr. Molchan had been a clinical researcher interested in Alzheimer's disease research at the National Institute of Mental Health (NIMH). From 1993 to 1995, she conducted a small clinical trial involving the collection of spinal fluid from about 25 people (some patients with Alzheimer's disease and some normal volunteers) and the use of lithium as a probe for potential biomarkers of Alzheimer's disease in spinal fluid and blood. In early 1997, Dr. Molchan left the NIMH, but she had not finished this study. She had published two papers and used at the very most 20% of the spinal fluid collected. The unused spinal fluid remained stored in freezers at the NIMH Geriatric Psychiatry Branch. The Chief of the Geriatric Psychiatry Branch was Trey Sunderland, M.D., who assumed control of the spinal fluid samples after Dr. Molchan left NIMH. At a hearing on June 22, 2004, the Subcommittee on Oversight and Investigations revealed that Dr. Sunderland had received over $500,000 in payments from Pfizer during 1999-2004 for outside consulting and speaking without any record of prior approval for these activities or disclosure in his government financial- report filings.

In the fall of 2004 Dr. Molchan was now at the NIA and was trying to assist an outside researcher in getting unused samples from Dr. Molchan's study at NIMH. Ultimately by March 2005, Dr. Molchan learned that Dr. Sunderland was only able to produce around 2-3% of unused spinal fluid that remained from the lithium study and that the clinical data from that study had been purged. She was concerned about what happened to the more than 95% of the unused spinal fluid samples left in the freezer and to the data. In particular, after learning from public reports about Dr. Sunderland's undisclosed Pfizer activities, she was concerned that Dr. Sunderland might have inappropriately or improperly diverted spinal fluid samples from her lithium study to Pfizer as part of his financial relationship. She pursued her concerns for several weeks during March-April 2005 through various NIH channels and with the Office of Inspector General (OIG), Department of Health and Human Services (HHS). In April 2005 she contacted staff with the Committee on Energy and Commerce.

In investigating her concerns and in general about the relevant NIH policies, the Committee staff learned from NIH officials that NIH had no uniform, centralized, and mandatory authority regulating the handling of human tissue samples. Some NIH laboratories kept a written record on the maintenance of these samples, but other NIH laboratories did not. Although there were explicit regulations defined in 42 C.F.R. 72.6 detailing the handling for hazardous biological materials and select agents, there was no explicit policy for the handling and accounting of human tissue samples. In addition, there was no formal inventory control or tracking system at NIH. If a freezer or other storage facility malfunctions and the human tissue samples become unusable, NIH laboratories were not required to account for the disposition of these samples. There was reason to believe that there were cases where NIH lost human tissue samples but had no record of what had been lost. Moreover, the lack of accountability left NIH wholly vulnerable to theft and diversion of valuable human tissue samples. These preliminary inquiries raised serious concerns over what was described to Committee staff by NIH officials of a fairly loose, ad-hoc approach to controlling human tissue samples.

On June 20, 2005 the bipartisan leadership of the Full Committee and the Subcommittee sent a letter to the Director of the NIH requesting records and information on how human tissue samples are obtained, stored, tracked, and used in intramural programs throughout the institutes and centers of the NIH. One subject area of the Committee's June 20, 2005 request concerned the disposition of spinal fluid samples from patients with Alzheimer's disease and control subjects collected by scientists at the National Institute of Mental Health (NIMH) to be used in studies involving lithium. After the NIH's August 15, 2005 production, the Committee staff alerted the NIH that it appeared that not all responsive documents concerning these samples and Dr. Molchan's lithium study had been provided to the Committee. After the Committee staff raised these concerns with the NIH about the production, the Committee did receive additional responsive records: three sets of records over the last few months from the NIH related to the spinal fluid samples and the lithium study, with the last set received on January 4, 2006. The Committee was troubled that the NIH did not produce all the responsive records in the first production, and produced these records only after Committee staff pressed several times for these additional responsive records.

Most importantly, an NIH document received by the Committee in early 2006 documented that Dr. Sunderland's branch had sent spinal fluid samples to Pfizer from 538 subjects, who had participated in 14 different studies at NIMH. The protocol numbers listed on the documents showed that spinal fluid had been sent to Pfizer from subjects who had participated in Dr. Molchan's lithium study. That fact had not been previously disclosed to either Dr. Molchan or to the Committee.

On January 24, 2006, the bipartisan leadership of the Committee and the Subcommittee sent a letter to NIH requesting additional records about the disposition of the spinal fluid samples, the nature of NIMH oversight over human samples, and the way NIH/NIMH handled the Committee's request for records relating to the lithium study. In addition, on January 24, 2006, the bipartisan leadership of the Committee and the Subcommittee sent a letter to Pfizer, requesting records that could help determine the relationship, if any, between the disposition of the spinal fluid samples in question and Dr. Sunderland's official and/or private consulting activities with Pfizer.

To review these issues related to human tissue samples, the Committee staff conducted extensive interviews with officials from the NIH, former officials with the NIH, officials with Pfizer, former officials with Pfizer, and other individuals. Staff reviewed documents obtained by the Committee from the NIH and Pfizer. Staff also reviewed public information and records.

After several months of work, the Committee staff wrote a staff report summarizing the findings and supporting evidence. The staff report addressed three questions. In brief, the staff report's findings can be summarized as follows:

Question One: Did Dr. Sunderland obtain personal financial benefits from outside activities (with no record of disclosure to NIH or approval by NIH) with Pfizer, Inc., in any way because of actions he took in his official capacity in facilitating the transfer to Pfizer of human spinal-fluid samples and plasma samples, which were the assets and property of NIH?

Finding/Supporting Evidence: Yes. Records and interviews provide reasonable grounds to believe that Dr. Sunderland personally received $285,000 in compensation from Pfizer for activities that were derived directly from his official acts in providing Pfizer access to spinal fluid samples and plasma samples (over 3000 tubes of NIH property and linked clinical data) and that Dr. Sunderland used NIH employees and resources to provide such access.

Question Two: Does the available evidence provide reasonable grounds to believe that Dr. Sunderland and others omitted important information, or provided inaccurate information, about the circumstances surrounding Dr. Sunderland's collaborations with Pfizer, Inc. that involved the human samples provided by Dr. Sunderland?

Finding/Supporting Evidence: Yes. While Dr. Sunderland refused invitations to be interviewed by the Committee, records and interviews provide reasonable grounds to believe that some of Dr. Sunderland's statements to the investigators from the Office of Management Assessment and communications from Dr. Sunderland's attorney to the NIH were factually inaccurate or incomplete, especially statements relating to the nature of the Pfizer collaborations involving human tissue samples.

Question Three: Did the Committee's investigation of the circumstances surrounding Dr. Sunderland's transfer of human samples to Pfizer identify evidence that raised other compliance issues and policy questions?

Finding/ Supporting Evidence: Yes. The investigation found reasonable grounds to believe there was questionable compliance with human subject protection and NIH technology transfer policies that existed at the time. The evidence also raised regulatory and ethical questions that are pertinent to NIH's consideration of current policy related to human tissue samples.

Detailed discussion of the supporting evidence and issues raised are covered in the staff report.

-Arthur Caplan

View blog reactions

| More