- Contact the Committee

ANSWERS TO QUESTIONS  --  FRANKLIN J. ZIEVE 

QUESTION #1 – Dr. Zieve, you mentioned that your annual “Research Day” includes an opportunity for veterans to voice concerns or complaints they may have about VA research and their participation.  Please provide additional information on the types of concerns or complaints occasioned at these Research Day events. 

(1)         Problems after study terminates (by far the commonest complaint, but generally minor)

· Can’t continue study drug after study is over.

· No weekly/monthly clinic visits after study is over.

· Get charged for medications when study is over.

· Must deal with waiting times and scheduling hassles in regular clinics.

· Want to be contacted if a new treatment for their condition seems promising.

(2)         Problems during study

·  When they signed up they did not realize the time commitment required of a study participant.

·  Would like to interact more with study doctor.

·  When asked if they understood their consent form, several subjects said it was complicated but they “trusted their doctor to take care of them.”  This feedback has led our IRB to insist on simpler consent forms, while pressure from both VA and external sponsors is consistently in the opposite direction (they want to create a legal document to protect themselves rather than something the volunteer can understand).

· One veteran complained about being charged for medication to treat a study side effect (his upset stomach).  We contacted the investigator, who reviewed the subject’s case and deemed that due to side effects it was in the patient’s best interest to discontinue participation.

(3)         Problems in recruitment

· The commonest study-related problem was exclusion from a study – “my friend got to participate in a hip study but I was never asked.”  Equity of recruitment is a more important issue than we had appreciated, and we have started addressing it formally at the time of IRB review. 

QUESTION #2 – I’d like to quote a portion of your written statement:  “Over 95% of the funds which flowed into McGuire Research Institute in its first years replaced funds kept at the affiliated medical school.  Virginia Commonwealth University (“VCU”).  When this movement of funds to MRI started, we found some research studies which had been going on at McGuire without any VA knowledge.  The money was at VCU; the drugs were dispensed from the VCU pharmacy, brought to the VA in paper bags and administered to our patients without any record in their VA charts.” 

Could you please elaborate on this and explain what kind of research was “conducted without any VA knowledge?”  What actions were taken to address the drug dispensing procedure? 

The short answer to this question is that we developed our Human Research Protection Program, involving MRI, our IRB, our Investigational Pharmacy, and our training program.  The overall process took 10 years (which seems amazing in hindsight, but is consistent with the primitive state of human subject protection in 1990) and is continuing.  Here was the sequence: 

(1)         The Funding.  At first virtually all the funds for VA clinical studies were kept at our affiliate, VCU, and we used the VCU IRB.  We did not have the resources to fund a separate Investigational Pharmacy, so investigational drugs were kept in our hospital pharmacy, which provided poor service and poor record keeping.  After MRI was established we got our first look at the funds associated with clinical research at McGuire VAMC; it was obvious that the number of patients in studies at McGuire was far larger than we had realized.  Some VA investigators had large projects which we had thought were small, and some VCU investigators had no approved projects at all, but still wanted to put funds in MRI.  The ongoing unapproved studies ran the spectrum from questionnaires to drug studies.  Since all of these studies had approval of the VCU IRB, which we used, we simply asked the investigators to submit them to the R&D Committee.  When non-VA employees were being used, they were sent to apply for WOC appointments.  We only shut down a handful of projects.  We instructed all investigators to use the VA Pharmacy for investigational drugs, but at that stage we could not easily get information to enforce this.

(2)         The IRB.  As we became more sophisticated we were dissatisfied with the VCU IRB, but we were not politically able to set up our own until 1999.  With our own IRB, and with the VCU shutdown, we found a few more studies by VCU investigators which used VA patients, giving them investigational drugs from the VCU pharmacy, but had never been through R&D Committee approval.  These studies were shut down promptly.

(3)         The Investigational Pharmacy.  Our Investigational Pharmacy was established for the sole purposes of handling all study drugs at McGuire VAMC and of enforcing all human subject regulations.  For the first time we felt we had adequate control:  no patient is issued a study drug until a signed consent form is in the Investigational Pharmacy and a clinical warning is on the cover sheet of the electronic patient record.  The pharmacy data provides an important base for the IRB’s continuing review of each project.

(4)         The Training Program.  We have invested over $50,000 to train all personnel associated with human research at McGuire VAMC (e.g. we currently have 20 Certified Clinical Research Coordinators).  This cadre of trained people provides an additional safeguard – if someone brought in a drug in a paper bag today, someone would be likely to notice him and take action.  We feel this is an important additional protection.

In summary, control of human research at a VAMC requires control of the money, the IRB, the drugs, and the personnel.  The multiple layers of protection are important; if you only have one tollkeeper, someone can always find a back road to get around him. 

QUESTION #3 – You are an advocate for continuation of the research foundations.  Do you have any recommendation for improving their functions, based on your experience leading the McGuire Research Institute? 

(1)         What good are they doing for the VAMC?

·  The corporations’ fundamental underlying function is to support and improve the VA Medical Center by providing a flexible funding mechanism for the acquisition and administration of additional research resources.  However, the annual reporting requirements of corporations do not include evaluation of what they have done to support either the medical care or the research appropriations of the hospital.

·  I suggest that each corporation should make an annual report on what it has done to support the hospital (signed by the Medical Center Director) and to support the VA-appropriated research program (signed by the ACOS/R&D).  Specific dollar figures and FTE should be specified.  This should be part of the corporate annual report to VACO, and it should be reviewed both locally and centrally.

·  It is possible to run a VANRC so its effects on the hospital are either major or inconsequential.  Our operating and auditing standards should be able to tell the difference, but currently they don’t address this point.  Changing this is a simple way to increase VA’s benefit from the corporations.

(2)         Corporations need feedback on their annual reports.

·  When Richmond assembled the annual reports from VANRCs, we gave a “public flogging” report each year at the NAVREF meeting.  Our reports, which were noted in the 1997 OIG report on the corporations, highlighted questionable practices and specific items subject to improvement. 

·  More recently, the annual reports have gone to the VACO collection point, but there has been no feedback to the sites.  If the annual reports are to be used as an instrument to improve the corporations, somebody should read them, and each station should get feedback.

(3)         Corporations should fund the Human Research Protection Program (HRPP).

· Nationwide, most VA human research is administered through VANRCs.  Human research protection is a front-burner issue right now, the standard of practice is changing rapidly, and most VAMCs are seriously behind in achieving compliance; if they wait three years for VACO to figure out what to do they will risk a public relations fiasco and, more importantly, inadequate protection of veterans.  The corporations should fund the HRPP now.  It is in their best interest, in VA’s best interest and most importantly in veteran’s best interest for the corporations to take charge of providing for human subject safety in VA research.  The issue is too important to wait.

(4)         Corporations should develop “rainy day” reserves.

· For its first 10 years McGuire Research Institute was was run on a shoestring so as to accumulate a significant reserve for a rainy day.  When the rainstorm came in 1999, we were quickly able to spend an additional $500,000 per year on our human research protection program.  If we had not had a substantial reserve, we would have been shut down.

· Most VANRCs are run by career federal employees who are used to spending their entire budget each year.  A corporation can help its VAMC most by systematically assembling reserves and preparing to act quickly.  This is the most powerful tool the corporation has.

(5)         Corporations should be run for the long term.

· VANRCs should develop a “foundation” mentality:  build net assets and fund initiatives off the interest rather than the principal.  Create an enduring VA research enterprise; don’t just live for today. 

QUESTION #4 – Based on the testimonies you heard at our hearing, what recommendations would you offer the Committees in enhancing the monitoring of the activities of the research foundations? 

(1)         Better use of the independent auditors

· Every VANRC with > $300,000 in revenues must be audited annually by an independent auditor.  As a result there is a low probability of fraud and embezzlement.  It is reasonable to assume that VANRCs are functioning according to generally accepted business practices.  MRI’s 2001 audit cost $17,291, and it was far more thorough and inclusive than any audit we have undergone by VA-related entities.

· Despite the effort and expense which goes into the audits, the independent auditors have never been given any direction whatsoever by any VA-related entity.  Thus, the audits have never asked a VA-specific question, but have been concerned only with observance of standard good business practice.

· The simplest way to enhance monitoring of corporate activities would be for VHA, OIG, or the Committees to give VA-specific auditing criteria or questions for the independent auditors to address.  I can think of some obvious areas to look at, but the important thing is the principle that the annual audit could look for compliance, not only with GAAP, but also with the VA Manual.

(2)         Evaluation of what corporations directly do for the VAMC (see above)

· Ultimately the corporations exist to support the overall VHA health care enterprise, but I am not aware of any oversight which has addressed the impact of the corporations on the VAMCs.  If they are not helping the medical centers, there is little reason for them to exist.  In addition to looking for specific actions which are questionable, the oversight should try to assure that the corporations are doing big things that are good.

(3)         Better review of the assembled annual reports

· When Richmond was responsible for collating the corporate annual reports, we noted some corporations which could potentially have been heading for financial trouble (e.g. corporations whose revenues consisted of a very small number of large grants, but whose administrative structure was based on the assumption that these would continue indefinitely).  While no disasters have occurred thus far, it would be worthwhile to reduce their chances of occurring in the future.  This would require a truly knowledgeable review group for the annual reports.  It cannot be done by VACO – nobody in ORD could run a corporation from VACO if his life depended on it!  On the other hand, it cannot be done by NAVREF, an advocacy organization.  My suggestion is to appoint a group consisting of 2-3 very experienced VANRC executive directors, one ORD representative, and one private sector auditor to review the annual reports and give feedback to VACO and to the corporations. 

A Final Thought.  There are a few simple, fundamental questions which we ask all the time when we are considering whether MRI should move in a new direction:

·        Is it good for the hospital?

·        Is it good for the patients?

·        Is it good for our professional role as physicians?

This is the thinking I consider most important if the corporations are to live up to their potential.