Beth Clay: An Insider Looks at Nicholas Gonzalez ' New Book on the NIH's Clinical Trial of His Pancreatic Cancer Care

Summary: The Gonzalez cancer treatment was well known in the alternative medicine community long before the NIH NCCAM and the National Cancer Institute decided to fund a trial on his treatment of pancreatic cancer. The news of the trail was huge: a giant from outside the system was to be explored in a major trail by researchers deep inside the system in a moment when trust between the two communities was about as palpable as that between the US and the USSR in the middle Reagan years. Not surprisingly, the trial proved controversial. Here a Gonzalez associate, former NIH and US Congress staffer Beth Clay on Gonzalez book What Went Wrong: The Truth Behind the Clinical Trial of the Enzyme Treatment of Cancer.

New book on a controversial trial

Beltway consultant Beth Clay has multiple connections to her subject matter in this review of What Went Wrong? Nicholas Gonzalez, MD's new book. She was a founding staff of the NIH office that subsequently funded the work. As a staffer subsequently on the House Government Oversight Committee, Clay is experienced in major investigations. As a committed part of the movement for more choice in integrative care, she is aware that history is replete with examples of conventional medicine throwing up barriers to choice. As a Beltway professional, Clay has worked with Gonzalez to help him respond to the outcomes of the controversial

Reviewer Beth Clay

In the fall of 2009, I reported via the Integrator Blog my concerns about the management of the first ever direct comparison of an alternative and conventional approach to treating pancreatic cancer funded by the National Institutes of Health (NIH).  Both the National Cancer Institute (NCI) and the National Center for Complementary and Alternative Medicine (NCCAM) were involved in funding and managing the study. With a decision to evaluate the Gonzalez protocol came a determination by the NIH staff that a conventional researcher at an academic center needed to act as principal investigator for the study, presumably to insure the study was well run.  John Chabot, MD, at Columbia University Medical Center became the principal investigator.     

At the time, I shared with the Integrator Blog the following comment:  "The last decade as far as the general public and the alternative medicine community knew was devoted to the rigorous management of what might have been the most important pancreatic cancer study of the century. Instead what took place was a series of management failures by at the NIH both at NCI and NCCAM. Further, there were serious violations of the research protocol (including mismatching the arms of the study and then retrospectively re-staging them in an attempt to equalize them) and failure to insure human subject protections by the principal investigator; attempts at the NIH to brush the violations and mismanagement under the rug either through malfeasance or incompetence; and a government investigation that confirmed that Dr. Chabot failed two thirds of the time to provide adequate informed consent to patients. And finally, a failed and then successful attempt by Dr. Chabot to publish a fraudulent research paper." 

Gonzalez: getting his story out

The history of this project is one I know well.  I have the unique history of having worked in the complementary and alternative medicine (CAM) activity at the National Institutes of Health (NIH), going on to lead health oversight activities for a US Congressional Committee in which CAM was a focus and continuing involvement in the field now that I am in the private sector.  As a matter of disclosure I have consulted with Dr. Gonzalez for a number of years and know the accuracy of the information provided within the book. 

"Few in the CAM community have been willing to wake up and enter into the fray of discussing an egregious miscarriage of justice for the pancreatic cancer community and for the future of honest dialogue about CAM research."

Reading What Went Wrong reminded me of the statement - the less the people know about how sausages and laws are made, the better they sleep in the night. One need only exchange the words "laws" with "CAM research" to understand my perspective.  To date, few in the CAM community have been willing to wake up and enter into the fray of discussing an egregious miscarriage of justice for the pancreatic cancer community and for the future of honest dialogue about CAM research. To quote Dr. Briggs' comment to Dr. Gonzalez, most want to ‘look forward' not backward. However, if we do not learn from our history, we are destined to repeat the mistakes of the past.  One has but to think of the Tuskegee Syphilis study to appreciate why we must understand when research studies go off track.

What Went Wrong is the first person accounting by Dr. Nicholas Gonzalez of the Clinical Trial NCT 00003851 (Project Number:  P30-CA1369) entitled "Gemcitabine Compared With Pancreatic Enzyme Therapy Plus Specialized Diet (Gonzalez Regimen) in Treating Patients Who Have Stage II, Stage III, or Stage IV Pancreatic Cancer."  This is the author's third book; the first two being One Man Alone: An Investigation of Nutrition, Cancer, and William Donald Kelley and The Trophoblast and the Origins of Cancer: One solution to the medical enigma of our times. He also wrote a foreword for the reprinting of The Enzyme Treatment of Cancer and Its Scientific Basis by John Beard D.Sc.
 
What Went Wrong  provides two forewords, the first from 11 year pancreatic cancer survivor Sarah Ann Cooper who attempted to enter the trial, but was rejected and opted to be treated by Dr. Gonzalez and Dr. Isaacs off trial. (She was rejected by Dr. Chabot because she refused Whipple surgery.)  The second foreword is from Paul Rosch, MD, President of the American Institute of Stress; a name familiar to many in the CAM community.  His informed observations develop into critical questions that the community would be well served to address.

"This is not the story of a single error in management of the study, but a series of violations of protocol, ethics, and law."

Dr. Gonzalez opens the book by providing the historical background and a summary of the major problems that developed with the study.  While What Went Wrong is a long read (more than 500 pages), it is organized in logical fashion and separated into 44 chapters.  As one learns in this book, this is not the story of a single error in management of the study, but a series of violations of protocol, ethics, and law.  That these occurred at a prestigious academic institution under federal supervision is particularly disturbing.  Why it was not on the front page of the New York Times that an NIH funded study investigator (Dr. Chabot) was found by the Food and Drug Administration (FDA) to have (1) Inadequate informed consent form, (2) Failure to follow investigational plan, (3) Inadequate and inaccurate records, and (4) Failure to list additional investigators on 1572 (Statement of Investigator) is also disturbing.  Had it been Dr. Gonzalez that committed these violations along with changing the treatment protocol (from Gemcitabine alone to a three drug combination that Columbia was developing) and retrospectively restaging the patients in the two arms of the study in an attempt to correct the mis-matching of the two arms, one can be assured it would have been a leading story and that the NIH/NCI/NCCAM would have issued a press release condemning the acts and banning him from receiving research grants in the future.

While the book is well documented, providing excerpts from letters and emails that document every facet Dr. Gonzalez' concerns, in retrospect, "Chapter 10 Payment Delays" does not fully detail the significant issue the failure for the grant funds to be provided became.  Readers I believe will be shocked to realize that due to mismanagement of the financial aspects of the grant, there was a period of 8 months in which Dr. Gonzalez was forced to pay for the nutrition arm of the study out of his own pocket. I remember well this issue as I was working for Congress and was asked to help.  Inquiries we made to expedite a resolution were frustrating and showed apathy and mediocrity.  While this was Dr. Gonzalez's first foray into NIH funded research, Columbia University in 1999 had more than 1,100 grants with the NIH and presumably would understand how to receive payment so that studies could be funded on time.  Furthermore between 1999 and 2012, Columbia received 50 pancreatic cancer related grants from the NIH totaling more than $10 million.  That patient's lives were literally at stake seemed to be lost in the bureaucratic paper shuffle and blame game.  How often has a cancer researcher had to pay for clinical trial treatments out of pocket while waiting for the NIH and academic administrators to do their jobs?  

	"There was a period of 8 months in which Dr. Gonzalez was forced to pay for the nutrition arm of the study out of his own pocket. I remember well this issue as I was working for Congress and was asked to help."

Having conducted a number of Congressional oversight investigations, I am well familiar that mismanagement issues are seldom isolated and often have far reaching consequences.  In Chapter 25, Dr. Gonzalez details another NIH-funded study (the now infamous HIV-Nevirapine clinical trial) that was mismanaged and draws a connection to the NCI/NCCAM study. 

Chapters 41 and 44 may be the most important chapters of the book as they take the reader through the actual study data and the Chabot publication.  This section also details how Sarah Ann Cooper was rejected from the study and challenges Dr. Chabot's interpretation of the data.

Since the creation of an alternative medicine research activity at the NIH two decades ago, we as a community have discussed how to effectively conduct research to evaluate CAM protocols, in dozens of meetings discussing how or if to conduct randomized controlled trials, outcomes studies and how to build an evidence-base using multiple types of studies.  Taxpayers have provided more than $1 billion in research funds. While this study represents one tenth of one percent of that money, it was the first and likely the only head to head comparison of an alternative cancer therapy and the conventional approach.   

"This is an essential read for everyone interested in CAM research.  I believe it is a must read for the NCCAM advisory board members past and present."

This is an essential read for everyone interested in CAM research.  I believe it is a must read for the NCCAM advisory board members past and present.  I have found no evidence that the NCCAM briefed the Advisory Committee on the study, or the various regulatory oversight investigations that took place and found violations. Nor have they invited Dr. Gonzalez to present at an advisory board meeting. 

To compound this, after this book went to press, a response from the NCI/NIH to a Data Quality Assurance Act included the following:  "...evidence is lacking that administrative deficiencies identified in the Gonzalez Regimen trial by OHRP and the FDA materially affected other activities of the trial or the reported findings."  It is illogical to believe that an FDA finding of inadequate and inaccurate record keeping does not ‘materially affect' the research findings. This book provides all the evidence the NIH needs to validate the OHRP and FDA findings, to correct the public record and call for a retraction of the Chabot article.

Dr. Gonzalez has done a thorough and accurate job of documenting this decade long endeavor.     

What Went Wrong: The Truth Behind the Clinical Trial of the Enzyme Treatment of Cancer by Nicholas J. Gonzalez, MD is available through New Spring Press (www.newspringpress.com) ISBN: 978-0-9821965-3-3  ($39.95)