On an almost daily basis, there are news stories sharing with the public the‘latest’ research findings. Everything from whether wine, meat, or bread are good for you; where you should take a multivitamin,to the latest findings on drugs and devices being developed to diagnose and treat cancer, diabetes, and a myriad of other conditions. There are threeissues about which I have increasing concerns:
- Researchers who fail to disclosefinancial conflicts of interest in scientific publications or media interviews;
- Industry-government collaborationsand research outcomes; and
- Treating all researchoutcomes as equal in media discussions.
A National Institutes of Health (NIH) online training module on research integrity provides, “The scientific community and the community at large rightly expect adherence to exemplary standards of intellectual honesty in the formation, conduct, reviewing, and reporting of scientific research.” (1) If the integrity of the scientific process breaks through a failure of those involved to adhere to the highest standards of intellectual honesty then our annual $30 billion-plus investment in research at the NIH is wasted because the public will not be able to trust the outcomes. The same can be said at the Centers for Disease Control and Prevention (CDC)and other federal research and regulatory organizations. In the early 1990s, I received some of the best training one can from an NIH manager responsible for training committee Management Officers. She was a stickler for the rules and with good reason. At the NIH, the Institute or Center advisory committees are responsible for a final phase of reviewing and approving research grants for funding (thefinal decision is the Institute or Center Directors). These individuals aregiven access to confidential research information which eventually might resultin patents. They are also oftenresponsible giving feedback on the direction research funding will befocused. Those who serve on advisoryboards go through an extensive financial disclosure process. If the advisor has stock holdings, researchgrants, or consulting relationships with corporations or other potentially conflictedorganizations, this is supposed to be disclosed and consideration on whether theindividual can participate in closed door sessions where grant applications arereviewed and discussed is determined. Aconflict of interest waiver process exists and public disclosure during themeeting is supposed to occur. Otherfederal agencies have the same process as it is directed in part through theFederal Advisory Committee Act (FACA). Atthe Food and Drug Administration (FDA) their advisory bodies weigh in not ongrant funding, but on product approval. The outcomes of the vote of an FDA advisory committee can mean tens ofmillions of dollars made (or lost) by a company.
The vast majority of those who work within our federal health agencies I believe are good people. I have met some who were passionate about public service, some who were mediocre at best, and others that were simply showing up each day. I have also met a few that the word scoundrel is a polite descriptor. There are many unsung heroes at the NIH who have changed our lives for the better by being dedicated public servants. One of those people, for instance, is Dr.Stephen Groft, now retired director of the Office of Rare DiseasesResearch. I first met him when he was helping bring together five federal agencies to create a Biodiversity program to be managed by the NIH’s Fogarty International Center in the early 1990s. The Biodiversity program was established to address the interdependence of biodiversity exploration for potential applications in health, with investments in research capacity that support sustainable use of these resources, the knowledge to conserve them, and equitable partnership frameworks among research organizations in the U.S. and low- and middle-income countries (LMICs), as defined by the World Bank. I was able to observe Dr. Groft at this time show great patience and professionalism in negotiating the terms of the project with agencies with competing interests and see the program launched. Today, a quarter century later, the program continues. I had no idea at the time, the integral role Dr. Groft played in the Orphan Products Drug Act. He was so adept at managing challenging situations that NIH and HHS leadership frequently called upon him to manage difficult tasks. These included being the first acting director of the Office of Alternative Medicine (the Congressionally mandated, predecessor organization to the National Center for Complementary and Integrative Health); and serving as Executive Secretary of the White House Commission of Complementary and Alternative Medicine Policy, also mandated by Congress. I had the honor and privilege of working with him for a couple years before leaving the NIH to work for Congress. All these years later, I have never met anyone with more integrity, compassion, patience, and dedication to the public good than Dr. Groft. (2,3)
It is because I know there are good people within the agencies, that I believe we each have a role in helping fix the growing problems, to work together to shoreup the foundations of scientific integrity before they crumble. Shinning thelight of day on these issues is a first step to identify issues and worktowards solutions.
The NIH Mission is: “to seek fundamental knowledge about the nature and behavior of living systems and to apply that knowledgeto enhance health, lengthen life, and reduce illness and disability.” (4)
The Food and Drug Administration’s (FDA)Mission is: “Protecting consumers and enhancing public health by maximizingcompliance of FDA regulated products and minimizing risk associated with thoseproducts. (5)
The Centers for Disease Control and Prevention(CDC)’s Mission is: “CDC works 24/7 to protect America from health, safety and security threats, both foreign and in the U.S.Whether diseases start at home or abroad, are chronic or acute, curable or preventable, human error or deliberate attack, CDC fights disease and supports communities and citizens to do the same. CDC increases the health security of our nation. As the nation’s health protection agency, CDC saves lives and protects people from health threats. To accomplish our mission, CDC conducts critical science and provides health information that protects our nation against expensive and dangerous health threat and responds when these arise.”
In
addition to their Mission, the CDC now has a Pledge to the
American People
- Be a diligent steward of the funds entrusted to our agency
- Provide an environment for intellectual and personal growth and integrity
- Base all public health decisions on the highest quality scientific data that is derived openly and objectively
- Place the benefits to society above the benefits to our institution
- Treat all persons with dignity, honesty, and respect (6)
I have included these mission statements because I want
to reiterate the specific roles of each agency. It is a reminder to all what where
personnel in each agency should be focused.
Concern 1a: Conflicts
of Interest in Research: I am not alone
in my concern about conflicts of interest in research.
A Hastings Center report included the
following:
- A 1999 study of the Association of University Technology Managers found that 68% of academic research institutions held equity in companies thatin turn sponsored research at the institution.
- A Journal of the American Medical Association (JAMA) 2003 review reported on studies suggesting that about 1 in 4 academic investigators received industry funding for research, a third had personal financial ties with industry sponsors and 40% had accepted research-related gifts.
- The 2003 JAMA paper also found “strong and consistent evidence” that industry-sponsored research tends to draw conclusions favoring industry, often uses an inactive control, and sometimes administers a higher dose of the sponsor’s drug than of the comparison drugs or uses comparison drugs that are poorly absorbed. Industry sponsorship of research, as well as involvement with start-up companies and other commercial relationships, were significantly associated with delaying publication or withholding data.
- 60 percent of respondents in a 2007 survey published in JAMA had personal relationships with industry.
- The death of Jesse Gelsinger died in a gene transfer study at the University of Pennsylvania in1999, conflicts of interest were among the allegations leveled at the research team and the university. The lead investigator and university held equity stakes in a company with a financial interest in the experiment, and the lead investigator and medical school dean held patents on processes used in the trial.
- Rezulin, touted as a type-II diabetes wonder drug was fast-tracked for approval in 1997. The FDA dragged its feet in calling for its removal from the marketplace three years later even with 90 cases of liver failure reported. More than half of the scientists involved in testing Rezulin had received funding or other compensation from Parke-Davis/Warner-Lambert, its manufacturer.
- The Los Angeles Times published a series of articles between 2004 and 2005 revealing that some NIH staff collected significant funds from companies whose products were the subject of NIH research and that the NIH failed to inform the patients involved in the studies. As a result, the NIH’sobjectivity was called into question. The paper reported that this was possible in part because of a relaxing of the rules by then Director Harold Varmus.
- An FDA advisory board voted in 2005 to approve the painkiller Bextra, Celebrex, and Vioxx staying in the marketplace even after being informed of the data showing an increased risk of heart attacks. After the vote, it was made public that 10 of the 32 panel members had been recent consultants to the companies that manufacturedthese drugs. Had the conflict been known, and these individuals notparticipated in the discussion and vote, the outcome may have been different.(7)
In 2009, the National Academy of Sciences took on the topic under contracts with the NIH, the Robert Wood Johnson Foundation, the Greenwall Foundation, the ABIM Foundation of the Josiah Macy, Jr. Foundation, the Burroughs Wellcome Fund, and an endowment fund of the Institute of Medicine. The report opens with an admission that stories on conflicts of interest had become prevalent enough to be broadcast almost weekly. The NationalAcademy report stated, “Patients and the public benefit when physicians and researchers collaborate with pharmaceutical, medical device, and biotechnology companies to develop products that benefit individual and public health. At the same time, concerns are growing that wide-ranging financial ties to industry may unduly influence professional judgments involving the primary interests and goals of medicine. Such conflicts of interest threaten the integrity of scientific investigations, the objectivity of professional education, the quality of patient care, and thepublic’s trust in medicine.”(8)
During the June 15, 2000, House GovernmentReform and Oversight Committee hearing discussing our investigation on advisory committee’s conflicts of interest, after explaining the nature of our investigation (reviewing conflicts in two advisory bodies during the Rotavirus approval timeframe), Chairman Burton’s opening statement included the following:
“Families need to have confidence that the vaccines that their children take are safe, effective and very necessary. Doctors need to feel confident that when the FDA licenses a drug, that it’s really safe and that the pharmaceutical industry has not influenced the decision-making process. Doctors place trust in the FDA and assume that if the FDA has licensed a drug, it’s safe for use. Has that trust been violated? How confident in the safety and need of specific vaccines would doctors and parents be if they learned the following:
- One, that members, including the chair of the FDA and CDC advisory committees who make these decisions, own stock in drug companies that make the vaccines.
- Two, that individuals on both advisory committees own patents for vaccines under consideration, or affected by the decisions of the committees.
- Three, that three out of the five of the members of the FDA’s advisory committee who voted for the rotavirus vaccine had conflicts of interest that were waived.
- Four, that 7 individuals of the 15-member FDA advisory committee were not present at the meeting. Two others were excluded from the vote, and the remaining five were joined by five temporary voting members who all voted to license the product.
- Five, that the CDC grants conflict of interest waivers to every member of their advisory committee a year at a time and allows full participation in the discussions leading up to a vote by every member, whether they have a financial stake in the decision or not. So they’rediscussing it, influencing other members possibly, whether they have a financial stake or not.
- Sixth, that the CDC’s advisory committee has no public members, no parents have a vote in whether or not a vaccine belongs on the childhood immunization schedule. The FDA’s committee only has one public member. These are just a few of the problems we found.
Specific
examples of this include:
- Dr.John Modlin. He served for 4 years on the CDC advisory committee and became the chair in February 1998. He participated in the FDA’s committee as well. He owns stock in Merck, one of the largest manufacturers of the vaccine, valued at$26,000. He also serves on Merck’s immunization advisory board. Dr. Modlin was the chairman of the rotavirus working group. He voted yes on eight different matters pertaining to the ACIP’srotavirus statement, including recommending for routine use and for inclusion in the Vaccines for Children program. It was not until this past year that Dr.Modlin decided to divest himself of his vaccine manufacturer stock.
- At our April 6th autism hearing, Dr. Paul Offit disclosed that he holds a patent on a rotavirus vaccine and receives grant money from Merck to develop this vaccine. He also disclosed that he is paid by the pharmaceutical industry to travel around the country and teach doctors that vaccines are safe. Dr. Offitis a member of the CDC’s advisory committee and voted on three rotavirus issues, including making the recommendation of adding the rotavirus vaccine to the Vaccines for Children program.
- Dr. Patricia Ferrieri, during her tenure as chair of the FDA’s advisory committee, owned stock in Merck valued at about $20,000 and was granted a full waiver.
- Dr.Neal Halsey, who serves as a liaison member to the CDC committee on behalf of the American Association of Pediatrics, and is a consultant to the FDA’s committee, has extensive ties to the pharmaceutical industry, including having solicited and received startup funds from industry for his Vaccine Center. As a liaison member to the CDC committee, Dr. Halsey is there to represent the opinions of the organizations he represents but was found in the transcripts to be offering his personal opinion.
- Dr.Harry Greenberg, who serves as chair of the FDA committee, owns $120,000 of stock in Aviron, a vaccine manufacturer. He also is a paid member of the board of advisors of Chiron, another vaccine manufacturer, and owns $40,000 of stock. This stock ownership was deemed not to be a conflict, and a waiver was granted. To the FDA’s credit, he was excluded from the rotavirus discussion, because he holds the patent on the Rotashield vaccine.
How confident can we be in the process when we learned that most of the work of the CDC advisory committee is done in ‘‘working groups’’ that meet behind closed doors, out of the public eye? Members who can’t vote in the full committee because of conflicts of interest are allowed to work on the same issues in working groups, and there is no public scrutiny. I was appalled to learn that at least 6 of the 10 individuals who participated in the working group for the rotavirus vaccine had financial ties to pharmaceuticalcompanies developing rotavirus vaccines.
How confident can we be in the recommendations for the Food and Drug Administration when the chairman and other individuals on their advisory committee own stock in major manufacturers of vaccines? How confident can we be in a system when the agency seems to feel that the number of experts is so few around the country that everyone has a conflict and thus waivers must be granted? It almost appears that there is an “old boy’s network’’ of vaccine advisors that rotate between the CDC and FDA, at times serving simultaneously. Some of these individuals served for more than 4 years. We found one instance where an individual served for 16 years continuously on the CDC committee. With over 700,000 physicians in this country, how can one person be so indispensable that they stay on a committee for 16 years?”
18 Years Later It Has Not Gotten Better: The NewYork Times reported this month about the failure of very prominent physicians to report in research publications their industry ties. The article reports, “Dr. Howard A. “Skip” Burris III, the president-elect of the American Society of Clinical Oncology, for instance, declared that he had no conflicts of interest in more than 50journal articles in recent years, including in the prestigious New EnglandJournal of Medicine. However, drug companies have paid his employer nearly$114,000 for consulting and speaking and nearly $8 million for his research during the period for which disclosure was required. His omissions extended to the Journal of Clinical Oncology, which is published by the group he will lead.” The investigation also stated a Dr.Robert J. Alpern, dean at the Yale School of Medicine and dozens of others had also failed to report their conflicts. Dr. José Baselga, was forced to resign as chief medical officer of Memorial Sloan Kettering Cancer Center in New York, after it was reported that he failed to disclose industry ties in journal articles. (13, 14) I have done my own reviews of disclosures in research papers and found great inconsistencies in how financial disclosures and conflicts of interest are detailed in research papers. Journals have a role to play in establishing a standard industry-wide and requiring conformity. Federal grant managers also have a role to play in assuring that authors of studies from federally funded research accurately document their funding sources and competing interests or industry ties.
Concern 1b: Undisclosed Conflicts of Interest by Doctors in the Media: With the publication of medical research, or reports about a medical product, media outlets have a Rolodex of medical doctors they often turn to for tv interviews (or for quotes in print media). A few years ago, I conducted an interview with a doctor who had been quoted in the national print press with the intent of writing a paper on the issue of doctors in the media. Time constraints prevented my moving forward with that article, however, I remember vividly this doctor explaining that he gave speeches on behalf more than a dozen different pharmaceutical companies. This information had not been disclosed in the media story and would have been shown his opinion to likely be influenced against the product he discussed by his ties to the pharmaceutical industry. The doctor rather indignantly explained he did not need to disclose his activity because the slide shows he was using were “FDA Approved”. At that point in my interview, I just had to laugh (FDA to my knowledge does not pre-approve pharmaceutical company slide shows used to market their products to the doctors.).
There are a number of doctors who become regular media spokespersons. For instance, you can always count on any story dealing with vaccines to see Dr. Paul Offit interviewed. What is not included typically in his interviews is a disclosure that he was a patent holder (until it was sold); that he is a consultant to one or more drug companies, and that his academic salary is in essence is paid by an endowment provided by Merck. Dr. Stanley Plotkin confirmed during a deposition in early 2018 that he had not included in his curriculum vitae his industry consulting, and according to the CMS doctor payment tracking database from 2013 to 2017 he has accepted over $100,000 in industry funds each year. His deposition confirms he has been taking industry money most if not all his career. In reviewing his media quotes over recent years, there is no disclosure of his financial ties pharmaceutical companies which include Sanofi, Merck, and Glaxo. Another search on the CMS database found that Dr. Jacqueline Wolf, a professor from Ohio University, who is quoted in a 2018article on drugs during pregnancy received payments above the national mean in 2017 from industry.
The public
should be fully informed when a doctor whose being used by the media to offer
their ‘expert’ opinion for or against a product has financial ties to the drug
industry so they can determine for themselves how to receive that opinion.
Concern 2: Industry-Government Collaborations and Research Outcomes
The case of Rezulin: When the Rezulin story broke, I was leading the Oversight inquiry on conflicts of interest and met with staff from the FDA. We asked why it took so long to get the drug out of the marketplace. Their excuse was that Rezulin was such a good drug- the greatest thing the diabetes community had seen in a long time – that they were reluctant to have it withdrawn. Many people died from liver failure because the FDA was slow moving. At the time, the compounding factor that came to light was that Dr. Richard C. Eastman, head of the NIH’s diabetes division was overseeing the Rezulin research and requested an outside activity clearance to become a paid consultant in late 1995 to Warner-Lambert. He claimed at the time that he had been granted outside activity clearance and received almost $80,000 over two years as a consultant and may have received another quarter million from other outside sources. I was told at the time that the NIH had rejected his request for outside activity, but that his supervisor failed to inform him of this and he went forward with an assumption that it was approved. The process requires confirmation of approval, so both the supervisor and Dr. Eastman failed to follow through correctly. This breakdown in the process cost dozens of lives.
There was a time when the NIH held itself out to be a truly independent and free from commercial influence. In fact, President Reagan’s Secretary of Health, Margaret Heckler described the NIH as “an island of objective and pristineresearch, untainted by the influences of commercialization.”
I doubt that Secretary Heckler could have imagined a time when Congress would direct federal officials to engage more intimately with corporations. That is exactly what happened with the passage of the 21st Century Cures Act. We have been hearing about how much better the drug development process is going to improve because of this expanded collaboration. I have grave concerns because government officials are just as vulnerable to industry influence when their interactions are increased as academia are. The evidence is growing to support this concern. After all, he who holds the cash, holds the power. Or to quote a 1964 Wizard of Id comic strip – “Whoever has the gold makes the rules.”
One of the open secrets of federal health agencies is the indirect manner agencies accept funds and indirect support from industry for research and programmatic purposes. In the 1990s, Congress established both the NIH Foundation and the CDC Foundation as pathways for industry and organizations to donate to agency activities and to partner with them. They were intended to facilitate public-private partnerships and be a protection against industry influence research outcomes. The foundations appear not to have complied with transparency regulations so much so thatCrossFit, Inc. has filed a Freedom of Information Act (FOIA) lawsuit to force compliance. Crossfit has concerns about the influence of the soda industry on dietary recommendations. Their initial attempt to gather information provedunsuccessful.
The CDC Foundation raised over $43million in Fiscal Year 2016-2017. It providesa list of its donors; however, it does presently post specific informationabout the level of each donation. Thecorporate donors are vast including Bayer, Bill and Melinda Gates Foundation, BloombergPhilanthropies, Coca-Cola Company, Cargill, GAVI, Genzyme, the Guttmacher Institute,Janssen, Merck, Pepsico, Pfizer, Sabin Vaccine Institute, Vaccines andMedication in Pregnancy Surveillance System, many universities, including statesponsored schools (the question of taxpayer funded school donated to a federal agencythrough a foundation is a topic for another day), UNICEF, the state ofCalifornia, and Major League Baseball.
Examples of how this works:
- The Contraceptive Use Module For States Project being conducted by the CDC. The CDC Foundation has ‘partnered with the Guttmacher Institute for a $2.8 million project to “support state use of a module on the Behavioral Risk Factor Surveillance System that assesses contraceptive use among women aged 50 and younger. This effort will allow for the development of state-level estimates of the methods of contraception used and reasons for not using contraception.” From their website, one learns that the Guttmacher Institute was founded in 1968 as the Center for Family PlanningProgram Development. The Center was originally housed within the corporate structure of the Planned Parenthood Federation of America (PPFA). Its early development was nurtured by Alan F. Guttmacher, an obstetrician-gynecologist, author and leader in reproductive rights who was PPFA’s president for more than a decade until his death in 1974. TheCenter was renamed in Dr. Guttmacher’s memory, and the Guttmacher Institute incorporated as an entirely independent nonprofit policy research institute with its own Board in 1977 but remained a special affiliate of PPFA through2007. Among the activities of the Guttmacher Institute focus are contraception and abortion. The Guttmacher Institute is a leader in promoting access to abortion services. As an aside to this matter, the most recent past Director of the Eunice Shriver National Institute of ChildHealth and Human Development (NICHHD) at the NIH was Dr. Alan Guttmacher, nephew of Alan F. Guttmacher. During the early days of his tenure at the NICHHD he continued to serve on the Board at the Guttmacher Institute and NICHHD before, during and after his tenure have provided grant funds to the Guttmacher Institute.
- The Bill and Melinda Gates Foundation has poured millions into the CDC Foundation for numerous projects including the development of surveillance systems, paying for scientists from financially disadvantaged countries to attend conferences, and projects related to rotovirus, norovirus, tobacco control, and zika. In one instance, they funneled the funding through Bloomberg Philanthropies, who have also provided at least $10 million to the CDC Foundation for various projects including tobacco use surveillance.
The Foundation for the NIH (FNIH) has raised over $1 billion in its 22-year history. Its website states that, “FNIH develops collaborations with top experts from government, industry, academia and the not-for-profit sector and provides a neutral environment where we can work productively toward a common goal.” In itsMay 2018 report, the Board of Directors include former NIMH director Thomas Insel (now in the corporate world); and many pharmaceutical industry individuals such as the Chief Medical Officers of both Pfizer and GlaxoSmithKline, This report also states they have raised over $400million for various NIH Institutes and Centers and a total of more than $555million. Three of the accomplishments include:
- The NIH, the FNIH and twelve leading pharmaceutical companies launched the Partnership for Accelerating Cancer Therapies (PACT), a five-year, ~$220million public-private research collaboration as part of the Cancer Moonshot.PACT will identify and develop robust, standardized biological markers of disease to advance new immunotherapy treatments that harness the immune system to attack cancer.
- The FNIH, in collaboration with the National Institute of Allergy and Infectious Diseases (NIAID), has launched a new project to shorten the treatment times of tuberculosis (TB) in drug–sensitive patients through individualized therapy. The $24 million project, “Using Biomarkers to Predict TB Treatment Duration”(PredictTB), is funded in part through a $13 million donation from the Bill& Melinda Gates Foundation, with management support provided by the NIAID and the Catalysis Foundation for Health.
- The NIH, the FNIH, five leading pharmaceutical companies, together with Verily(Alphabet Inc.’s research organization devoted to the study of life sciences)and the Michael J. Fox Foundation (MJFF), launched in February of 2018 the Accelerating Medicines Partnership for Parkinson’s Disease (AMP PD), a five-year, $24M million public-private research partnership to identify and validate diagnostic, prognostic, progression and predictive biomarkers for PD. Some of the goals of this partnership are to improve clinical trial design, better patient stratification, the ability to monitor disease progression, and the potential to identify new pathways for therapeutic development.
MACH Trial defunded: Sharyl Attkisson’s show, Full Measure ran a story this past week regarding the $100,000 NIH Research Study slated to test moderate alcohol consumption health effects. (9) Her report shared internal emails from NIH employees within the National Institute of Alcohol Abuse and Alcoholism (NIAAA) who were actively recruiting industry sponsorship, which violates NIH policies. While the NIH had committed to at least $10million, over $67 million had been committed to the project by Anheuser-Busch In Bev, Carlsberg Breweries A/S, Diageo plc, Heineken, and Pernod Ricard USA LLC. In the June 2018 announcement: “The National Institutes of Health plans to end funding to the Moderate Alcohol and Cardiovascular Health (MACH) trial…The decision is based on concerns about the study design that cast doubt on its ultimate credibility…significant process irregularities in the development of the funding opportunities for the MACH funding awards undermined the integrity of the research process…NIH Office ofManagement Assessment (OMA) determined that a small number of NIAAA employees violated NIH policies in soliciting gift funding and circumvented standard operating procedures designed to ensure a fair competition for NIH funding. These policy violations were committed by NIAAA employees prior to the involvement of the Foundation for the National Institutes of Health (FNIH). (10)
The FNIH website states: “Prospective epidemiological studies consistently relate moderate alcohol consumption with lower risk of cardiovascular disease, ischemic stroke, and type 2 diabetes. However, this association remains controversial due in part to the lack of gold-standard randomized evidence. This project is intended to meet the need for a clinical trial. The primary study objectives are: 1) determine the effects of one serving of alcohol daily, compared to no alcohol intake, on the time to incident cardiovascular disease among adults at above average cardiovascular risk; and 2) to determine the effects of one serving of alcohol daily on the time to incident diabetes among participants free of diabetes at baseline. The study design will be a randomized, multicenter, international,assessor-blinded, parallel group, balanced clinical trial. FNIH has been asked to secure private-sector funding and to create an arms-length relationship between funders and NIH, in order to ensure an unbiased trial.”
In a Washington Post article about the halting of the study (11), an exchange between Senator Patty Murray and NIH Director Francis Collins was included, “Sen. Patty Murray (D-Wash.) asked whether what happened at NIAAA with the alcohol study might have happened at other institutes in the sprawling NIH operation. Collins answered, “I’m very concerned this might be the tip of a larger iceberg,” adding that his investigators are looking for other examples at NIH.” The article also mentions that in April, Dr. Collins called an abrupt halt to the planned receipt of funding from dozens of pharmaceutical companies for the $400 million Opioid ResearchPartnership. In making the announcement, Dr. Collins stated, “I fully embrace [the] recommendation that NIH should vigorously address the national opioid crisis with government funds and decline cash contributions through partnerships from the private sector,” Collins said in a statement. Instead of accepting cash from drug companies interested in teaming up, Collins said the NIH would lean on industry only for help in setting up a clinical trial network, establishing common biomarkers for drug development, and sharing data.” (12) There is at least one organization calling for an Inspector General investigation.
In addition to
the two Congressional formed nonprofits there are also a number of “Friends of
the___” type collaborations and non-profits whose functions are to promote the
agenda of the agency they support and to funnel industry funding to the
agency’s projects. One example:
The Friends of NCBDDD is a coalition of government and private sector participants who work together to enhance the mission and activities of the National Center on Birth Defects andDevelopmental Disabilities (NCBDDD) (at the CDC). The member groups include numerous medical trade associations including the American Academy ofPediatrics and the American Psychological Association; non-profits such as the Tourette’s Association, Autism Speaks; state agencies; businesses; and even large law firms involved in government relations. This organization ‘shares information’ and works together to push policies and legislation.’ The organization provides no funding information, nor does it list the members of its “Executive Committee’. The industry has influence directly or indirectly through the funds it provides to the trade associations and non-profits involved.
Concern 3: Treating All Research Outcomes as Equal in Media Discussions: Not all research is equal. That is a fact. There is a reason the gold standard of research developed in the 20th century. That gold standard is the double-blind, placebo-controlled clinical trial. In truth, there is a research hierarchy that the public should be better informed. There is a discussion among the experts about the need for a topology focus – a research matrix per se – matching the research question to the type of research needed to be conducted to answer the question with credibility. One interesting article on the topic can be found at: https://www.cebma.org/wp-content/uploads/Petticrew-Evidence-hierarchies-and-typologies.pdf
There are times in which a randomized, double-blind, placebo-controlled clinical trial is neither feasible or practical. That is a discussion for a different day. It can be summarized by explaining that when the intervention is not a single agent like a drug or a vaccine but is a multi-mode intervention or an intervention requiring person to person interaction such as acupuncture, chiropractic or massage; blinding and placebo-controlled are not practical. I would also suggest that longterm studies that function outside of a controlled environment are ripe for non-compliance. (A major Vitamin E clinical trial is an example, where a significant portion of the participants were non-compliant.) I would also issue a caution about the misuse of the term ‘evidence-based’ by some who seek to suggest that the decision to use a different approach or product is not also based in scientific evidence. That too is a conversation for another day. Too often it is sophomoric “my science is better than your science’ bullying technique.
Two of the specific types of research that I have concerns are being given a higher level of prominence in the news than they warrant are surveys and epidemiology, especially epidemiological reviews of administrative(billing) records and electronic health records. One scholarly paper “A nurses’ guide to the hierarchy of research designs and evidence” available at: http://www.ajan.com.au/Vol33/Issue3/5Broomfield.pdf provides a basic analysis and a pretty good graphic. Surveys are considered low on the hierarchy because they along with case studies have the greatest change of bias. Surveys can be manipulated easily by determining where the study will be conducted. The outcomes of asking questions for instance about stroke, alcohol consumption, even mental health likely will vary widely depending on where surveys are conducted, sometimes even within the same city. The number of individuals included in the survey and the survey questions themselves matter. The way an individual asks the questions may actually affect the response. And to quote the famous television doctor, Dr. House, “People Lie.” It is a human inclination to want to answer a question the way one thinks it should be answered on some issues.
After 18 years of following the CDC’s use of epidemiology to prove the safety of various vaccines or vaccine ingredients, I continue to be amazed at the lack of a vigorous pushback from scientists at the NIH and the academic community. One cannot answer a question of toxicology with a retrospective review of medical billing records or any other type of epidemiology. And yet, this is exactly what the CDC has put forward and been sanctioned through their contract with the National Academy of Sciences. Remember when I stated above, “He who has the cash has the power”? The CDC was the keeper of the funds to pay the National Academy for their evaluation of vaccine issues related to neurodevelopmental disorders. The CDC gave its marching orders to focus only on the epidemiology and ignore the animal studies and ther more profound research. They had the cash and thus the power. The National Academy complied.
For those who are unfamiliar with the details, the Federal National Vaccine Injury Compensation Program used 5 CDC epidemiological studies as their basis for denying over 5,000 families’ compensation for their children’s devastating vaccine injury in the Autism Omnibus proceeding. How do I know this? Because I have seen the letter one of the families received from the courts explainingthe basis for the denial. These studies have problems in design and implementationand at least two of them were managed by a researcher who has been on the OIGMost Wanted list since 2012.
It is not just the CDC’s vaccine-related epidemiology research that concerns me. One group of studies paid for by the CDC and conducted by some of the same researchers involved in their autism-vaccine research looked at alcohol consumption during pregnancy. The methodology of the study, combing through the Danish health records and then interviewing the mothers about their alcohol consumption during pregnancy, sometimes years later, and then a review of the child’s medical records resulted in the publication of ‘research’ that set decades of public health messaging about alcohol avoidance on its ear. The BBC headline in 2012 read “Moderate drinking during pregnancy branded ‘safe’”. (15) This series of research continues to get media play, “Opinion: A couple of drinks when you’re pregnant really isn’t that bad “(16) The CDC is on the record on their website in stating there are no safe exposure levels to alcohol during pregnancy. Sadly, epidemiology can be manipulated. Think Enron and accounting. Based on years of reviewing how it’s been manipulated to achieve a predetermined outcome, I have very little confidence in this type of research. At the end of the day, why take a risk with your child’s neurodevelopment? Is any glass of wine so important as to potentially set your child up for a lifetime of challenges?
Some of the most egregious promotions of scientific outcomes related to studies with negative outcomes are those related to dietary supplements. The news loves to hate vitamins and often overplays the power of a study or how it compares to other research. An informative article available at http://www.thebody.com/content/75580/are-vitamin-pills-a-waste-not-so-fast-dissenting-e.html details the yo-yo media coverage and many of the problems in nutrient research.
A final area of research focus that I have concerns about are studies known as a meta-analysis or systematic review. The Cochrane Collaboration began promoting this method of analyzing all the studies in a certain topic and judging it. This is increasingly popular and being utilized by federal policymakers to look at a number of issues including the non-pharmacologic pain management research. There are a number of challenges with this emphasis on meta-analysis. The first is asking too broad a question. For instance, a recent meta-analysis commissioned by federal officials to look at non-pharmacologic pain management research claimed to have been a comprehensive analysis of all clinical trials related to all complementary and alternative therapies. The actual analysis focused on a handful of therapies and even within that analysis, there were shortcomings. The second is the apriori determination to only accept randomized, placebo-controlled trials. If the NIH has never funded these types of studies, and if none exist in the literature, how can the analysis provide an accurate assessment? These types of analysis fail to incorporate the full body of evidence or address the reality that there are times placebo-control is impossible. The other aspect, particularly in complementary therapies, is that if the researcher has a bias against, or a lack of extensive understanding of the field, the ability to accurately review the data isskewed.
Conclusion: At the end of the day, all of the issues detailed above boil down to one thing – integrity. Researchers who lack the integrity to disclose industry relationships and payments undermine the entire foundation of public trust in science. The CMS Doctors payment dataset is only accurate if doctors are honest about the payments they receive from industry. The Congressionally created foundations established to funnel industry funds to agencies must operate with full transparency in order to ensure true independence in research. Friends oforganizations need to also be transparent in their staff/leadership andfunding.
Abraham Lincoln once said, “Nearly all men can stand adversity, but if you want to test a man’s character, give him power.” The public has entrusted government officials and academic researchers with a great deal of power. It is my hope that as Dr. Collins begins investigating the ‘tip of the iceberg’, that we can have anhonest dialogue in the public forum regarding these matters and affect real change.
One recommendation I would put forward today is a change in HHS advisory committee policies. At least one- third of the members of each research and policy related advisory committee should be public members – individuals or parents whose lives are directly affected by the decisions of that body; individuals who are not part of the government-academic-industry communities, but rather advocates and individuals from the general public. This is a first step in ensuring sunlight on government research matters. A second recommendation is that Congress needs to do annual reviews of the CDC and NIH Foundation to ensure they comply with their transparency requirements. A third is that journals and the NIH need to settle on a consistent conflict and funding reporting style and include it in the information provided in the Abstract through the PubMed system. Someone within the PubMed management needs todo regular reviews to ensure compliance and even do evaluations to confirm that authors with numerous studies consistently report their conflicts and funding.
And in closing, I’ll quote Theodore Roosevelt, “No nation can be really great unless it is great in peace, in industry, integrity, honesty. Skilled intelligence in civic affairs and industrial enterprises alike; the special ability of the artist, the man of letters, the man of science, and the man of business; the rigid determination to wrong no man, and to stand for righteousness—all these are necessary in a great nation.”
I pray we all continue to strive towards being and remaining a great nation.
Always,
Beth
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