From a mother:

A while ago I wrote this about particles in injections after vaccine stoppers are punctured:

June 12, 2011

Dear Dr. Markowitz:

I am writing to you as a concerned physician and a former researcher at the National Institute of Health (NIH). As we all know, Gardasil is a vaccine approved for prevention of cervical cancer caused by two specific HPV genotypes under the Fast Track Drug Development Programs. The Guidance for Industry, Fast Track Drug Development Programs-Designation, Development, and Application Review stipulates:

“Where an accelerated approval is based upon a surrogate endpoint or on an effect on a clinical endpoint other than survival or irreversible morbidity, postmarketing studies are ordinarily required “to verify and describe the drug’s clinical benefit and to resolve remaining uncertainty as to the relation of the surrogate endpoint upon which approval was based to clinical benefit, or the observed clinical benefit to ultimate outcome” (57 FR 58942, December 11, 1992).”

We wholeheartedly agree with your statement on HPV vaccines that, ”Post-licensure evaluation of vaccines plays an important role in monitoring the progress of immunization programs, demonstrating population impact of vaccines, and providing data for ongoing policy decisions.” [1] A vaccine without a science-based post-licensure monitoring system to evaluate its impact on the population should not be allowed to be marketed to the consumers.

The currently available HPV vaccines, Gardasil and Cervarix, are designed to prevent infection by two genotypes of HPV that may cause cell changes, which if persistent and not properly treated may lead to cervical cancer in 10-30 years. Therefore, we also agree with you that “ it will take decades before the impact of vaccine on cervical cancer is observed. More proximal measures of vaccine impact include outcomes such as prevalence of HPV vaccine types, incidence of cervical precancers and genital warts.” [1]

Monitoring the prevalence of HPV vaccine types is the most practical meaningful approach to analyze the impact of HPV vaccines, including Gardasil because cervical precancer CIN2 and CIN3 lesions are not irreversible morbidity even though these cellular changes were used as the surrogate endpoint in the clinical trials for evaluation of Gardasil as a vaccine for prevention of cervical cancer. Prevention of genital warts has never been the purpose for developing HPV vaccines.

However, we are disappointed to find no provision for implementation of an effective system to survey the prevalence of HPV vaccine types in your monitoring report [1]. The only relevant statement in the report – “Some states, such as Florida and Connecticut have made some HPV-related outcomes reportable…” seems to be just a token gesture concealing the lack of CDC efforts to formulate a meaningful post-licensure surveying system.

One suspects the reason the CDC has delayed a genuine monitoring system is that it does not want to introduce a reliable DNA-sequencing-based HPV genotyping method for post-licensure monitoring. HPV DNA sequencing may reveal many post-vaccinated women are actually developing cervical precancerous lesions and cervical cancer caused by vaccine-relevant HPV genotypes which may include HPV-16, HPV-18, HPV-31 and HPV-45. This would be a fact the vaccine manufacturer, the CDC, the FDA and the NCI would not want to face.

On record, the CDC [2], FDA [3], NCI [4] and the standard textbooks [5, 6] all recognize that DNA sequencing is the gold standard for HPV genotyping beyond a reasonable doubt.

As an informed physician, I have learned that the DNA sequencing technology is not too complex or too expensive for HPV genotyping in order to ensure safe and effective vaccination. In the very CDC report authored by you and your associates [1], a quoted reference states:

“… HIV genotype DNA sequence has been made reportable as part of a Centers for Disease Control and Prevention-funded multistate surveillance system to monitor trends in HIV drug resistance.”

This document confirms that the CDC has made HIV genotype DNA sequence in electronic file reportable to monitor trends in HIV drug resistance.

Cervical cancer initiated by persistent infection of certain genotypes of HPV is at least as life-threatening as infection by drug resistant HIV. For this very reason, the FDA approved the HPV vaccines under the fast track drug programs and allows the vaccines to continue to be marketed in spite of its potential serious harmful side effects to the consumers.

According to Section 112 Expediting Study and Approval of Fast Track Drugs of the Food and Drug Administration Modernization Act of 1997 cited in Appendix 1 of the Guidance for Industry, Fast Track Drug Development Programs-Designation, Development, and Application Review, under the provision EXPEDITED WITHDRAWAL OF APPROVAL, The Secretary (of HHS) may withdraw approval of a fast track product when a post-approval study of the fast track product fails to verify clinical benefit of the product.

Therefore, the CDC post-licensure surveys on the prevalence of HPV genotypes which cause cervical precancer or cancer among women who have already been immunized with the HPV vaccines plays a pivotal role in determining if the benefit of the vaccine outweighs its potential risk to medical consumers.

Based on available science and law, we hereby request that the CDC issue a directive to the vaccine manufacturers, vaccine distributors, state health departments and health care providers as follows:

“Any female patient who has been vaccinated with HPV vaccines who subsequently is diagnosed with Pap cytology results positive for cervical precancer or cancer, the electronic file diagnostic of the HPV genotype DNA sequence derived from the cervicovaginal cell suspension in the cytology sample is now reportable to the CDC.”

We believe this format of post-licensure surveys will not need any special funds from the government and require little effort to implement. The cost of continued post-vaccination cervical cancer screening is already part of the routine health care expense for all women. In this manner, the CDC will have the data for analyses to determine if Gardasil has indeed reduced the percentage of cervical precancers and cancers caused by the vaccine-targeted HPV genotypes.

Gardasil is known to be associated with high frequencies of anaphylactic reactions. It is estimated the rate of anaphylaxis reaction after Gardasil vaccination is 5 to 20 times higher than those identified in comparable school-based vaccination programs [7]. Gardasil may also play a role in triggering orthostatic hypotension [8]. Anaphylactic reactions or orthostatic hypotension may be the cause of syncope (fainting) commonly reported after Gardasil injections, and may lead to serious permanent disabilities or deaths as listed on the CDC record.

Therefore, we urge the CDC to institute a reliable science-based post-licensure monitoring system nationwide immediately to determine if the benefits of mass vaccination of young women against HPV infection for cervical cancer prevention in fact outweigh the risks of the vaccine.

Recently, the fast-track cancer drug Mylotarg was withdrawn after post-marketing studies raised new safety concerns and failed to confirm its effectiveness. Medical consumers need post-licensure survey data on Gardasil to be reassured that they are not receiving the risk of HPV vaccination for no confirmed benefits. Any drug approved via Fast-Track procedures using surrogate endpoints must be adequately and accurately monitored post-licensure – or not be marketed.

We are looking forward to receiving your response to this request.

Sincerely,

cc.

References

[1] Markowitz LE, Hariri S, Unger ER, Saraiya M, Datta SD, Dunne EF. Post-licensure monitoring of HPV vaccine in the United States. Vaccine. 2010; 28:4731-7.

[2] Vernon SD, Unger ER, Williams D. Comparison of human papillomavirus detection and typing by cycle sequencing, line blotting, and hybrid capture. J Clin Microbiol 2000; 38:651-5.

[3] http://www.fda.gov/downloads/MedicalDevices/DeviceRegulationandGuidance/GuidanceDocuments/UCM181511.pdf

[4] https://www.fbo.gov/index?s=opportunity&mode=form&id=da396b97ad6eb7ec4f7d511f85d9e325&tab=core&_cview=0

[5] Reference Book

[6] Reference Book Excerpt

[7] Brotherton JM, Gold MS, Kemp AS, McIntyre PB, Burgess MA, Campbell-Lloyd S; New South Wales Health HPV Adverse Events Panel. Anaphylaxis following quadrivalent human papillomavirus vaccination. CMAJ. 2008;179:525-33.

[8] Mosnaim A, Abiola R, Wolf M, Perlmutter L. Etiology and risk factors for developing orthostatic hypotension. American Journal of Therapeutics. 2010; 17: 86-91.

The following letter was sent by Dr. William Reichel, Georgetown University School of Medicine:

June 12, 2011

Dear Senator Mikulski,

As a physician and past researcher at the National Institute of Health (NIH), I am writing to your office because of my personal concern over the trail of tragedies left in the wake of people making decisions to follow CDC guidelines regarding the FDA approved quadrivalent HPV (qHPV) vaccine, Gardasil. We were led to believe that Gardasil “can prevent most cases of cervical cancer….” and “it can also prevent vaginal and vulvar cancer…” [1] Millions of trusting people around the world submitted to the administration of the qHPV vaccine believing it to be “very safe” and effective [1]. However we now learned that in clinical trials, the efficacy of Gardasil to prevent cervical cancer was never validated under the FDA fast track drug program. Furthermore, post-licensure monitoring of Gardasil as required by law to determine if Gardasil indeed reduces the incidence of cervical cancer or precancer caused by relevant HPV genotypes has also not occurred.

I have attached a copy of a letter to Dr. Laura Markowitz at the CDC which documents the concerns in detail. Validation of the efficacy of Gardasil would require a reliable, science-based DNA sequencing test to properly analyze HPV genotypes. Although this reliable method of analysis is the gold standard, it has not been implemented. Consequently, there is no valid scientific evidence that Gardasil can prevent cervical, vaginal or vulvar cancer.

Gardasil is known to be associated with a high incidence of potentially serious side effects which are also documented in the letter. It is imperative that the CDC institute a reliable post-licensure monitoring system nationwide immediately to determine if the benefits of mass vaccination of young women against HPV infection for cervical cancer prevention do in fact outweigh the risks of vaccination. We request that your office follows up to ensure that the CDC acts immediately to comply with the law in the interests of public health and safety. There is also no cost benefit to paying for a vaccine that is not effective. If there is no reliable method of monitoring HPV vaccinations for disease impact, there should be no marketing of HPV vaccines.

Thank you very much for your prompt attention to this issue and I look forward to hearing from you.

Sincerely,

[1] CDC. Vaccine Information Sheet: HPV Vaccine- Gardasil. May 3, 2011.

http://cdc.gov/vaccines/pub/vis/downloads/vis-hpv-gardasil.pdf. Accessed May 23, 2011.

Laura Keegan from New York State: I am licensed in the state of New York as a registered professional nurse (RN) and a family nurse practitioner (FNP).

Links to letters I wrote to Markowitz and Schiffmann and rep letter (as written to Senator Gillibrand) can be found in the beginning of my blog post.

I sent identical letters to my 2 state senators Kirsten E. Gillibrand and Charles E. Schumer and my Congresswoman Nan Hayworth, MD.

Norma Erickson, President of SaneVax Inc. As a private citizen, I sent letters expressing my concerns in regard to HPV vaccines to all of the Senators and Congressmen from my state of residence. The following letter is one I received in response to my concerns:

June 9, 2011

Dear Norma:

Thank you for contacting my office. It’s good to hear from you.

During the 112th Congress, the U.S. House of Representatives will address many critical issues that affect the state of Montana and the nation. When addressing these issues, the best information I receive comes directly from folks in Montana.

As Montana’s sole voice in the U.S. House of Representatives and member of the influential Appropriation’s Committee, I will continue working to ensure that Montana has a seat at the table when our country’s spending priorities are determined. It’s imperative that Congress focus on smart spending and balancing the budget by eliminating the waste, fraud and abuse that occur all too often in Washington, D.C.

I’m working hard to improve access to affordable healthcare, fighting to keep Montana small businesses out of the regulatory crosshairs, and advocating a plan to develop Montana-made energy. As a member of the Energy and Water Appropriations Subcommittee, I have and will continue to advocate a comprehensive energy approach that promotes the use of fossil fuels, alternative sources, conservation, and new technology development.

Thanks again for contacting me. If you get a chance, I encourage you to visit my website at http://www.house.gov/rehberg where you can find the latest news about what’s happening in Congress. Also, if you haven’t already done so, please be sure to sign up for my E-Newsletter at http://www.house.gov/rehberg/newsletter/ which will help keep you up-to-date with what is going on in Washington, DC and how it affects Montana.

Sincerely,
Denny Rehberg
Montana’s Congressman

Norma Erickson, President of SaneVax Inc. As a private citizen, I sent letters expressing my concerns in regard to HPV vaccines to all of the Senators and Congressmen from my state of residence. The following letter is one I received in response to my concerns:

June 15, 2011

Dear Norma:

Thank you for contacting me about the vaccine Gardasil. I appreciate hearing from you on this matter.

I recognize your concerns over the safety of Gardasil. You bring up many valuable points in your letter, and it demonstrates a deep level of commitment to this issue. I am taking your comments into careful consideration. As one of my constituents, your input is important to me. I’m listening to what you’re saying, and you can rest assured I will keep your thoughts firmly in mind.

Thanks again for getting in touch. Please contact me with any additional comments or concerns. Also, please visit my website at http://baucus.senate.gov for more information on current issues and to find out what I’m doing both here in Washington and at home to help Montana.

Sincerely,
Max Baucus

MB/jg

Norma Erickson, President of SaneVax Inc. As a private citizen, I sent letters expressing my concerns in regard to HPV vaccines to all of the Senators and Congressmen from my state of residence. The following letter is one I received in response to my concerns:

June 29, 2011

Dear Norma,

Thank you for contacting me with your concerns about the Gardasil vaccine. I appreciate the information you provided on this issue.

While vaccinations have saved countless lives by reducing the risk of very serious illnesses, I understand your concerns. I believe it is very important to evaluate all drugs and vaccines closely to make sure they are as harmless as possible — particularly among higher risk people like pregnant women, seniors, and children.

As this issue comes before the Senate, I will keep your views in mind. Please do not hesitate to contact me again if I can be of further assistance.

Sincerely,

Jon Tester
United States Senator

09.14.09 Letter to Dr Margaret Hamburg, MD Commissioner Food and Drug Administration