A won­der drug’s dark side

Toronto Star - - FRONT PAGE - DAVID BRUSER AND JESSE MCLEAN STAFF RE­PORTERS

Hun­dreds of thou­sands of teen girls in Canada have safely taken Gar­dasil, a vac­cine shown to pre­vent HPV. But a Star in­ves­ti­ga­tion has found that since 2008, at least 60 Cana­di­ans ex­pe­ri­enced de­bil­i­tat­ing ill­nesses af­ter in­oc­u­la­tion. Pa­tients and par­ents say the in­ci­dents point to the im­por­tance of full dis­clo­sure of risks

By the time Kait­lyn Arm­strong re­ceived her third and fi­nal in­jec­tion of the popular HPV vac­cine Gar­dasil, pain had spread through the Whitby teen’s body, mi­grat­ing from her back to her knees to her hips.

Af­ter her first dose, Natalie Ken­zie of Lon­don de­vel­oped egg-size lumps on the soles of her feet, her joints swelled and her limbs twitched un­con­trol­lably.

Be­fore get­ting the shots, both 13-year-old girls were told the vac­cine had no sig­nif­i­cant risks. And as they strug­gled to learn what ailed them, and be­gan to be­lieve Gar­dasil played a role, doc­tors dis­missed their con­cerns.

Hun­dreds of thou­sands of teenage girls in Canada have re­ceived the vac­cine’s three doses, the vast ma­jor­ity with­out in­ci­dent.

Reg­u­la­tors, in­clud­ing Health Canada and the FDA in the United States, cite com­pre­hen­sive clin­i­cal tri­als and other data that show the vac­cine’s well-stud­ied safety and ef­fi­cacy.

But since 2008 at least 60 girls and women in Canada have con­vulsed or de­vel­oped dis­abling joint and mus­cle pain and other de­bil­i­tat­ing con­di­tions af­ter re­ceiv­ing Gar­dasil.

One needed a wheel­chair, an­other a feed­ing tube. A 14-year-old Que­bec girl, Annabelle Morin, died two weeks af­ter re­ceiv­ing the sec­ond in­jec­tion of the vac­cine.

It was 7:30 p.m. on the night of Dec. 9, 2008, when her mother, Linda, found her in the tub, her head un­der­wa­ter and turned to the side.

The paramedics lifted Annabelle’s body on to a stretcher. “I put a blan­ket on her, say­ing, ‘She’s go­ing to freeze,’ ” Linda re­called. “I did not know she was al­ready dead.”

The Que­bec coro­ner’s of­fice said the cause of death was drown­ing, yet also said that any role Gar­dasil might have played should be fur­ther in­ves­ti­gated.

In the cases dis­cussed in this ar­ti­cle, it is the opin­ion of a pa­tient or doc­tor that a par­tic­u­lar drug has caused a side-ef­fect.

There is no con­clu­sive ev­i­dence show­ing the vac­cine caused a death or ill­ness.

Like Ken­zie and Arm­strong, many of the girls say the vac­cine was pushed on them by school of­fi­cials, nurses or doc­tors who un­der­stated the risks, some­times claim­ing zero sig­nif­i­cant side ef­fects de­spite the ex­is­tence of a list of rare but se­ri­ous vac­cine-re­lated re­ac­tions pub­lished by the drug’s maker.

The Star has found the girls’ con­cerns are not iso­lated, that in Canada im­por­tant safety in­for­ma­tion about the vac­cine has not been com­mu­ni­cated to many young pa­tients and their par­ents.

As part of its on­go­ing in­ves­ti­ga­tion into drug safety, the news­pa­per an­a­lyzed side­ef­fect re­ports from a Health Canada data- base, and in­ter­viewed reg­u­la­tors, a doc­tor closely in­volved in the vac­cine’s clin­i­cal trial and, in 12 cases, young women and par­ents who be­lieve the vac­cine caused con­sid­er­able suf­fer­ing.

Some of the girls have, af­ter sev­eral years, made par­tial re­cov­er­ies and are try­ing to live nor­mal lives. Oth­ers are still bounc­ing from doc­tor to doc­tor, look­ing for an­swers.

Ap­proved in more than 130 coun­tries, the vac­cine protects against strains of hu­man papil­lo­mavirus (HPV) that cause 70 per cent of cer­vi­cal can­cer cases and 90 per cent of gen­i­tal warts. Roughly 400 Canadian women die of cer­vi­cal can­cer each year.

HPV is a com­mon sex­u­ally trans­mit­ted in­fec­tion. By tar­get­ing girls in their young teens, health of­fi­cials seek to vac­ci­nate them be­fore they be­come sex­u­ally ac­tive. The vac­cine is in­ef­fec­tive for some­one al­ready in­fected with th­ese strains.

While Health Canada and the U.S. FDA say the vac­cine is safe, of­fi­cials in other coun­tries have sounded alarms. In 2013, Ja­pan’s health min­istry said it would stop pro­mot­ing the vac­cine while it looked into se­ri­ous side-ef­fect re­ports.

Gar­dasil was ap­proved in the U.S. in 2006, and Health Canada soon fol­lowed by is­su­ing Merck a li­cence to sell the vac­cine north of the bor­der.

Lead­ing health au­thor­i­ties have largely lauded Gar­dasil, a se­ries of shots that cost a to­tal of $400-$500 and that, in Canada, prov­inces pay for and public health nurses ad­min­is­ter in schools. The three shots are given over six months.

Merck-spon­sored tri­als found the vac­cine pre­vented nearly100 per cent of ab­nor­mal growths — pre­cur­sors to cer­vi­cal can­cer — re­lated to two HPV types. Tri­als also found se­ri­ous side-ef­fects were rare, with just five re­ac­tions among more than 11,000 Gar­dasil re­cip­i­ents that were found to be pos­si­bly, prob­a­bly or def­i­nitely re­lated to the in­jec­tion.

“I’m ex­tremely com­fort­able that this is a safe vac­cine,” said Dr. Jen­nifer Blake, pres­i­dent of the So­ci­ety of Ob­ste­tri­cians and Gy­nae­col­o­gists of Canada.

There was an in­tense lob­by­ing ef­fort be­hind Gar­dasil’s roll­out in 2007.

Eight months af­ter be­ing ap­proved for sale, a na­tional vac­ci­na­tion pro­gram was born. Ottawa com­mit­ted $300 mil­lion. In On­tario, of­fi­cials an­nounced that all Grade 8 girls would have free ac­cess to Gar­dasil.

Crit­ics were wary of the quick em­brace of Gar­dasil, say­ing the vac­cine’s long-term ef­fi­cacy and risk were un­known.

Kait­lyn Arm­strong said she and her fel­low eighth graders heard about Gar­dasil from a guid­ance coun­sel­lor dur­ing a short in­for­ma­tion ses­sion given at her Whitby school in Septem­ber or Oc­to­ber of 2009.

“She told us it was go­ing to pro­tect us from cer­vi­cal can­cer, it’s a re­ally good idea to get it. She was push­ing it. She didn’t talk about any com­pli­ca­tions or any of that stuff,” re­called Arm­strong, who is now 17 and wants to be a pe­di­atric nurse. “My grandpa had died a few months be­fore from can­cer, so of course I was right on board.”

At the time, Arm­strong danced 20 hours a week, played soc­cer and ran track. Af­ter the first Gar­dasil shot, the pain started in her back. Af­ter the sec­ond and third shot, it spread to other joints, her knees and hips. Amanda Dubreuil, who taught Kait­lyn at her Oshawa dance stu­dio, re­mem­bers what hap­pened next.

“It was one of the sad­dest things I’ve ever seen. When I first started teach­ing her, she was so in­cred­i­bly strong, one of the most phys­i­cally gifted girls I had seen in a while. Over the course of three months she started de­te­ri­o­rat­ing.”

Be­fore each of the three shots, a public health nurse asked Kait­lyn if she had any al­ler­gies. Each time, Kait­lyn said, she re­sponded, “Yes, I am al­ler­gic to metal,” and the nurses said noth­ing in re­sponse and then gave the shot. (Since Kait­lyn was a baby, metal, such as the snaps on an in­fant’s one­sie, would cause rashes on her skin, she and her mother said.) Kait­lyn says nei­ther the school nor the nurses told her that one of the in­gre­di­ents of the vac­cine is alu­minum salts.

There were nu­mer­ous vis­its to doc­tors, she had MRIs and other tests, and was given painkillers. Even­tu­ally a doc­tor di­ag­nosed her with fi­bromyal­gia, a pain dis­or­der.

Cit­ing pa­tient pri­vacy, a Durham Re­gion public health of­fi­cial said she could not dis­cuss spe­cific cases, but said Durham’s vac­ci­na­tion pro­gram ed­u­cates stu­dents about the benefits and risks, in­clud­ing al­ler­gies.

Merck, the com­pany that makes Gar­dasil, did not com­ment on Arm­strong’s case but said “if a pa­tient has a hy­per­sen­si­tiv­ity to any in­gre­di­ent . . . then Gar­dasil would be con­traindi­cated for that pa­tient.”

A re­cent anal­y­sis by sev­eral Canadian health-care ex­perts found “ma­jor dis­crep­an­cies” prov­ince to prov­ince in the qual­ity and com­plete­ness of vac­cine risk in­for­ma­tion given to stu­dents and fam­i­lies.

The 2011 study said such in­for­ma­tion gaps can have “a sig­nif­i­cant ef­fect on the legal va­lid­ity” of con­sent.

“It’s con­cern­ing be­cause it’s send­ing mixed mes­sages,” said one of the study’s au­thors, Dal­housie nurs­ing pro­fes­sor Au­drey Steen­beek. An ad­vo­cate of HPV vac­ci­na­tions, she said bet­ter in­for­ma­tion will help curb dis­trust of vac­cines.

The Public Health Agency of Canada says vac­cines have saved more lives over the past 50 years than any other health mea­sure, and have con­trolled se­ri­ous dis­eases such as po­lio and measles.

Gar­dasil’s prod­uct mono­graph — a tech­ni­cal, 61-page doc­u­ment — de­votes mul­ti­ple pages to a range of com­mon and rare side-ef­fects, some se­ri­ous, con­nected to Gar­dasil.

The par­ents of the young women in this story said the doc­u­ments they re­ceived were sparse and omit­ted some of the side-ef­fects in­cluded in the of­fi­cial doc­u­ment.

In Canada, when doc­tors, nurses, phar­ma­cists or pa­tients sus­pect a phar­ma­ceu­ti­cal or vac­cine has caused a side-ef­fect, they can file a re­port with Health Canada. The Star an­a­lyzed the reg­u­la­tor’s data­base of re­ports and found more than 50 “se­ri­ous” in­ci­dents, in­clud­ing at least 15 hos­pi­tal­iza­tions con­nected to the vac­cine since 2007.

In the U.S., where there is a public data­base of vac­cine-re­lated side-ef­fect re­ports col­lected from around the world, the Star found thou­sands of sus­pected cases, in­clud­ing more than 100 deaths.

While the num­ber and de­tails of th­ese re­ports may be con­cern­ing, it is im­por­tant to note that since Gar­dasil was ap­proved in June 2006, more than 169 mil­lion doses have been dis­trib­uted glob­ally, ac­cord­ing to Merck.

Sus­pected side-ef­fects listed in the Canadian re­ports in­clude: Con­vul­sions; more than 10 cases of joint, ab­dom­i­nal and other se­ri­ous pain; two cases of ana­phy­laxis, a se­vere al­ler­gic re­ac­tion; two deaths, in­clud­ing that of a10-year-old girl; and a hem­or­rhage, stroke and life-threat­en­ing heart con­di­tion. In many of the cases, the pa­tients were teenagers, of­ten 13 or 14 years old.

A Health Canada spokes­woman said, “None of the ad­verse events re­viewed have sug­gested any con­cern­ing trends or pat­terns linked to the HPV vac­cines in Canada.”

The spokes­woman also said that the avail­able data shows Gar­dasil to be “among the most ef­fi­ca­cious vac­cines.”

One of the side-ef­fect re­ports in Health Canada’s data­base re­lates to 14-year-old Frédérick St-Ger­main’s heart attack.

St-Ger­main was hunt­ing snow geese with her fa­ther and brother when she col­lapsed. It was Oc­to­ber 9, 2010. She had re­ceived her first Gar­dasil vac­cine nine days ear­lier.

St-Ger­main’s heart was stopped for 15 min­utes be­fore paramedics reached her ru­ral Que­bec home and re­sus­ci­tated her, said her mother, Mylène Boisvert. She spent 34 days in hos­pi­tal, six of them in an in­duced coma.

“I had to re­learn ev­ery­thing, things that a 2-year-old would have to learn,” StGer­main, now 18, told the Star.

Months later, af­ter a bat­tery of tests came up neg­a­tive, a car­di­ol­o­gist re­ported to Health Canada and Merck that he sus­pected Gar­dasil caused the girl’s heart attack.

Many of the girls in­ter­viewed by the Star said that as they strug­gled to learn what was ail­ing them, doc­tors told them the ill­nesses were imag­ined, that they had eat­ing or anx­i­ety dis­or­ders, that the prob­lems were in their head.

When Natalie Ken­zie of Lon­don also de­vel­oped di­ges­tive prob­lems, “the doc­tors tried to con­vince me I had an eat­ing dis­or­der,” said Ken­zie, now 17 and in Grade 12. A doc­tor made her cry, she said, when he told Natalie she was try­ing to harm her­self.

“It’s very sad be­cause what I see is the physi­cians are not ac­cept­ing the fact that th­ese young women have pain and is­sues,” said Dr. Diane Harper, who was the prin­ci­pal in­ves­ti­ga­tor of a ma­jor clin­i­cal trial for Merck as the com­pany was de­vel­op­ing the block­buster vac­cine for the world­wide mar­ket. “The docs in the trenches have been con­di­tioned to re­spond, ‘vac­cines don’t have side-ef­fects.’ ”

Harper, now the chair of fam­ily and geri­atric medicine at the Uni­ver­sity of Louisville in Ken­tucky, said Gar­dasil’s ap­proval by the FDA was fast-tracked un­nec­es­sar­ily, since the pro­gres­sion of an HPV in­fec­tion to can­cer of­ten takes decades and can be de­tected through regular pap screens. She said the vac­cine could have been an­a­lyzed over a much longer time frame.

“There could be harm,” Harper said. “You just don’t know un­til you look at it in the full pop­u­la­tion.”

Merck said it mon­i­tors re­ported ad­verse re­ac­tions and, “while no vac­cine . . . is com­pletely with­out risk,” health reg­u­la­tors around the world con­tinue to rec­om­mend its use.

But in pro­mot­ing the vac­cine, Harper said, health of­fi­cials of­ten omit the im­por­tance of still get­ting regular pap screens to pro­tect from the HPV strains not cov­ered by Gar­dasil.

The public is not only get­ting in­com­plete in­for­ma­tion about Gar­dasil from of­fi­cials in Canada; there are also con­flict­ing mes­sages from other reg­u­la­tors around the world, a mix of red flags and re­as­sur­ances that seem to only raise more ques­tions.

In Ja­pan, the health min­istry an­nounced in 2013 that it had re­ceived re­ports of in­di­vid­u­als who re­ceived the HPV vac­cine — the min­istry did not spec­ify whether it was Gar­dasil or an­other brand called Cer­varix — and “ex­pe­ri­enced sus­tained pain for which a causal re­la­tion to the vac­cine can­not be de­nied.” The min­istry also said that “regular vac­ci­na­tion should not be ac­tively en­cour­aged” un­til more was known about the side-ef­fects.

But a World Health Or­ga­ni­za­tion com­mit­tee said there was lit­tle rea­son to sus­pect the vac­cine as the cause con­sid­er­ing the ab­sence of sim­i­lar prob­lems in other coun­tries. It said each case in Ja­pan should be care­fully doc­u­mented and urged “a thor­ough search for a de­fin­i­tive di­ag­no­sis.”

And in the U.S., a re­view com­mit­tee rec­om­mended against Merck’s ap­pli­ca­tion to get Gar­dasil ap­proved for use among women aged 27 to 45 be­cause com­pany data did not show the vac­cine to be ef­fec­tive in this age range.

But Health Canada saw it dif­fer­ently, and in 2011 li­censed Gar­dasil for women up to age 45. “As the num­ber of women with pre-ex­ist­ing in­fec­tion in­creases with age, the over­all ben­e­fit is not as great,” the reg­u­la­tor said. “How­ever, there are pop­u­la­tions of older women who can still ben­e­fit from the vac­cine.”

Merck told the Star that the vac­cine is ap­proved for the older age range in more than 50 coun­tries.

Jen Keats, whose Guelph doc­tor as­sured her the vac­cine had no side-ef­fects, re­ceived the shot at age 29 and sub­se­quently ex­pe­ri­ences nau­sea, weak­ness and mi­graines. Keats’ doc­tor did not re­turn mes­sages left by the Star.

From her home in Laval, Que., Linda Morin, 55, re­called the night of her daugh­ter’s drown­ing, when she re­turned home from the hos­pi­tal and was ques­tioned by two po­lice of­fi­cers. She did not, at the time, have an ex­pla­na­tion.

Not un­til a few months later, when she read an ar­ti­cle about two young Span­ish girls who sus­pected Gar­dasil caused their hos­pi­tal­iza­tions, did Morin think she might have an an­swer.

She called her daugh­ter’s school, asked some ques­tions, took some notes and built a timeline.

Annabelle got her first Gar­dasil shot on Oct. 9, 2008. Morin re­mem­bered that on Oct. 25 Annabelle “came out of (her) room dis­ori­ented, she could hardly walk, she couldn’t speak. She was mum­bling.” Annabelle was also vom­it­ing and com­plained of a bad headache. Morin took her daugh­ter to the hos­pi­tal, where a brain scan turned up noth­ing. Soon Annabelle felt bet­ter.

The episode oc­curred 16 days af­ter her first Gar­dasil shot.

Annabelle got her sec­ond shot on Nov. 24. Af­ter about the same span of time, 15 days later, she died.

Morin says that de­spite the coro­ner’s call for an in­ves­ti­ga­tion into the role Gar­dasil played in her daugh­ter’s death, none oc­curred.

She sued Merck but aban­doned the legal ac­tion in part, she said, be­cause of dif­fi­culty find­ing a Que­bec doc­tor who would say Gar­dasil con­trib­uted to Annabelle’s death.

“I am not against the vac­cine,” Morin said. “I want peo­ple to be re­spon­si­ble about Gar­dasil. I am try­ing to in­form peo­ple.” Data anal­y­sis by An­drew Bai­ley

RANDY RIS­LING/TORONTO STAR

Kait­lyn Arm­strong says the nurses giv­ing her the HPV vac­cine Gar­dasil ig­nored her when she said she was al­ler­gic to metal.

RANDY RIS­LING/TORONTO STAR

Linda Morin found her 14-year-old daugh­ter Annabelle dead in the bath­tub in 2008, shortly af­ter she re­ceived her sec­ond in­jec­tion of the HPV vac­cine Gar­dasil.

At age 14, Frédérick St-Ger­main spent 34 days in hos­pi­tal — six of them in an in­duced coma — af­ter one shot.

Jen Keats, who got the shot at age 29, later ex­pe­ri­enced nau­sea, weak­ness and mi­graines.

Annabelle Morin, 14, died two weeks af­ter re­ceiv­ing sec­ond shot.

Natalie Ken­zie, then 13, had lumps on her feet, swollen joints.

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