John Russell

john.russell@indystar.com

Harry, Sesame, Ramsey, Kolbe, Rocky and Peaches have something in common — all of these beloved pets were prescribed a new chewable flea and heartworm medicine. And now they're all dead.

Their owners wonder if the drug, known as Trifexis, was the cause.

Several things about the drug make them suspicious. Trifexis, like many new pet drugs, was not developed specifically as an internal medicine for dogs. One of its two active ingredients started out as a crop pesticide.

Trifexis, which was developed by Eli Lilly and Co.'s animal drug division, Elanco, based in Greenfield, has many reported side effects. An Indianapolis Star investigation found that one of its two active ingredients, spinosad, ranks third among all pet drug ingredients for reports of convulsions, fourth for blindness, sixth for aggression and paralysis, and seventh for reports of unconsciousness, according to the latest data available from the U.S. Food and Drug Administration.

The other active ingredient, milbemycin oxime, ranks fifth for convulsions and ninth for deaths.

Dog owners across the country have reported more than 700 deaths to the FDA since the drug hit the market in 2011. And the FDA estimates that for every side effect that's reported nine times as many go unreported.

Trifexis is far from the only pet drug with hundreds of side effects and deaths reported. The database includes more than 19,000 dog and cat deaths reported in connection with a wide variety of pet medicines.

But did Trifexis kill Peaches? Ramsey? Rocky? What is the risk of it — or of other pet medicines — killing your dog or cat?

To such questions, pet owners simply can't get an independent answer. Not from veterinarians. Not from the FDA, whose job it is to ensure drug safety.

The companies insist their drugs are safe.

In a prepared statement, Elanco told The Indianapolis Star: "It's critically important to understand that reports are not an indication of cause. For any given (Adverse Drug Event) report, there is no certainty that the reported drug caused the adverse event."

The company said it completed a "thorough review and analysis" earlier this year of all reports it received from pet owners and found "no established link between Trifexis use and death."

It said such complaints are so infrequent that it has received less than one reported death for every 10,000 doses it sold, which is considered "very rare," according to standards published by the Council of International Organizations of Medical Sciences.

Yet, in the first examination by a major news organization of one of the fastest-growing segments of the pharmaceutical industry, The Star found an industry far different from the human drug market, one with higher risk of unforeseen side effects, a legal arena that offers little protection to pet owners and marketing tactics that have been eliminated from the human drug market.

The Star examined public records, studies and drug reaction data, and conducted interviews with company officials, pet owners, scientists, lawyers, epidemiologists, regulators and veterinarians. They told the story of an industry that is looking for ways to shore up declining revenues from human drugs, repurposing molecules that had an array of original uses for people and crops, and pushing government officials to speed up the approval process.

Drug and medical-device companies are pouring millions of dollars a year into research and development of pet medicines, hoping they can help make up the difference for a slowdown in human drug approvals. There are specialized animal drugs for everything from arthritis and heart disease to obesity and kidney disease.

Retail sales of pet medicines in 2013 were $7.6 billion, up more than 60 percent from 2006, according to the Federal Trade Commission and Packaged Facts, a national market researcher. And the growth shows no sign of stalling, with sales projected to reach $10.2 billion by 2018.

Last year, the third-biggest initial public offering on Wall Street was a pet medicine company, Zoetis, a spinoff from drug giant Pfizer. This year, Lilly said it would pay $5 billion to acquire Novartis' animal medicine, which would make Lilly the animal health industry's second-largest player.

Yet the pace of change is raising safety concerns among thousands of pet owners, consumer groups and some veterinarians across the country.

The drug-development process for pet medicines is far shorter than for human drugs, which cuts costs but increases the health risks to the animals, several epidemiologists and statisticians told The Star.Once these drugs are released on the market, there are few checks on company claims of product safety.

Some drugs aren't even approved for animal use but are commonly prescribed to animals. Their safety record isn't even tracked by the government, meaning it's impossible for consumers to make informed decisions.

And when animals die, the companies don't have to shell out big legal settlements. Pet owners usually can recover only the replacement cost of the animal — often no more than $100.

While drug companies have paid billions of dollars to settle complaints about human drugs, they sometimes resolve consumer complaints about pet medicines with polite letters and payments not even large enough to cover the cost of veterinary treatment.

Dozens of human drugs have been removed from the market because of safety concerns, but The Star was unable to find a single pet drug that was permanently pulled for similar reasons. The message is clear: A dog is just a dog, and a cat is just a cat.

In 35 states, including Indiana, courts have rejected damages based on the emotional relationship between an owner and a pet.

And industry lawyers are fighting to keep it that way. "If tens of thousands of dollars are at stake every time a pet is injured or killed, pet litigation will become a cottage industry," wrote attorneys representing the American Veterinary Medical Association, the Animal Health Institute and other powerful associations in 2012.

Still, the industry's marketing departments are sending a different message: "Your pet is a member of the family." Why? Studies show pet owners who share that view spend more than twice as much on veterinary care.

All this creates a marketplace where independent information is scarce and drug company money plays a role in outside research, continuing education and regulatory review. In stark contrast to the world of human medicine, veterinarians, researchers and industry are free to work closely together, with little to no transparency about drug company freebies and speaking fees paid to veterinarians.

Such undisclosed payments have been all but banned from the human drug market, where too much is at stake to risk even the appearance of bias in medical decisions.

But with pet medicines, it's a different story.

Dr. Nimu Surtani peered at the clock. It was 4 a.m., and his phone was ringing.

A friend, who was staying in his house in Noblesville, was on the line. She was watching Surtani's two dogs while he was on winter vacation in Texas with his wife, Laura, and two sons.

Something was wrong with Sesame, Surtani's 65-pound golden doodle, the friend said. The dog had awakened her to go out, then collapsed on the patio. He couldn't stand up.

The day before, Sesame had vomited twice and was wobbly, the friend said. Now she was rushing the dog to an emergency vet clinic nearby.

It was Dec. 31, 2013, normally a festive holiday. Not today.

When Surtani reached the vet on the phone, she told him Sesame was alert and seemed to be stable, although his heart rate was a bit high and his blood sugar was a little low. She didn't see anything that would explain his sudden inability to walk, such as signs of a heart attack, a rupture or bleeding, Surtani recalled.

Surtani, who earned a medical degree from the University of Texas in 1991, couldn't stop himself from trying to diagnose the situation.

"To me, it seemed like a big problem," Surtani recalled. "This is a healthy dog, and he's gone down quick."

Sesame's early lab results showed his kidney function was fine. Blood count was normal. One of the liver functions was slightly elevated.

Surtani, a surgeon, wondered if his dog might have a serious gastrointestinal problem that would require an emergency operation. Sometimes big dogs will eat something strange — a sock or a hat — and get their intestines twisted. He asked the vet to prepare the dog for surgery, just in case. She warned him it would cost $3,000. Surtani, who described himself as "pretty frantic," said go ahead.

He hung up, wondering about other possible causes. "I didn't know if he had a herniated disk in his back or something that would knock his legs out," he said.

Fifteen minutes later, his phone rang.

"We put him on the X-ray table, and he crashed and died," Surtani recalled the vet saying. "I couldn't save him."

Surtani was stunned, speechless. It made no sense.

"You could not kill a dog quicker"

Both of Surtani's golden doodles, Sesame and Cricket, had been completely healthy. The Surtanis had gotten them eight years earlier as pups. They had undergone no surgeries, aside from being neutered seven years earlier. The family walked the dogs every day, usually four or five miles. They loved to run, leap and play with Surtani's boys, Nels and Tate. Sesame was affectionate, never bit anyone, was the "star of the class" in obedience school, Surtani said, a "very regal dog."

Just a month before he died, Sesame had had his teeth cleaned, a procedure that included putting him under a general anesthetic so he wouldn't nip the veterinarian. He had come out of it fine. According to medical records Surtani provided The Indianapolis Star, Sesame had a clean bill of health on Nov. 12, with every system rated normal.

Now Surtani racked his brain for answers.

On the phone with the emergency veterinarian, Surtani learned that Sesame hadn't responded to CPR, nor to epinephrine, an emergency drug used to treat patients after a heart attack.

The veterinarian had taken X-rays in search of more clues. She didn't see anything wrong with the heart. The lungs were perfect. There was nothing abnormal in the belly.

In short, the veterinarian didn't have an answer. She apologized and asked Surtani to wait for the animal surgeon, who would be arriving shortly.

An hour or so later, the surgeon called. After a brief chat, he asked for permission to conduct an autopsy, an unusual and costly step in a dog's death. Surtani consented. He wanted an answer.

"You could not kill a dog quicker," Surtani recalled, "unless you gave him the wrong medicine and put him to sleep."

When the veterinary surgeon called Surtani back, he said he had cut open Sesame's abdomen. There was nothing unusual aside from an adrenal gland that was a little larger and firmer than usual.

Maybe Sesame had some sort of adrenal tumor, the surgeon said, that may have shot out adrenaline and killed the dog, a condition called pheochromocytoma.

Surtani didn't know about that. The dog's heart hadn't been racing. His exertion was normal. There was no evidence he had pheochromocytoma.

"At that point, I just thought, OK, there's no answer."

'She was star-gazing, stumbling around'

Across the country, pet owners were having similar experiences, and suspicions were rising about a new flea and heartworm medicine — Trifexis, which was developed by Lilly's animal drug unit, Elanco, and is now a top-selling pet medicine.

Eamonn Kneeshaw of Clearwater, Fla., said his veterinarian recommended Trifexis for his 12-year-old dog, a mixed-breed cocker spaniel and poodle named Harry. After his first dose in May 2013, Harry vomited and refused his favorite foods. His back legs went out. A month later, after several hospital visits and $6,500 worth of medical bills, Harry was dead.

Rebecca Haaland of Scott, La., gave her 1-year-old Scottish terrier, Ramsey, his first dose of Trifexis in April 2013. Six months later, he was dead. The vet said the dog must have gotten into something. The enzymes in his liver were extremely high.

Lou Gallo of Radford, Va., gave his dog, a 6-year-old Jack Russell terrier mix named Peaches, her first dose of Trifexis in June 2012. A month later, Peaches was dead.

Although there is no proven link between the deaths and Trifexis, some bereaved pet owners, fearing the drug had killed their dogs, mobilized to get the word out.

Kneeshaw drives a Hummer with huge letters in the back window: "Warning: Trifexis killed my dog and is killing many more every day."

Gallo started a Facebook page now called "Does Trifexis Kill Dogs?" as a memorial to his dog, and it has attracted visitors from all over the country. Scores of people have posted similar stories on the page. By last month, the site had more than 6,000 "likes." Tens of thousands of people had visited the page.

A few television stations around the country ran stories featuring local pet owners.

Gallo's Facebook page lists a handful of animal clinics, from New York to California, that refuse to carry Trifexis.

Dr. Corinna Tressler, veterinarian and owner of the Green Country Veterinary Hospital in Glenpool, Okla., refuses to give it to her patients. One of her technicians got a free sample and gave it to her dog, and it had seizures, Tressler said.

But many other vets say they swear by the medicine, and sales remain brisk. Dr. David Morgan, a veterinarian and founder of Academy Animal Hospital in Greenwood, says he has administered more than 15,000 doses and has not seen any serious reaction. He suspects that many of the adverse events are completely unconnected to the drug.

"If you had a glass of water at my office, drank it and walked into the parking lot and had a heart attack, did the water cause it?" he said. "Or were you going to have a heart attack anyway?"

Amid heightened public concern, the American Veterinary Medical Association eventually issued a report saying there was no definitive link between Trifexis and dog deaths.

It started as a crop pesticide

The Trifexis story began in 1982 when a Lilly scientist was on vacation in the Caribbean islands. He noticed a lot of flies in the area — except around a nonoperating rum still.

He took a soil sample near the still, analyzed it and discovered it contained a bacterium produced by fermentation. Scientists discovered that spinosad attacks the nervous system of insects, causing rapid death.

The company developed spinosad for agricultural uses, along with a partner, Dow Chemical. The U.S. Department of Agriculture eventually approved it for use on more than 100 crops, including apples, almonds, tomatoes and eggplants.

Elanco got approval to use spinosad, under the brand name Comfortis, as a flea preventive for dogs in 2007 and for cats five years later.

In 2011, Elanco won approval to combine spinsosad with another compound called milbemycin oxime, which was used in heartworm medicines. The new medicine was called Trifexis.

The beef-flavored tablet is designed to prevent or kill a raft of dangerous parasites found around plenty of yards and homes, including hookworm, heartworm, roundworm and fleas.

It "starts killing fleas in 30 minutes," an Elanco brochure says.

As reports of side effects came in, Elanco updated the product label in 2012 at the request of the U.S. Food and Drug Administration to include adverse events of vomiting, depression, lethargy, itchy skin, anorexia, diarrhea, trembling, shaking, ataxia (appearing wobbly), seizures, hypersalivation and skin reddening.

'Rigorously tested and approved as safe'

Earlier this year, Laura Surtani was surfing the Internet and came across one of the message threads critical of Trifexis.

Sesame had been on Trifexis for nearly a year. The Surtanis' veterinarian had switched both Sesame and Cricket from Sentinel, another anti-parasitic medicine.

Because they were leaving on vacation, the family had given both dogs a dose of Trifexis a week early. The monthly tablet should have been safe; according to Lilly's clinical trials, the medicine had tested safe in dogs even when it was given at five times the highest recommended dose for six straight months.

Nimu Surtani started browsing the Web as well. The complaints sounded familiar. One owner after another posted the same basic story: My dog became lethargic, lost its balance and didn't seem to have the ability to right itself or stand up. Its hind legs failed.

Surtani could relate. And he began to suspect Trifexis. "I had a healthy dog that was on one medicine ... who within five or six days of taking this pill collapsed and died, with no other medical proof that it was anything else," Surtani said. "Essentially, with what I do, you put two and two together and it usually means four."

Although he had no proof, he felt he had ruled out all other possible causes. "I immediately knew, right or wrong, there was probably a correlation," he said.

The makers of Trifexis firmly disagree with Surtani's opinion. "There continues to be no established link between Trifexis use and death," Elanco said.

Elanco declined to let The Star see a copy of a review it conducted into the deaths reported in connection with Trifexis. Neither would it reveal the exact rate of death reports, saying it was planning to submit the findings to a peer-reviewed scientific journal and that it didn't want to compromise the findings. In the meantime, it is standing firmly by its product.

"Trifexis has been rigorously tested and approved as safe by the U.S. FDA, the European Medicines Agency and many other countries around the world," Elanco said.

'Experimenting... by putting it out on the market'

Like many pet owners, Surtani assumed that pet medicines approved by the FDA were as thoroughly tested as human drugs.

"You think if a big pharmaceutical company is putting out an expensive medicine," he said, "it's gone through the same rigorous testing they're putting human drugs through."

But The Star found that's not the case.

Trifexis was tested on 751 dogs in 15 trials, according to Elanco's drug application filed with the FDA. That's a far smaller sample than used for typical human drugs.

Epidemiologists consulted by The Star said such a small sample increases the risk of unforeseen side effects.

The average pet medicine is tested on only 200 to 300 animals, according to the FDA, compared with 5,000 people for human drugs. Some human drugs are tested on far more subjects. Lilly's blood-thinner Effient, for example, was tested on more than 13,000 people.

That can make a big difference, allowing researchers to see how a drug works on a broad range of subjects, at different ages, under different conditions. So pet drugs, as a whole, are more likely to have unforeseen side effects.

"If you have something that happens in only one in every thousand creatures, and you test it on 300, chances are you can miss that," said Dr. Christine Petersen, a veterinarian and associate professor of epidemiology at the University of Iowa.

Peter A. Lachenbruch, a retired professor of public health at Oregon State University and former director of the FDA's Division of Biostatistics, said: "You would be very lucky to detect it in a small study. That would be an unacceptably high rate, certainly in humans and most likely in animals."

Surtani, who lost a beloved pet, put it in harsher terms. "Basically," he said, "they're experimenting on normal dogs by putting it out on the market."

No drug is completely safe. Even at a higher rate of testing, unsafe human drugs have slipped through. That's because some side effects are so rare they do not show up until the drug is used by millions of patients over long periods of time.

Such was the case with Vioxx, an anti-inflammatory drug used to treat arthritis. The FDA approved it in 1999 to treat osteoarthritis and acute pain. But Merck was forced to withdraw it from the market. Five years after approval, when more than 25 million people had taken the drug, it was linked to tens of thousands of serious heart attacks.

The FDA says it lacks the regulatory authority to mandate the recall of animal or human drugs. All it can do is issue a warning and work with manufacturers to launch a voluntary recall.

Drug companies also have pulled dozens of human drugs for safety reasons.

Health officials consulted by The Star said the smaller sample size for pet medicines, and the fact that such drugs are used across diverse species and breeds, makes it doubly important to collect safety data after a drug is on the market.

Despite the higher risks reported in connection with pet drugs, The Star was unable to find a single case since at least 2008 when a pet drug was pulled from the market for anything other than a temporary manufacturing issue, such as the contamination of a small batch.

'Money, I mean, that's the simple answer'

The Star asked several animal health professionals why that smaller sample size is used for pets. And most offered the same answer.

"Money," said Dr. Michael Conzemius, a veterinary surgeon and director of the University of Minnesota's Clinical Investigation Center. "I mean, that's the simple answer." He pointed out that drug companies spend less on pet medicines and get a smaller return. And far fewer people buy health insurance for pets than for their families.

"It's the nature of the profession," he said.

Michael Blackwell, a veterinarian and former deputy director of the FDA's Center for Veterinary Medicine, says there is pressure from the pharmaceutical industry, the general public and Congress "to not inhibit the movement of products."

"It is not a very complicated reason for why things look the way they do," he said.

So how big of a sample size would be adequate?

Blackwell, who is now a senior official at the Humane Society of the United States, said there's no universal answer, no one-size-fits-all.

In many cases, it's a cost-benefit trade-off. Short drug trials increase risk, but long trials, particularly in human medicine, could delay life-saving medicines from reaching the market for years.

So the FDA has to weigh the costly search for side effects against the potential benefits of any given drug. More side effects may be tolerated, for example, in a drug used to relieve late-stage cancer symptoms in humans than, say, to control weight or prevent hair loss.

Pet medicines get a lower priority, Lachenbruch said, because "the loss of an animal, a pet, is not considered as serious as loss of a human life."

Drug companies resist disclosure

On May 1, Surtani added Sesame's name to the growing list of deaths that pet owners reported in connection with Trifexis. He called Elanco, which employs veterinarians to answer questions and take product complaints from the public.

He explained what happened to Sesame. Elanco said it was unable to determine what caused Sesame's death. The company said that a veterinarian had not studied tissues to determine whether Sesame had been suffering from a disease or whether poisons were present.

Elanco forwarded an "Adverse Drug Experience Report" to the FDA.

By November 2013, the FDA had collected reports of more than 700 dead dogs — equivalent to 20 dogs per month since Trifexis hit the market in January 2011. Thousands of reports of other side effects, from vomiting to seizures, also came in.

And that wasn't the whole picture. FDA officials told The Star that for every adverse event reported, nine or 10 might go unreported.

The FDA said it "continues to closely monitor" the reports on Trifexis. It declined to say whether it had launched a formal investigation.

It's not as if Trifexis is a clear outlier when it comes to side effects.

Some examples include:

• Deracoxib, the ingredient in Deramaxx, a medicine made by Novartis for pain and inflammation, has been reported in connection with more than 1,100 deaths, 1,660 cases of anorexia and 2,200 cases of vomiting in dogs.

• Carprofen, the active ingredient in the anti-inflammatory drug Rimadyl, made by Zoetis, has been reported in connection with more than 2,000 dog deaths.

• Melarsomine, the ingredient found in Immiticide, a heartworm treatment made by Merial, has been reported in connection with more than 270 cases of collapsing and 540 deaths.

And no one is tracking the side effects of some drugs commonly used by veterinarians. Vets, like doctors, are free to prescribe whatever medicine they choose, and many turn to human drugs, such as the painkiller tramadol and the seizure medication gabapentin.

At the University of Minnesota's animal hospital, veterinarians go through thousands of doses a month of tramadol, said Conzemius, of the university's Clinical Investigation Center. The FDA does not track adverse events for animals using tramadol.

"I have more concern about drugs that are completely unregulated and we just use them," Conzemius said.

But even for animal drugs in the database, the FDA and drug companies say it's tough to draw conclusions. Without knowing how many doses were sold, a number known as the denominator, it's impossible to tell which drug has the higher rate of complaints and might be more dangerous.

"When it comes to epidemiology, if you don't know the denominator, you don't know anything," said Petersen, the Iowa researcher.

Carprofen offers a good example. It has almost three times as many death reports as the ingredients in Trifexis, according to the latest information available. But carprofen has been on the market since 1997, and Trifexis for only three years.

Yet drug companies resist disclosure of that information, no outside group is collecting it, and the FDA says it lacks the authority to demand it.

In a spot check, The Star contacted five large makers of animal drugs. All but one refused to say how many doses it had sold, citing competitive reasons.

Elanco, in a rare industry departure, acknowledged that it has sold more than 70 million doses of Trifexis in the U.S.

Some call on Congress to act

Nearly a year after his dog died, Surtani still puzzles over what killed Sesame.

"There were no abnormal labs," he said. "No abnormal masses. No bleeds. No heart problems. Nothing on an X-ray. How does a dog just die?"

The family has buried Sesame in the backyard, behind the swing set and slides that he used to romp on with the boys.

The grave is marked by a small metal sculpture of a dog — its tail up, eyes bright and tongue out, wanting to play.

Elanco said deaths and other reported reactions to Trifexis may be related to an underlying disease, or perhaps to using other drugs at the same time.

And thousands of veterinarians continue to prescribe and administer Trifexis at more than 10,000 clinics across the country, Elanco says.

But in an industry marked by higher risks and more secrecy than human medicine, who's to know for sure?

It would take an act of Congress to require pharmaceutical companies to report dosage sales of animal drugs. Some say it would be worth the effort.

"I think the public has the right to know a lot more about the drugs that are being marketed," said Blackwell, the former FDA official. "… Any legislation that is going to open up the books so the public can make informed choices is always going to be helpful."

Petersen, the University of Iowa professor, agreed that the denominator problem is serious enough that Congress should step in and require the companies to release the sales information.

For Surtani, until the pharmaceutical industry drops its secrecy and makes the testing process more rigorous, he will always wonder whether pet medicines are safe. To him, the experience also raises broader questions: How much does society value pets? And how much protection do pet owners have a right to expect?

"Some people treat their animals like we do, like they're family," he said. "But to others, they're more of a commodity or toy. From what I've seen, the pharmaceutical industry preys on that. If something goes bad, people will just get another, new dog."

Drug companies have long fought the release of information that could shed more light on the safety of the pet medicines they produce.

Even as institutions in human medicine were teaming up with the U.S. Food and Drug Administration to find creative ways to determine the safety of drugs already on the market, the pet health industry declined to take similar steps.

In 2008, shortly after the painkiller Vioxx was pulled from the human drug market because of safety concerns, the FDA saw the need to gather more information about drugs already on the market.

It approached hospital systems, medical schools, research centers and insurance companies and persuaded them to share data on how people react to medications and treatments.

The program, known as Mini-Sentinel, has helped the FDA keep tabs on about 4 billion pharmaceutical dispensings, more than 4 billion patient encounters with health providers and 350 million "person-years" of patient observations. The FDA says it has greatly improved its understanding of drug safety.

But pet medicines? The group of medicines with the greatest risk of unforeseen side effects? They are not part of Mini-Sentinel. Most of the big players — including major veterinary hospital chains, pet insurers and a network of veterinary schools and clinics — refused to participate.

Some said their data systems were proprietary. Others said they saw "no compelling business reason" to participate.

And some just "were reluctant to cooperate voluntarily with the government or FDA if they were not required to do so," according to a 30-page FDA report.

'Almost clients of the agency'

At the same time, most of the major pet drug companies have pushed the FDA to speed up the review process and keep it that way.

About a decade ago, the drug companies started paying millions of dollars a year in "user fees," under a new law that helped cut the time it takes to review a new animal drug from 295 days to 180.

Today, user fees account for about 14 percent of the FDA's budget for overseeing animal drugs and feed — up from less than 6 percent in 2004 — allowing the FDA to beef up its reviewing staff. The agency has estimated that the industry will pay about $23.6 million this year.

Some health experts see the balance of power shifting, suggesting it is bad for public health.

"Rather than being a regulated industry, these (pharmaceutical companies) are almost clients of the agency," said Dr. Michael Carome, a physician and former associate director for regulatory affairs at the U.S. Department of Health and Human Services.

Industry has become far "too cozy" with regulators, said Dr. Carome, who is now director of the Health Research Group at Public Citizen, a consumer-rights advocacy group based in Washington.

And industry isn't letting up the pressure.

When the law was up for its second reauthorization, officials from five big pharmaceutical companies (Elanco, Bayer, Abbott, Merial and Pfizer), along with trade industry officials, entered lengthy closed-door negotiations with the FDA.

According to minutes of eight meetings in 2012,the industry group stated its case: It was still taking too long and costing too much to approve new animal drugs. The industry repeatedly raised the topic of an "expedited review" and a "shorter review clock."

Call Star reporter John Russell at (317) 444-6283 and follow him on Twitter @johnrussell99

Inconvenient data

The U.S. Food and Drug Administration maintains an Adverse Events Database to give pet owners insights into the drugs prescribed to their animals. But it isn't easy to navigate or understand.

First, the reports are listed by the active ingredients in each drug, not the brand name. Don't bother looking up Trifexis. It won't be listed. You have to look up spinosad and milbemycin oxime.

Second, you find row after row of adverse events reported, from fever to blindness. But they are often broken down into narrow categories, such as "death," "death by euthanasia," "stillborn death" and "newborn death," requiring readers to add up column after column of numbers to get a broad picture.

Third, the Web page hasn't been updated since April 2013. That means thousands of reports, including an untold number for recently launched drugs such as Trifexis, are missing.

PETS AT RISK team

John Russell examined thousands of pages of documents and conducted dozens of interviews for this story. He has written about business and government for The Star since 2005, winning more than 40 awards, including Indiana Journalist of the Year.

Steve Berta, editor on the project, is The Star's Senior Content Coach, handling investigations and narratives. The Ohio University graduate has been a reporter, business editor, editorial writer and newsroom manager over a 35-year career.

Robert Scheer, a Star staff photographer since 1998, received a bachelor's degree in biology from Humboldt State University. His photojournalism work has taken him to Iraq, Greece, Brazil, Mexico and Canada.