Victoria Hampshire, Lester Crawford, and ProHeart 6

ProHeart 6

ProHeart 6 (also known as moxidectin) is an injectable sustained-release drug that is manufactured and marketed by Wyeth, a pharmaceutical company, to treat canine heartworm disease for 6 months. ProHeart 6 was launched in June 2001 by Wyeth's subsidiary, Fort Dodge Animal Health (FDAH). By June 2004, 17.1 million doses were sold.

FDA and ProHeart 6

Victoria Hampshire's Concerns

Dr. Victoria Hampshire was the United States Food and Drug Administration's (FDA) Center for Veterinary Medicine (CVM) Adverse Drug Coordinator assigned to monitor the adverse drug events (ADE) reports of ProHeart 6 sent in by both consumers and veterinarians. She found that reports of ADE for ProHeart 6 were unusually high in their "severity, frequency, and similarity of timing of events". From June 1, 2001 to September 1, 2004, there were 5659 reports of ADE and 485 reports of dog deaths that were "possibly, probably, or definitely related" to the use of ProHeart 6. In the same time period, there were 1820 reports of anaphylaxis/anaphylactoid reactions, 378 reports of convulsions, 65 reports of liver lesions, 124 reports of thrombocytopenia, and 67 reports of anemia. From July 1, 2001 to June 30, 2004, the annual number of initial ProHeart 6 ADE did not decrease and the annual number of reported deaths increased. In November, 2003, Dr. Hampshire raised the issue internally, but received little response, despite agreement among other safety officers at the CVM. In July, 2004, distraught consumers brought attention to ProHeart 6's ADE, which caught the attention of Dr. Stephen Sundlof, Director of the CVM. Dr. Sundlof invited Dr. Hampshire to present her findings to the CVM, which caused Dr. Sundlof, to take the matter to Acting FDA Commissioner, Dr. Lester Crawford. In September, 2004, the FDA requested that Wyeth recall ProHeart 6 from the market "pending a review by an independent scientific panel" and they agreed.

Wyeth Fights Back

Shortly after the recall of ProHeart 6, the FDA granted Wyeth's request for a Veterinary Medicine Advisory Committee (VMAC) meeting and scheduled it for January 31, 2005. The timing of the meeting would allow Wyeth a chance to reintroduce ProHeart 6 for the spring heartworm season if the VMAC voted to support its return to market. Thomas Corcoran, President of FDAH, coerced Dr. Sundlof to give him all records of Dr. Hampshire's presentation on ProHeart 6. FDAH asked Dr. Larry Glickman to conduct an "epidemiological study to determine the incidence of potential adverse events associated with ProHeart 6 and to compare these with the safety profile of 2 oral, monthly heartworm preventatives and vaccines".

Wyeth hired Germinder & Associates, Inc to investigate Dr. Hampshire, without her knowledge, for conflict of interest in her post-market review of ProHeart 6. Private agents found a website through which Dr. Hampshire prescribed ProHeart 6's competitors. They attempted to procure competitor heartworm products through the website, but failed because Dr. Hampshire didn't prescribe them. They instead, purchased over-the-counter drugs and saved the purchase records.

On November 19, 2004, Robert Esner, CEO of Wyeth, met with Dr. Crawford to present Wyeth's evidence of their allegations against Dr. Hampshire for conflict of interest. Robert alleged that Dr. Hampshire promoted rival drugs of ProHeart 6 and that made her biased towards it. Furthermore, they claimed Dr. Hampshire pursued the withdrawal of ProHeart 6 for personal financial gain. Dr. Hampshire had no knowledge of this meeting.

Wyeth attempted to discredit Dr. Hampshire beyond the FDA to the veterinary community. A sales representative stated that Dr. Hampshire pursued the withdrawal or ProHeart 6 for personal financial gain and that received $70,000.

Lester Crawford Removes Victoria Hampshire

On January 7, 2005 the Commissioner of the FDA, Lester Crawford, reassigned Victoria Hampshire to another position in the FDA. There was no explanation for her reassignment. This meant that she was officially removed from the ProHeart 6 case as well as all other adverse drug event cases. Dr. Hampshire was subjected to an internal criminal investigation by the FDA for alleged misconduct and conflicts of interest. During her reassignment, she was told not to attend the upcoming VMAC public meeting.

ProHeart 6 Deemed Unsafe

On January 31, 2005, ProHeart 6 was recalled by the FDA in an 8–7 vote by VMAC. It was shown that certain processes in the manufacturing of ProHeart 6 resulted in some adverse drug events. The results of Glickman's study suggest that the incidence of ADE following administration of ProHeart 6 was comparable to 2 oral, monthly heart-worm preventatives, despite the fact that nearly 5,500 reports of ADE followed the use of ProHeart 6 were submitted to the CVM at the time of his study. The voters that voted "no," agreed that more study was required on the drug. The voters that voted "yes," were disagreed on the sufficiency of the study, but agreed that further study should be conducted while the drug was in the market.

Senator Charles Grassley Investigates

Dr. Hampshire held an inactive pharmacy account through which she prescribed drugs to old clients, friends, and family. She estimated that she wrote 14 prescriptions per year and made less than $200 over the course of two years. This information was fully disclosed and purchases went to the associated pharmacy.

Conclusion

A vote to remove ProHeart 6 resulted 8–7 in favor. All charges against Dr. Hampshire were removed. For her part in the blowing the whistle on ProHeart 6 and staying true to her profession, Dr. Victoria Hampshire was selected as the veterinarian of the year in 2006.

Professionalism

Dr. Hampshire's duty was to conduct investigations if any adverse events appeared in animal drug use reports. Dr. Crawford faced a tough decision to either fire Dr. Hampshire for Wyeth's report on her conflict of interest, with the website, or reassign her. Dr. Crawford made the safe decision on reassigning her, however the emotional impact this had on Dr. Hampshire was enough to make his decision seemed morally wrong. The lack of explanation and the investigation also seemed excessive, considering that Dr. Hampshire was doing her job correctly. However, Dr. Crawford could jeopardize the credibility and reputation of the FDA if he had not conducted the investigation and Dr. Crawford was guilty of Wyeth's allegations. The lack of explanation may have been to maintain the investigation. Wyeth naturally wanted to maximize revenue; such an act of finding evidence leading to Dr. Hampshire's conflict of interest was understandable. It was the culmination of each participant's duties that resulted in an emotional story.

Lessons

"If you do your job right and you're questioned, you lose your job [for now]" - Dr. Linda Tollefson, past deputy head of FDA's center for Veterinary Medicine.Tollefson was quoted after realizing Dr. Hampshire was reassigned for doing her duties as AEC. This conveys Tollefson's pessimism saying that good people get punished, but naturally one may feel pessimistic when finding news such as Dr. Hampshire's reassignment. The [for now] is added to this quote to use a property of karma; doing good eventually gives good. Dr. Hampshire worked for a more suitable job after some period. This may show that if you listen to the "click" in your head,you will find that your job eventually aligns with your happiness.

This lesson can be applied to college students majoring in their passion. Some parents say to study a subject their child likes. They say in the end a happier life is fulfilled if people do what they love. Contrast this with stereotypical parents who want their child to become a doctor, lawyer, engineer but the child wants to pursue another subject. Finding out later in life that their job does not bring happiness versus a child who pursued their passion may pay off for the latter child who went against their parent's desires, took risks, and achieved lesser goods.

Who pulls the strings? Even though Dr. Crawford ultimately made the decision to reassign Dr. Hampshire, outside influences may have swayed his choice. Wyeth's attack against Dr. Hampshire in revealing possible conflicts of interest due to her personal website may have been a red flag for Dr. Crawford. This evidence was used as leverage. It is important to know all participants involved in a decision. Like the soccer ball analogy, see who is on the "same team" in controlling the ball (Dr. Crawford).

Who pulls the strings can be applied to milk as discussed in class. The message "Milk does the body good" is advertised, and there is science to back up the benefits of vitamin D which may convince many that milk is great. It is healthy to drink milk every day, say some nutritionists, however some studies suggest that people who drink three or more glasses a day versus less than one are twice as likely to die. Who works behind the scenes of milk may be the lobbyists, farmers, and businesses that depend on milk for their own benefits.