TOO MUCH MEDICINE

thebmj.com ЖЖ Feature: Preventing overdiagnosis: how to stop harming the healthy (BMJ 2012;344:e3502) ЖЖ Feature: Female sexual dysfunction is a real but complex problem (BMJ 2010;341:c5336) ЖЖ Feature: Merging of marketing and medical science: female sexual dysfunction (BMJ 2010;341:c5050) EVENING THE SCORE ON SEX DRUGS? The quest to find a “female Viagra” has reached new heights. Ray Moynihan questions a feminist- led campaign to get a rejected drug licensed

thrice failed antidepressant is “Even the Feminist campaign? at the centre of a new market- Score is a slick The Even the Score website is light on detail ing campaign to win approval pharmaceuticals about who initiated the campaign and who’s for what could become the campaign running it, stating simply that it “was created” world’s first blockbuster sex pill masquerading as a voice for American women who wanted to Afor women. Frustrated by the drug’s repeated level the playing field around sexual dysfunction as a grassroots rejection, proponents have orchestrated a fierce feminist treatments. But according to the woman chair- attack, accusing the regulator of unfairness, and movement,” ing the campaign, Susan Scanlan, Sprout Phar- enlisting support from several well connected maceuticals was central to its genesis. She was Cynthia Pearson women’s organisations in the US. Critics coun- approached by Sprout over a year ago, before the ter that the campaign is exceedingly mislead- sex equality, but it has a narrow focus as well: it most recent FDA rejection of flibanserin in 2013. ing, that it targets a desire disorder that does not calls on the FDA to act for women “by approving “They were trying to educate,” she told The BMJ. exist, and that approval could see widespread the first-ever drug to treat the most common form Scanlan was long time chair of the National overprescribing of a drug with marginal benefits of women’s sexual dysfunction.” Without using Council of Women’s Organisations, a network and real safety concerns. the drug’s name, it’s a demand for the regulator of over 200 US organisations. “I’ve spent my A few months ago a website called Even the to approve the thrice failed antidepressant fli- life looking at inequities, including in women’s Score emerged (www.eventhescore.org) attack- banserin, currently being pushed for hypoactive health,” she said, so the approach from Sprout ing the United States Food and Drug Adminis- sexual desire disorder— a now obsolescent diag- “spurred quite a bit of interest.” After looking tration with the claim, “Men outscore women 26 nosis—by new drug company Sprout, a key spon- into it and consulting with trusted colleagues to 0 when it comes to FDA approved treatments sor of the campaign. Sprout is run by a group of she decided to chair the campaign. “I sincerely marketed for Sexual Dysfunction.” The argument experienced pharmaceutical and investment believe, based on fairness, women are not get- is that men have sildenafil and a host of other specialists who reportedly bought flibanserin ting a fair shake.” drugs, but women have none. And according to in 2011 and, according to the business press, Another group approached by Sprout has Even the Score’s website, 43% of women experi- have raised tens of millions of dollars from pri- come to a different conclusion. “Even the Score ence sexual dysfunction. The campaign uses the vate investors with the hope of delivering a new is a slick pharmaceuticals campaign masquer- broad feminist language of rights, choice, and “global brand.”1 ading as a grassroots feminist movement,” NEW VIEW OPPOSITION Leonore Tiefer (left), the sex therapist who initiated the New View campaign to oppose the medicalisation of women’s sexual problems in 2000, is alarmed about this latest company backed campaign. “Even the Score is hijacking feminist language of choice and fairness,” Tiefer says. “It’s disrespectful of the FDA, it’s insulting to feminism, and it misleads the public.” Tiefer wrote a long letter to the president of the National Organization for Women, Terry O Neill, one of the women featured on the Even “Even the Score is the Score website, offering to meet and discuss the issues, but hijacking feminist Tiefer got no reply. She has also launched a petition against the language of choice and campaign (www.ipetitions.com/petition/end-deceptive-pr-about- Men outscore women 26 to 0 for FDA approved fairness” womens-sexual-health). treatments for sexual dysfunction claim campaigners

14 25 October 2014 | the bmj TOO MUCH MEDICINE

says Cynthia Pearson, executive director of PREVALENCE OF 43% IS A WHAT ARE THE APPROPRIATE the National Women’s Health Network, which DISCREDITED FANTASY OUTCOME MEASURES? has written to the FDA supporting its repeated The claim by Even the Score that 43% of Later this month the FDA will host rejection of flibanserin. The network, which does women have sexual dysfunction has long been a two day workshop on “patient- not take money from drug companies, is not discredited. It comes from an old survey that focused drug development” opposed to drug treatments but wants them to asked women whether, over the past year, there for women’s sexual difficulties, be safe and effective. “This is a marketing cam- was a period of several months or more when exploring how best to diagnose and paign, not a science based effort,” says Pearson. they lacked interest in sex, felt anxious about treat them. In particular, the meeting “Sprout is trying to find a way to gets its product sexual performance, were unable to orgasm, will revisit the ongoing scientific approved when it didn’t pass muster via the sci- came to orgasm too quickly, had trouble getting controversy over what should be entific process.” aroused, experienced pain on intercourse, the most appropriate outcome measures in or just didn’t find sex pleasurable. If women clinical trials. Drugs keep failing to meaningfully Thrice failed drug answered yes to just one of these seven, they beat placebo on the key measure of “satisfying Flibanserin originally failed to work out as a were classified as having a sexual dysfunction. sexual events”—testosterone and sildenafil both potential antidepressant back in the early 2000s. Former director of the Kinsey Institute John failed before flibanserin. But if researchers use The drug, then owned by Boehringer Ingelheim, Bancroft says the 43% have dysfunction claim a range of questionnaires to measure women’s was later tested for treatment of so called hypo- is outrageous and that “it doesn’t stand up experience it’s much easier to show some kind 11 active sexual desire disorder, which was claimed scientifically.” Reductions in sexual interest of benefit—for example, a slight movement up to affect 1 in 10 women.2 After closely analysing or other problems are often healthy adaptive or down on a certain scale. This is unsurprising the evidence about flibanserin and hearing testi- responses and “an understandable reaction given that drug companies often fund the mony from a range of sources, in 2010, an advi- to adverse conditions in the relationship . . . or development of these measurement tools and sory committee to the FDA voted unanimously in the individual’s general life situation,” he company linked researchers often design them, to reject it because of a lack of clear benefit and says. Even the lead author on the paper which as was the case with the widely used female serious safety concerns.3 Most of the 11 commit- first featured the 43%, Ed Laumann, professor sexual function index. of sociology at the University of Chicago, is tee members were women. Soon after, the FDA At an industry funded meeting in Paris in 2009, concerned the figure has been misused. “I don’t took the committee’s advice and rejected the Anita Clayton (above) and other colleagues think that these things are medical dysfunctions drug. It failed a third time in 2013, when the FDA with financial ties to drug makers unveiled a in the sense that they should require active knocked back Sprout’s application for approval,4 plan to persuade drug regulators to start relying interventions.” 7 and the company and the FDA are currently in more heavily on these kinds of questionnaires, negotiation over the drug’s future. John Bancroft giving them at least equal weight to “satisfying sexual events.” This strategy, she told the Company funded evidence in 2010 showed says the 43% have 2009 conference, should lead to “improved that at best, compared with placebo, the drug dysfunction claim ability to demonstrate efficacy when such an might offer less than one extra “satisfying sexual is outrageous effect exists.” The demand appears to be that event” a month, and an FDA analysis found nei- and that “it industry and their financially linked researchers ther of the two pivotal studies “met the agreed- doesn’t stand up provide both the products, and the main tools to upon criteria for success in establishing the scientifically” measure the success of those products. efficacy of flibanserin.” The analysis also found common side effects included nausea, dizziness, fatigue, sleepiness, and sedation, causing almost CEO PREVIOUSLY ACCUSED 15% of women taking flibanserin to drop out of OF MISLEADING PROMOTION clinical trials.3 Moreover, the trials showed an In 2010 the FDA sent a warning letter about increased frequency of rare but serious adverse misleading promotion of a testosterone events, including depression, unintentional product to Robert Whitehead, then of Slate injury, and fainting. Pharmaceuticals, currently chief executive of A more recent 2013 study similarly found Sprout. 12 The letter outlined how Slate promoted that premenopausal women taking flibanserin unapproved uses for the drug, omitted or had one more “satisfying sexual event” a month minimised important risk information, broadened than those in the placebo group and recorded indications, overstated efficacy, and presented Cindy and Robert Whitehead a marginal advantage on questionnaire items unsubstantiated superiority claims. The letter Score Coalition, including the nine inaugural about desire of 0.3 on a five point scale.5 Of seven noted that the FDA was “extremely concerned by organizations, signed their support on the named investigators, three were drug company the breadth and scope of violations,” and that the basis of the following statement pasted here employees and two were company consult- company had committed to immediately cease from the website: As supporters of the Even the ants; the study and its write up were company using the promotional materials. Score campaign, we believe that women have sponsored, and a global PR firm helped write up Asked about this matter, and a range of other the right to make their own informed choices results. We know sponsored trials are far more questions about their investments, their role concerning their sexual health; that gender likely to find favourable results for the sponsors’ in Even the Score, and who they were paying equality should be the standard when it comes product,6 so these marginal benefits could prove as consultants, Sprout’s president Cindy to access to treatments for sexual dysfunction; even smaller in independent studies. In addi- Whitehead declined an interview, instead and that the approval of safe and effective treatments for women’s sexual dysfunction tion, over a third of women experienced some releasing a statement to The BMJ: “Sprout, along with the 21 other organizations in the Even the should be a priority for action by the FDA.” form of side effects, which included sleepiness, the bmj | 25 October 2014 15 TOO MUCH MEDICINE

dizziness, nausea, fatigue, and upper respiratory BMJ, but in a recent article she disclosed that in tract infection. One in 25 women experienced the past five years she has consulted to more than adverse events described as “severe.” 20 companies, including Sprout. 10 The BMJ was also unable to speak directly Promoting a drug for a condition that “doesn’t with the consultant Audrey Sheppard, though exist any more” she responded through a third party by refer- The condition that the drug is supposed to treat, ring The BMJ back to Scanlan and Sprout’s pub- hypoactive sexual desire disorder, is a highly lic relations company, Edelman. Scanlan said controversial diagnostic construct.7 Although she did not know who was paying Sheppard to desire problems are real, and can be debilitat- help organise the Even the Score campaign but ing, the idea of a common disorder of desire is that it was “absolutely possible” she was being now discredited. In fact the construct has been paid by Sprout. Asked why she was chairing a removed from the latest edition of the Diagnostic campaign implicitly calling for the approval of and Statistical Manual of Mental Disorders, DSM- a sponsor’s drug, Scanlan was clear: “I do not 5.8 DSM-5 includes a new construct called sexual support a particular drug, but if this [flibanserin] interest/arousal disorder, designed to more accu- goes down,” she said, “all the other drugs in the rately reflect the complexity of women’s sexual pipeline, that’s going to stop, research will stop. experience. With much stricter diagnostic crite- I do believe this is a problem.” ria, prevalence estimates are likely to be a frac- Sprout representatives also met several times tion of the 10% claimed for hypoactive sexual with the National Women’s Health Network desire disorder. The changes are in part designed but failed to persuade its members to support to “reduce the likelihood of overdiagnosis” says flibanserin. On the contrary, the network joined the American Psychiatric Association, “and dis- several other health organisations, writing a tinguish transient sexual difficulties from more strongly worded letter to FDA supporting their

persistent sexual dysfunction.”8 WILLETT MALCOLM evidence based evaluation and rejection of fli- A key member of the working group that rec- A lack of spontaneous desire banserin. “The problem with flibanserin” said ommended the change was Canadian researcher may in fact be normal for the the letter “is not gender bias at the FDA but the and psychologist Lori Brotto, who reviewed the majority of women drug itself.” Pearson explained to The BMJ “the relevant scientific literature. She concluded concept of Even the Score resonates in the heart that a lack of spontaneous desire may in fact Conflicted informants of every woman who has ever felt things aren’t be normal for the majority of women, many of When I put these criticisms of Even the Score to its quite fair. That sense of injustice is real, but it is whom very much enjoyed their sex lives, and chair, Scanlan stressed that she was not a medical misused so badly by this campaign.” that it “should not be pathologised.”7 Another expert or statistician, adding, “I am an ignoramus For almost 20 years drug companies and a member of the working group that produced the when it comes to chemical issues.” She said that small cohort of their paid researchers have used new DSM-5 definitions puts it more bluntly. “It when deciding whether to get involved with Even the absurd claim that almost half of women doesn’t exist any more,” says Cynthia Graham, the Score, she had relied heavily on advice from have female sexual dysfunction to create the “there is no disorder of desire.” others, chiefly an organisation called the Ameri- appearance of massive “unmet need” for drug A senior lecturer in psychology at the Uni- can Sexual Health Association (ASHA), which is treatment (see box on 43%). Paradoxically such versity of Southampton, research fellow at the named on the website as a supporter. “I sat down hyperbole undermines attempts to describe Kinsey Institute, and editor in chief of the Journal with ASHA, and they said yes, this is legit.” Also and prevent the genuine problems of the much of Sex Research, Graham is alarmed by what she informing Scanlan’s decisions to support the cam- smaller group of women for whom a medical has seen on the Even the Score website, includ- paign were meetings with patients with sexual dys- diagnosis may be necessary and for whom a safe ing the discredited claim that 43% of women function. Asked who had arranged those meetings, and effective treatment might prove helpful. It’s experience sexual dysfunction. “They are put- she named ASHA and Sprout. Another source of still unclear whether Even the Score will succeed ting out information that is exceedingly mislead- guidance, Scanlan said, was a group of researchers in bullying the FDA to approve flibanserin. If it ing . . . it’s like propaganda,” she says. Asked who have been paid advisers to Sprout, including does, and marketing goes into overdrive, not about the claim that the regulator is being unfair, psychiatrist Anita Clayton. Asked who was doing only may millions of women be overdiagnosed she says that in this case, “the FDA has no case to the leg work and organising Even the Score, she and overtreated at great cost and untold harm, answer. There is no suggestion on the Even the identified a consultant called Audrey Sheppard, a new low in corporate regulator bashing will be Score website that there have been medications who she said was well informed and had also set, and the future of evidence based drug regu- for women submitted to FDA and not approved, “steered” her. lation will be under threat. for good reason.” She argues the benefits of In virtually every case, the advice that has con- Ray Moynihan senior research fellow, Bond University, diagnoses and drugs are being exaggerated and vinced a long time feminist to lend her credibility to Robina, Australia the importance of education and reassurance this campaign was from sources with financial ties [email protected] about sexual difficulties played down. She’s to drug companies, or from people paid by Sprout. Competing interests: I have written widely about medicalisation, including a book called Sex, Lies and most worried about the long term safety of the A close look at the annual financial accounts of Pharmaceuticals. antidepressant flibanserin—being promoted as ASHA shows that it receives substantial propor- Provenance and peer review: Commissioned; externally a once a day drug—and the potential for over- tions of its funding from drug and device makers peer reviewed. prescribing. “My concern is many women will and companies running clinical trials.9 Clayton did References are in the version on thebmj.com get a diagnosis and medication they don’t need.” not respond to a request for an interview with The Cite this as: BMJ 2014;349:g6246

16 25 October 2014 | the bmj