FEDERAL AND STATE GOVERNMENT ACTIONS AND THEIR IMPACT ON DRUG DECISION-MAKERS
After a year of turmoil over drugsafety, critical vaccine shortages,and a clamor to permit importingof unapproved low-cost drugsfrom abroad,FDA faces further upheavalfrom within. CommissionerLester M. Crawford,DVM, PhD, resignedabruptly in September afteronly 2 months in the top spot. His surprisemove has generated considerableuncertainty about the future leadershipof the agency.
The White House tapped AndrewC. von Eschenbach,MD, director ofthe National Cancer Institute (NCI) atthe National Institutes of Health(NIH), as acting FDA commissioner.Dr von Eschenbach told FDA staffmembers that he would work hard toensure a “smooth transition” and tokeep agency efforts “on track.” But hisinitial decision to remain NCI directorwhile taking the helm of FDA drewsharp rebukes from all sides. Legislatorsand patient advocates voiced concernsabout inherent conflicts ofinterest in advocating for speedy accessto new cancer treatments while overseeingthe safety and effectiveness ofthose therapies. In response, Dr vonEschenbach handed over day-to-daymanagement of NCI to a deputy andsaid he would devote his energies tothe work of FDA.
Dr von Eschenbach was a cancerspecialist from the M.D. AndersonCancer Center in Houston,Texas, beforecoming to NCI in 2002, and hehas close ties to the Bush family. Hisrole at NCI has made him a familiarfigure on Capitol Hill. Pharmaceuticaland biotech companies publicly applaudedthe choice of a vocal advocateof speeding needed treatments to patients,as well as someone who is acquaintedwith the FDA approvalprocess through collaborative effortsbetween NCI and FDA. Dr von Eschenbachhas supported joint FDANCIinitiatives to develop and validatebiomarkers and advance personalizedmedicine as part of his campaign totransform cancer into a more manageabledisease by 2015.
At the same time, the new acting FDAcommissioner has little familiarity withthe many complex and critical regulatoryprograms that FDA oversees. Inrecent months, initiatives to spur newtherapies along the critical developmentpath have taken a back seat todealing with daily crises.Congress continues to press formajor changes in how FDA overseesdrug safety, for moreliberal drug importationpolicies, and forinitiatives to ensureadequate vaccine supplies.The debate is farfrom resolved overbroader access to PlanB (the “morning-afterpill”), as well as theregulation of follow-onbiologics.The safetyand testing of implantablemedicaldevices have emergedas serious concerns,and the need to maintain the safetyof the nation’s food supply is a monumentaltask.Dr von Eschenbach’s enthusiasmfor speeding new treatments to patientsfaces objections from a broad range ofpatient advocates who are concernedabout protecting relatively healthy patientsfrom high-risk medications.
FDA officials say they will carry on asusual during the transition to new leadership,as it may take months for theWhite House to appoint-and theSenate to confirm-a permanent FDAcommissioner. Following Crawford’sterse resignation announcement,deputy commissioners Scott Gottlieb,Janet Woodcock, Murray Lumpkin,and Patrick Ronan sent a message toall FDA employees emphasizing theircommitment to the agency and intentionof continuing its important work.But during this uncertain period, itwill be difficult for staff members tomove forward with controversial initiativesor to address fears that drug safetycrises have created a go-slow approachon the new drug approval side of FDA.Many observers say that safety issueshave delayed the approval of some importantnew therapies,and that advisory committeemeetings nowdevote much moretime to discussions ofminor adverse events.
Some critics maintainthat more extensivepre-market testing protocolscould preventpost-approval safetyproblems, but researcherscounter that expandeddevelopmentprograms may not revealthose adverse eventsthat occur in a small number of patientsor that take time to emerge.Drug developmentexperts instead look for strategiesto make clinical trials more efficientby gaining more information from smallernumbers of select study participants.The vague circumstances surroundingDr Crawford’s departure,moreover,may further complicate efforts to secure a permanent FDAleader.
In addition, Senate Democratshave insisted that the new FDA commissionerbe completely free of pharmaceuticalcompany influence. CurrentFDA officials are linked too closely torecent agency missteps to be confirmed.Congress and the HHS Inspector Generalare investigating whether the Senateconfirmation process failed to uncoverimportant information related to DrCrawford’s appointment, which may resultin even more rigorous scrutiny ofany future nominee and could furtherdeter qualified medical leaders fromseeking the job.
FDA WEIGHS DTC ADVERTISING
FDA wants to hear from pharmacistsand other healthcare professionalsabout whether it’s possible to makedirect-to-consumer (DTC) advertisingmore balanced and informative.Theagency is holding a 2-day public meetingNovember 1–2 and has asked all interestedparties-consumers,managedcare plans, drug manufacturers, andhealthcare professionals-to commenton the pros and cons of promoting medicalproducts to the public, whether thereare ways to improve the presentation ofproduct risks, and whether balancedmessages can ever be communicated inTV ads or other media.Concerns that DTC advertisingmay encourage unsafe medication useare prompting critics to urge tighterregulations of consumer-directedcommunications, perhaps by requiringpre-clearance of more promotionalmaterials and stiffening penaltiesfor manufacturers whose materials violateregulations.
Drug advertising has been analyzed,researched, and discussed repeatedlyby FDA in recent years. Last year theagency issued draft guidances for revisingthe “brief summary” in print adsand improving “help-seeking”messages,but these guidances are stillunder review. Manufacturers have petitionedFDA to stop restricting sucheducational messages, while patient advocateshave petitioned FDA to banDTC ads altogether.Parties that want to make presentationsat the meeting in early Novemberwere required to contact FDA by October11, but comments on the proceedingscan be filed through February2006.FDA’s dockets can be accessedat:http://www.accessdata.fda.gov/scripts/oc/dockets/meetings/meetingdocket.cfm
MANUFACTURERS, ONCOLOGISTSBACK OFF-LABEL PRESCRIBING
While public and private health plansand payors seek to curb off-label use ofdrugs to control pharmaceutical spending,pharmaceutical companies andphysicians are highlighting the importanceof flexible coverage policies in providingthe best treatments for cancerpatients.A survey finds that most oncologistsare concerned that Medicare andinsurers won’t pay for off-label use ofanticancer drugs and often change treatmentdecisions as a result.These opinions come from a handfulof oncologists (28) and oncology practicemanagers (12) participating in astudy sponsored by PhRMA (PharmaceuticalResearch and Manufacturers ofAmerica), BIO (Biotechnology IndustryOrganization), and the Association ofCommunity Cancer Centers.The AmericanCancer Society praised the surveyfor highlighting the importance of theoff-label use of drugs and biologics in expandingcancer treatment options.Some oncologists report an increasein the off-label use of cancer therapiesdue to the lag between the publicationof information on new treatments andFDA approval of new indications.Other cancer specialists acknowledge adrop in off-label prescribing, becausesome approved labels are broader andreimbursement is tight.
Recent Medicare coverage decisionshave brought the issue to a head:Whilethe Centers for Medicare and MedicaidServices (CMS) said in January that itwould cover several off-label drugs forcolorectal cancer, a policy issued inApril limited such coverage to thosedrugs that manufacturers are studyingfurther to document unapproved uses.CMS continues to weigh changes in itsoff-label oncology coverage policy, andPhRMA hopes more flexible paymentapproaches will be considered.
EMPHASIS ON ETHICS
Charges of unethical researcher behaviorcontinue to make news, as seen inreports last summer about prominentresearchers receiving hefty fees fromWall Street investment companies totalk about new medical treatments.Although participating physicians andscientists insist that they discuss onlypublicly available information-andnever current research projects-thehigh fees (reportedly more than$1,000 for a half-hour chat) raisedskepticism about such limitations.Senate Finance Committee chairmanCharles Grassley (R-Iowa) calledon the Justice Department and the Securitiesand Exchange Commission(SEC) to investigate whether doctorsare leaking confidential information ondrug research to investment firms.While clinical researchers who discussresearch with investors may not be violatingany laws, such advisory arrangementsappear unethical and often violate confidentialityagreements with sponsors.Pharmaceutical companies and researchorganizations have a stake in halting suchbehavior, as seen in the new ethics rulesadopted by the National Institutes ofHealth (NIH).
The policy prohibits allNIH employees from engaging in paidoutside consulting with pharmaceuticaland healthcare companies and limits theamount of stock that high-level NIH officialsmay own in drug, biotechnology,medical device, or other healthcare companies(up to $15,000 in any single firm).Although NIH director Elias Zerhouni,MD, has said he believes theconsulting ban is necessary to restorepublic trust in NIH, outside scientistsfear that such tight curbs will severelyreduce interaction among public andprivate researchers.
One way to prevent insider informationdisclosure and conflicts of interest isto make more information on clinicaltrial activities and results available to thepublic, as advocated by some membersof Congress and advocacy groups. Moreproposals have surfaced on Capitol Hillthat would require clinical trial sponsorsto post on websites more detailed informationabout early stage research andstudy results.