UCSF Marketing of Medicines Course
Principal Investigator: Lisa Bero, PhD
PRACTICE PROBLEMS
Industry-sponsored Research and Marketing
by Thomas B. Newman, MD, MPH
1. An industry-sponsored randomized double-blind trial of 1573 patients with herpes
simplex labialis in 31 U.S. ambulatory clinics compared 1% penciclovir (Denavir®) cream to
placebo, both applied q 2 hr while awake.(1) Healing was significantly faster with
Penciclovir (P<0.001). There was no significant difference in adverse effects.
a. What more do you need to know before prescribing the medication for this
indication.?
2. A Merck-sponsored randomized, double-blind trial compared montelukast (Singulair®) 4
mg/day to placebo for children with asthma. The study enrolled 689 children from 93
centers on 5 continents. Montelukast was superior to placebo (P=0.003); the difference
was 0.12 points on a 6 point composite symptom score.(2)
a. Why do you think they used so many centers for a common illness like asthma?
b. Do you think the results are clinically significant?
c. There was no difference in the frequency of hospitalizations for asthma between
the two groups, but the montelukast group had a lower risk of needing rescue with
steroids (19% vs 28% over 12 weeks). What is the Number Needed to Treat for
12 weeks to prevent one child from needing a course of oral steroids?
d. Singulair® costs about $4 per pill. How much does it cost to prevent one course
of steroids?
UCSF Marketing of Medicines Course
Principal Investigator: Lisa Bero, PhD
3. A cost-effectiveness analysis of Respiratory Syncytial Virus Immune Globulin (RSV-IG)
assumed that the decrease in hospitalizations observed in a randomized trial would translate into
a decrease in mortality, then estimated the cost per quality-adjusted life year. However, rather
than considering only the life expectancy of the child, they took a new approach, considering
subsequent generations as well:
“Patients who do not die in childhood can be expected to produce their own children, who, in
turn will produce future generations of offspring…We must value the life expectancies of the
dead child's potential children, potential children's children, and so on, ad infinitum…”(3)
a) Who do you think sponsored this study?
b.) How would this cross-generational approach affect their results?
c.) What do you think about it?
4. A randomized, double-blind trial compared diphenhydramine 50 mg t.i.d. with
desloratadine (Clarinex®) 5 mg q.d). and placebo for relief of symptoms in 610 patients
with moderate-to-severe seasonal allergic rhinitis (hay fever). Relative to the placebo
group, the reduction from baseline in symptom scores was 77.6% with diphenhydramine
(P<0.001) and 21% with desloratadine (P=0.12). Somnolence occurred more frequently
with diphenydramine (22.1%) than with desloratadine (4.5%) or placebo (3.4%).(4)
a. Who do you think sponsored this study?
b. How could they do this as a double-blind study when diphenhydramine was 3
times a day and desloratadine was once a day?
c. What do you think about the doses of medications used?
UCSF Marketing of Medicines Course
Principal Investigator: Lisa Bero, PhD
5. A recent randomized, double-blind trial compared intranasal and intramuscular flu
vaccines in children 6 months to 6 years old using a double-dummy design. The authors
chose reported "Among subjects being vaccinated for the first time, 57.0% of those
receiving intramuscular placebo and 46.3% of those receiving intranasal placebo had
a runny or stuffy nose within 10 days after vaccination.”
a. What exactly does this mean?
b. Why do you suppose they reported it this way?
c. How did this get past the editors of the New England Journal of Medicine?
6. The meta-analysis of randomized trials that led to the FDA’s black box warning on
antidepressants(5) used a composite outcome, called “suicidality,” which included suicidal
thinking, suicidal behavior (e.g., preparation for suicide) and suicide attempts. (There were no
actual completed suicides in any of the randomized trials.) By far the largest number of
outcomes were from suicidal thinking. The Black Box Warning says: “Antidepressants increase
the risk of suicidal thinking and behavior (suicidality) in children and adolescents with major
depressive disorder (MDD) and other psychiatric disorders.” What do you think about
combining these outcomes into a composite outcome this case? (The effect on suicidal behavior
appeared similar to the effect on ideation, but it was not statistically significant.)
References
1.
2.
3.
4.
5.
Spruance SL, Rea TL, Thoming C, Tucker R, Saltzman R, Boon R. Penciclovir cream for the treatment of
herpes simplex labialis. A randomized, multicenter, double-blind, placebo-controlled trial. Topical
Penciclovir Collaborative Study Group. Jama 1997;277(17):1374-9.
Knorr B, Franchi LM, Bisgaard H, Vermeulen JH, LeSouef P, Santanello N, et al. Montelukast, a
leukotriene receptor antagonist, for the treatment of persistent asthma in children aged 2 to 5 years.
Pediatrics 2001;108(3):E48.
Hay J. Cost effectiveness of RSV Immune Globulin. Am J Managed Care 1996;2:851-61.
Raphael GD, Angello JT, Wu MM, Druce HM. Efficacy of diphenhydramine vs desloratadine and placebo
in patients with moderate-to-severe seasonal allergic rhinitis. Ann Allergy Asthma Immunol
2006;96(4):606-14.
Newman TB. A black-box warning for antidepressants in children? N Engl J Med 2004;351(16):1595-8.