Pretesting - Number of Completes

Main Survey—Part I

INTRO1 Thank you for agreeing to participate in this study today.

Make sure you are comfortable and can read the screen from where you sit.

This study aims to understand how medical providers interpret promotional materials from pharmaceutical companies such as sales aids or brochures. We are not connected with the drug being promoted.

The survey will take about 20 minutes to complete. We ask you to complete the survey in one sitting (without taking any breaks) to avoid distractions. Your input is extremely valuable.

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INTRO2 On the next screen, you will be shown two pages of a sales aid for a new prescription drug. In the interest of time, you will see only a specific portion of the sales aid and not the full material.

Imagine that this sales aid is for a medication that you might be interested in prescribing to your patients.

Even though the sales aid is on a computer screen, please review it as if you received it from a pharmaceutical representative.

The sales aid has two pages. You can flip between the pages by clicking on the “View Page 1” and “View Page 2” buttons at the bottom of each page. Once you finish viewing the sales aid, please click “Start Next Part of Survey” to move to the next part of the survey.

We will then ask you some questions about the sales aid. These questions focus on the content of the sales aid and are not a test of intelligence.

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[PRESENT SALES AID]

[DO NOT ALLOW RESPONDENTS TO GO BACK TO PREVIOUS PAGES IN THE SURVEY]

[ON TOP OF SALES AID INCLUDE THE FOLLOWING TEXT]

Even though the sales aid is on a computer screen, please review it as if you received it from a pharmaceutical representative.

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PRETEST Were you able to view the image?

1. Yes

2. No [TERMINATE]

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SCRIPT1 We would now like to ask you a series of questions based on the portion of the sales aid you saw.

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ENDPOINT [IF CONDITION=1-10] What clinical endpoint did the chart in the sales aid focus on?

[RANDOMIZE RESPONSE OPTIONS]

3. Overall survival [Correct for DRUGY]

1. Progression-free survival [Correct for DRUGX]

2. Time to progression

3. Objective response rate

[IF CONDITION=11-15] Which one of the following choices is the surrogate endpoint that the chart in the sales aid focused on?

[RANDOMIZE RESPONSE OPTIONS]

7. Decrease in iron load [Correct]

8. Reduction in side effects

9. Improvement in symptoms

10. Increase in objective response rate

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INDICATION According to the sales aid, [IF CONDITION=1-5: XEDALITI + VULPAFEN; IF CONDITION=6-10: XEDALITI in combination with Rd (lenalidomide + dexamethasone); IF CONDITION=11-15: FEXXOPER] is approved to treat patients with which medical condition?

[RANDOMIZE RESPONSE OPTIONS]

[IF CONDITION=1-5]

11. Unresectable or metastatic melanoma patients with a BRAF V600E/V600K mutation [Correct]

12. Refractory BRAF V600E mutation positive-hairy cell leukemia

13. Multiple myeloma patients who have received one to three prior therapies

[IF CONDITION=6-10]

14. Multiple myeloma patients who have received one to three prior therapies [Correct]

15. Treatment-naïve multiple myeloma patients

16. Non-Hodgkin lymphoma patients

[IF CONDITION=11-15]

17. Transfusional iron overload due to thalassemia syndrome [Correct]

18. Transfusional iron overload due to myelodysplastic syndrome

19. Transfusional iron overload due to hereditary hemochromatosis

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REVIEW The following information may or may not have been in the portion of the sales aid you just viewed. Please indicate whether you noticed the following types of information in the sales aid you viewed.

[RANDOMIZE ORDER]	No, I did not notice it 1	Yes, I skimmed it 2	Yes, I read most or all of it 3
REVIEW1A [IF CONDITION=1-5: Limitations of subgroup analysis; IF CONDITION=6-15: Discussion of statistical significance of results]
REVIEW1B Visual display of the data (e.g., chart or graph)
REVIEW1C List of potential side effects
REVIEW1D Complete prescribing information

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ATTEN_DISC The image below has been blurred for the purpose of this question.

[DISPLAY SCREENSHOT OF SECOND PAGE OF SALES AID WITH A BLACK BOX OVER WHERE THE SPECIFIC DISCLOSURE WOULD BE]

Here is an edited portion of the sales aid you just saw. Was there text in the area shaded in black, or was there no text?

20. There was text

21. There was no text

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DISC_FU [DISPLAY SCREENSHOT OF SECOND PAGE OF SALES AID WITH A BLACK BOX WHERE THE SPECIFIC DISCLOSURE WOULD BE] [IF ATTEN_DISC= yes] How closely did you read the information in the black box?

22. I saw it but did not read it

23. I skimmed it

24. I read most or all of it

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DISC_OE [IF DISC_FU = 2 or 3] Please enter anything that you recall reading in the text included in the black box. We understand that it may be difficult to remember details even if you read the information closely. This is not a test. Please just do your best to note what you recall.

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RECOGNITION The following statements may or may not have been in the portion of the sales aid you just viewed. Please indicate whether you recall seeing the following statements in the sales aid, regardless of whether you believe they are true.

[DISPLAY IF CONDITION=1-5. RANDOMIZE ORDER OF SUBITEMS]	Do Not Recall Seeing 1	Recall Seeing 2
RECOGX1 This presentation includes information of uncertain clinical utility and should be interpreted cautiously in making treatment decisions.
RECOGX2 [IF CONDITION= 2 OR 4] In the figure above, a Cox model was used to estimate hazard ratios. [IF CONDITION=3 OR 5] The figure above presents the observed treatment effects in various subgroups by baseline characteristics in the study. [IF CONDITION=1: Randomly assign people to either see the technical or nontechnical sentence]
RECOGX3 A multicenter, randomized, double-blind, placebo-controlled study evaluated the efficacy and safety of XEDALITI + VULPAFEN.
RECOGX4 XEDALITI + VULPAFEN can cause fetal harm when administered to a pregnant woman.

[DISPLAY IF CONDITION=6-10. RANDOMIZE ORDER OF SUBITEMS]	Do Not Recall Seeing 1	Recall Seeing 2
RECOGY1 This presentation includes information of uncertain clinical utility and should be interpreted cautiously in making treatment decisions.
RECOGY2 [IF CONDITION=7 OR 9] Overall survival (OS) was tested hierarchically after the co-primary endpoints. [IF CONDITION=8 OR 10] Overall survival (OS) was a secondary endpoint of this study. [IF CONDITION=6: Randomly assign people to either see the technical or nontechnical sentence]
RECOGY3 A Phase 3, randomized, open-label study evaluated the efficacy and safety of XEDALITI in combination with Rd.
RECOGY4 XEDALITI + Rd demonstrated a similar incidence of adverse events vs Rd alone.

[DISPLAY IF CONDITION=11-15. RANDOMIZE ORDER OF SUBITEMS]	Do Not Recall Seeing 1	Recall Seeing 2
RECOGZ1 This presentation includes information of uncertain clinical utility and should be interpreted cautiously in making treatment decisions.
RECOGZ2 [IF CONDITION= 12 OR 14] These data are derived from an open label, uncontrolled, nonrandomized analysis of preexisting clinical data from 12 studies. [IF CONDITION=13 OR 15] These data are derived from a retrospective analysis of patients from 12 previous studies. [IF CONDITION=11: Randomly assign people to either see the technical or nontechnical sentence]
RECOGZ3 There are no controlled trials demonstrating a direct treatment benefit, such as improvement in functioning or increased survival.
RECOGZ4 There are no studies with FEXXOPER with pregnant women to inform any drug-associated risks.

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[RANDOMIZE PRESENTATION ORDER OF BENEFICIAL AND IMPROVE]

BENEFICIAL Based on the sales aid you saw, how beneficial do you think [CONDITION=1-5: XEDALITI + VULPAFEN; IF CONDITION=6-10: XEDALITI + Rd; IF CONDITION=11-15: FEXXOPER] might be for treating [IF CONDITION=1-5: unresectable or metastatic melanoma patients with a BRAF V600E/V600K mutation, IF CONDITION=6-10: multiple myeloma patients, IF CONDITION=11-15: patients with transfusional overload]?

25. Not at all beneficial

26. Somewhat beneficial

27. Moderately beneficial

28. Very beneficial

29. Extremely beneficial

IMPROVE Based on the sales aid, to what extent do you agree or disagree with the following statement:

I believe [CONDITION=1-5: XEDALITI + VULPAFEN; IF CONDITION=6-10: XEDALITI + Rd; IF CONDITION=11-15: FEXXOPER] improves [IF CONDITION=1-5, progression-free survival of patients. IF CONDITION=6-10, overall survival of patients. IF CONDITION=11-15, a patient’s iron load.]

30. Completely disagree

31. Disagree

32. Somewhat disagree

33. Somewhat agree

34. Agree

35. Completely agree

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EVIDENCE1 Based on the sales aid, to what extent do you agree or disagree with the following statement:

I believe there is strong evidence of [IF CONDITION=1-5: XEDALITI + VULPAFEN’S; CONDITION=6-10: XEDALITI + Rd’s; IF CONDITION=11-15: FEXXOPER’S] benefit to patients.

36. Completely disagree

37. Disagree

38. Somewhat disagree

39. Somewhat agree

40. Agree

41. Completely agree

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EVIDENCE2 How much evidence does the sales aid provide that [IF CONDITION=1-5: XEDALITI + VULPAFEN; IF CONDITION=6-10: XEDALITI + Rd; IF CONDITION=11-15: FEXXOPER] is appropriate to treat [IF CONDITION=1-5: unresectable or metastatic melanoma patients with a BRAF V600E/V600K mutation? IF CONDITION=6-10: multiple myeloma patients? CONDITION=11-15: patients with transfusional overload?]

42. Insufficient evidence

43. Preliminary evidence

44. Strong evidence

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DECISIONS Which one of the following statements best summarizes how you feel about the data presented in this sales aid?

45. The data would not be useful in making prescribing decisions.

46. I would consider the data when making prescribing decisions.

47. I would change my prescribing decisions based on the data.

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[RANDOMIZE PRESENTATION ORDER OF COMPLEX AND CONFUSING1]

COMPLEX How complex was the information presented in the portion of the sales aid you saw?

48. Not at all complex

49. Somewhat complex

50. Moderately complex

51. Very complex

52. Extremely complex

CONFUSING1 How confusing was the information presented in the portion of the sales aid you saw?

53. Not at all confusing

54. Somewhat confusing

55. Moderately confusing

56. Very confusing

57. Extremely confusing

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CONFUSING2 Please think about the average [IF SPECIALTY=1: primary care physician, IF SPECIALTY=2, 3 , 4, or 5: oncologist] in your field. How confusing would he or she find the information in the sales aid you saw?

58. Not at all confusing

59. Somewhat confusing

60. Moderately confusing

61. Very confusing

62. Extremely confusing

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[RANDOMIZE PRESENTATION ORDER OF BELIEVABLE, CREDIBLE, AND BIASED]

BELIEVABLE How believable was the information presented in the portion of the sales aid you saw?

63. Not at all believable

64. Somewhat believable

65. Moderately believable

66. Very believable

67. Extremely believable

CREDIBLE How credible was the information presented in the portion of the sales aid you saw?

68. Not at all credible

69. Somewhat credible

70. Moderately credible

71. Very credible

72. Extremely credible

BIASED How biased was the information presented in the portion of the sales aid you saw?

73. Not at all biased

74. Somewhat biased

75. Moderately biased

76. Very biased

77. Extremely biased

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Main Survey—Part II

[PUT LINK TO SALES AID ON THE TOP OF EACH SCREEN. CAPTURE PARADATA ON WHETHER RESPONDENT CLICKS ON LINK FOR EACH SCREEN.]

SCRIPT2 When answering the remaining questions, click on the link at the top of the page above the question to view the same sales aid you saw earlier.

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P_VIGNETTE Sarah has been diagnosed with [IF CONDITION=1-5: metastatic melanoma with a BRAF V600 mutation. IF CONDITION=6-10: multiple myeloma. She has received three previous therapies and has documented disease progression. IF CONDITION=11-15: thalassemia and has developed iron-overload due to her transfusions. Chelation therapy did not sufficiently reduce her iron levels.]

Based on the information presented in the sales aid, Sarah is a good candidate for [CONDITION=1-5: XEDALITI + VULPAFEN; IF CONDITION=6-10: XEDALITI + Rd; IF CONDITION=11-15: FEXXOPER].

78. Completely disagree

79. Disagree

80. Somewhat disagree

81. Somewhat agree

82. Agree

83. Completely agree

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N_VIGNETTE John was newly diagnosed with [IF CONDITION=1-5: wild-type BRAF melanoma; IF CONDITION=6-10: myelodysplastic syndrome; IF CONDITION=11-15: iron-overload due to myelodysplastic syndrome].

Based on the information presented in the sales aid, John is a good candidate for [CONDITION=1-5: XEDALITI + VULPAFEN; IF CONDITION=6-10: XEDALITI + Rd; IF CONDITION=11-15: FEXXOPER].

84. Completely disagree

85. Disagree

86. Somewhat disagree

87. Somewhat agree

88. Agree

89. Completely agree

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MOREINFO If you had patients with [IF CONDITION=1-5: unresectable or metastatic melanoma with a BRAF V600E/V600K mutation, IF CONDITION=6-10: multiple myeloma who have received one to three prior therapies, IF CONDITION=11-15: transfusional iron overload due to thalassemia syndromes,] how interested would you be in finding more information about [IF CONDITION=1-5: the use of XEDALITI in combination with VULPAFEN; IF CONDITION=6-10: the use of XEDALITI in combination with Rd; IF CONDITION=11-15: FEXXOPER]?

90. Not at all interested

91. Somewhat interested

92. Moderately interested

93. Very interested

94. Extremely interested

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SCRIPT4 For the following questions, if you don’t know the answer or aren’t sure, just take your best guess.

[RANDOMIZE ORDER OF ALL COMPREHENSION ITEMS: THERAPY—PRELIM. PRESENT EACH QUESTION ON A SEPARATE SCREEN]

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THERAPY According to the sales aid, [CONDITION=1-5: XEDALITI + VULPAFEN; IF CONDITION=6-10: XEDALITI + Rd; IF CONDITION=11-15: FEXXOPER] is considered a…

95. First-line therapy [Correct for DRUGX]

96. Second-line therapy [Correct for DRUGY and DRUGZ]

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ANALYSIS_C [IF CONDITION=1-5] According to the sales aid, is this statement true or false?

The subgroup analysis assessed the consistency of the results according to prognostic factors as well as age and geographical location.

97. True [Correct]

98. False

ANALYSIS_E [IF CONDITION=6-10] According to the sales aid, which statement best describes the analysis in the sales aid you saw?

[RANDOMIZE RESPONSE ORDER]

99. Overall survival analysis was conducted at the completion of the clinical trial.

100. Overall survival analysis was conducted before the completion of the clinical trial. [Correct]

ANALYSIS_F [IF CONDITION=11-15] According to the sales aid, which statement best describes the analysis in the sales aid you saw?

[RANDOMIZE RESPONSE ORDER]

101. This analysis used data from other clinical trials that were previously conducted. [Correct]

102. A new randomized controlled clinical trial was conducted to identify patients for this study.

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RESULTS1_C [IF CONDITION=1-5] According to the sales aid, which one of the following statements is true?

[RANDOMIZE OPTIONS 1-3]

103. The benefit for progression-free survival was evident in only a few patient subgroups.

104. Some subgroups significantly deviated from the overall effect.

105. The sales aid reported a statistically significant subgroup–treatment interaction effect.

106. None of the above. [Correct]

RESULTS1_E [IF CONDITION=6-10] According to the sales aid, which one of the following statements is true?

[RANDOMIZE OPTIONS 1 & 2]

107. The interim analysis for overall survival found a positive (but nonsignificant) trend favoring XEDALITI in combination with Rd versus Rd alone. [Correct]

108. The interim analysis for overall survival found a positive and statistically significant trend favoring XEDALITI in combination with Rd versus Rd alone.

109. None of the above.

RESULTS1_F [IF CONDITION=11-15] According the sales aid, which one of the following statements is true?

[RANDOMIZE OPTIONS 1-3]

110. The success rate was achieved for the three indicators of iron overload.

111. For each efficacy measure, in order for the FEXXOPER therapy to be considered successful, the lower limit of the 95% confidence interval had to be greater than 20%.

112. There is a 95% likelihood that the true success rate for reduction in liver iron concentrate (LIC) falls between 33 and 51%.

113. All of the above. [Correct]

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RESULTS2_C [IF CONDITION=1-5] According to the sales aid, is this statement true or false?

A plot of the hazard ratios summarizing exploratory subgroup analyses suggested treatment benefit for all evaluated subgroups.

114. True [Correct]

115. False

RESULTS2_E [IF CONDITION=6-10] According to the sales aid, is this statement true or false?

Although not statistically significant, patients taking XEDALITI in combination with Rd had a 23% lower risk of death than those taking Rd alone.

116. True [Correct]

117. False

RESULTS2_F [IF CONDITION = 11-15] According the sales aid, is this statement true or false?

Serum ferritin was reduced by more than 20% in 50% of patients treated.

118. True [Correct]

119. False

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RESULTS3_C [IF CONDITION=1-5] According to the sales aid, is this statement true or false?

The benefit of XEDALITI + VULPAFEN was seen whether or not the patient was male or female.

120. True [Correct]

121. False

RESULTS3_E [IF CONDITION=6-10] At the time of the interim analysis, what was the survival probability of patients taking XEDALITI in combination with Rd?

122. 100%

123. 77%

124. 60% [Correct]

125. 53%

126. 23%

RESULTS3_F [IF CONDITION=11-15] What percentage of patients achieved sponsor-defined treatment success for liver iron concentrate (LIC)?

127. 100%

128. 62%

129. 42% [Correct]

130. 50%

131. 20%

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LIMITS_C [IF CONDITION=1-5] Which, if any, of the following limitations are limitations of the analyses presented in the sales aid?

[RANDOMIZE OPTIONS 1-3]

132. The analysis did not appropriately control the false-positive rate in conducting multiple subgroup analyses.

133. There may be an imbalance between the two treatment groups in baseline characteristics.

134. The analysis did not account for the effects of the other subgroup factors.

135. All of the above. [Correct]

136. None of the above.

LIMITS_E [IF CONDITION=6-10] Which, if any, of the following limitations are limitations of the analyses presented in the sales aid?

[RANDOMIZE OPTIONS 1-3]

137. The analyses were conducted before the conclusion of the study. [Correct]

138. The study did not have a control group.

139. There was a high rate of missing data.

140. All of the above.

141. None of the above.
     
     

LIMITS_F [IF CONDITION=11-15] Which, if any, of the following limitations are limitations of the analyses presented in the sales aid?

[RANDOMIZE OPTIONS 1-3]

142. There was a high rate of missing data.

143. The study did not have a control group.

144. There was wide variability of results among the included studies.

145. All of the above. [Correct]

146. None of the above.

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PRELIM Is this statement true or false?

The data presented in the sales aid clearly translates into clinical benefit.

147. True

148. False [Correct]

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[SALES AID LINK NO LONGER AVAILABLE ON SCREEN]

TECHNICAL To what extent do you agree or disagree with the following statement:

Overall, the sales aid used a lot of technical language such as complex terminology, statistical terms, or jargon.

149. Completely disagree

150. Disagree

151. Somewhat disagree

152. Somewhat agree

153. Agree

154. Completely agree

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PREFERENCE Below are two versions of a disclosure statement that could appear in the sales aid for [IF CONDITION=1-10: XEDALITI; IF CONDITION=11-15: FEXXOPER].

[RANDOMIZE ORDER]

Option A. [IF CONDITION=1-5, FILL DRUGX_TECHNICAL, IF CONDITION=6-10, FILL DRUGY_TECHNICAL, IF CONDITION=11-15, FILL DRUGZ_TECHNICAL]

Option B. [IF CONDITION=1-5, FILL DRUGX_NONTECHNICAL, IF CONDITION=6-10, FILL DRUGY_NONTECHNICAL, IF CONDITION=11-15, FILL DRUGZ_NONTECHNICAL]

Which one of the disclosure statements do you prefer?

155. Option A

156. Option B

157. No preference

Conditional text	Display
{DRUGX_TECHNICAL}	In the figure above a Cox model was used to estimate hazard ratios and corresponding 95% confidence intervals for observed treatment effects in various subgroups by baseline characteristics in the study. The subgroup analyses were pre-specified in the statistical analysis plan, but there was no statistical procedure pre-specified in the statistical analysis plan to appropriately control the overall Type 1 error rate at a significance level of two-sided 0.05. The 95% confidence limits shown also do not reflect the effect of a particular factor after adjustment for all other factors. In addition, because the randomization was not stratified by the factor that defines the subgroup, it could cause imbalance between the two treatment groups in baseline characteristics or other known or unknown factors within the subgroup. Therefore, apparent homogeneity or heterogeneity among groups should not be over interpreted.
{DRUGX_NONTECHNICAL}	The figure above presents the observed treatment effects in various subgroups by baseline characteristics in the study. The subgroup results (e.g., disease state, age, sex) are considered exploratory. There was no procedure in place to appropriately control the false positive rate in conducting multiple analyses or to adjust each subgroup analysis to account for the effects of the other subgroup factors. In addition, there may be imbalance in baseline characteristics among the compared subgroups. Therefore, it may not be appropriate to draw conclusions regarding the efficacy of the combination of Xedaliti and Vulpafen for patients with unresectable or metastatic melanoma with BRAF V600E or V600E mutations in these particular subgroups.
{DRUGY_TECHNICAL}	Overall survival (OS) was tested hierarchically after the co-primary endpoints of overall response rate (ORR) and progression free survival (PFS) to preserve the experiment-wise type-I error at the 5% level. No alpha was allocated to OS rate comparisons at specific time points (such as 36 months). The nominal alpha level for OS at interim analysis was calculated using a separate O’Brien Fleming spending function, based on the actual number of deaths observed at the time of analysis (295 deaths). The alpha level for the interim OS analysis (0.014) was calculated as an adjustment to the 295/427 (69%) of data maturity. The p-value of 0.0257 from the interim OS analysis was larger than the threshold of 0.014. Thus, a conclusion that Xedaliti confers a benefit in terms of OS cannot be made at this time.
{DRUGY_NONTECHNICAL}	Overall survival (OS) was a secondary endpoint of this study (progression free survival and overall response rate were the co-primary endpoints). The analysis of overall survival (OS) was conducted before data collection was complete. OS rate comparisons at specific time points (such as 36 months) were exploratory. The p value threshold for the interim OS analysis was adjusted because only 69% of the study had been completed at the time of analysis. The interim analysis was not statistically significant. Thus, a conclusion that Xedaliti confers a benefit in terms of OS cannot be made at this time.
{DRUGZ_TECHNICAL}	These data are derived from an open label, uncontrolled, non-randomized analysis of pre-existing clinical data from 12 studies. The primary endpoint was the change in serum ferritin from baseline within one year of treatment with Fexxoper. Success was calculated as the proportion of patients with a ≥20% decline in serum ferritin from baseline within one year of treatment. Secondary endpoints included change in cardiac MRI T2 and Liver Iron Concentration (LIC) within one year of treatment with Fexxoper. Fexxoper therapy was considered successful in individual patients who experienced a ≥20% increase in cardiac MRI T2* or a ≥20% decline in LIC within one year of therapy. Success rates by study overall and their 95% CIs were calculated based on Clopper-Pearson exact confidence interval. Data were pooled from heterogeneous studies. There were several limitations to these studies; for example, retrospective designs, small sample sizes, lack of control groups, missing data, and missing treatment compliance assessments. There was a high rate of missing data among the pooled studies and significant variations in results among the evaluated studies. These limitations raise an issue of data integrity and heterogeneity that can potentially cause biased results. For serum ferritin, in 33% (4/12) of the studies, the lower bound of the 95% confidence interval was less than the pre-specified target of 20%. For LIC, in 50% (3/6) of the studies, the lower bound of the 95% confidence interval was less than the pre-specified target of 20%. A total of 20 (7.6%), 79 (29.9%), 94 (35.6%) and 127 (48.1%) subjects dropped out of the studies by month 3, 6, 9 and 12, respectively. High dropout rate could make the results unreliable and misleading.
{DRUGZ_NONTECHNICAL}	These data are derived from a retrospective analysis of patients from 12 previous studies. No control group or randomization was used and the drug name was not disguised. The primary endpoint was the change in serum ferritin from baseline within one year of treatment with Fexxoper. Success was calculated as the proportion of patients with a ≥20% decline in serum ferritin from baseline within one year of treatment. Secondary endpoints included change in cardiac MRI T2 and Liver Iron Concentration (LIC) within one year of treatment with Fexxoper. Fexxoper therapy was considered successful in individual patients who experienced a ≥20% increase in cardiac MRI T2* or a ≥20% decline in LIC within one year of therapy. The characteristics (e.g., study design, treatment duration, patient selection criteria, exferperone doses) of the studies from which the patients were selected varied significantly. This pooled analysis has several serious limitations including lack of randomization, lack of control group, high rate of missing data, and ignoring the variation between studies by simple pooling, all of which can potentially cause biased results. For each endpoint, there was a wide variability of success rates among the individual studies that were pooled in the analysis. This was particularly true for serum ferritin and LIC. The number of subjects that dropped out of the studies continued to increase over 12 months. High dropout rates could also make the results unreliable and misleading.

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PREFERWHY [PRETEST ONLY. IF PREFERENCE ≠ 3] Please tell us why you prefer Option [IF PREFERENCE=1: A, IF PREFERENCE=2: B].

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SCRIPT5 FDA designates some new prescription drugs it reviews and approves as “breakthrough drugs” or “breakthrough therapies”.

FAMILIAR How familiar are you with the “breakthrough therapy” designation?

158. Not at all familiar

159. A little familiar

160. Familiar

161. Very familiar

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[IF FAMILIAR = 1, SKIP to BTDV1/BTDV2]

[RANDOMIZE ORDER OF BTKNOW1 AND ACCEL. PRESENT EACH QUESTION ON A SEPARATE SCREEN]

BTKNOW1 For drugs that are intended to treat serious conditions, what is the minimum level of evidence that the FDA requires manufacturers to gather for the FDA to label a drug as a breakthrough?

162. Strong evidence (e.g., randomized trials evaluating clinical outcomes)

163. Preliminary evidence (e.g., uncontrolled studies or studies testing surrogate outcomes) [Correct]

164. Very preliminary evidence (e.g., in vitro lab or animal studies)

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ACCEL Is this statement true or false?

FDA’s breakthrough therapy designation pathway automatically qualifies a drug to receive accelerated approval.

165. True

166. False [Correct]

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[RANDOMIZE WHETHER PARTICIPANT SEES BTDV1 OR BTDV2]

BTDV1 Imagine your patient has a serious medical condition for which there has been no effective treatment. The FDA recently approved 2 new drugs to treat this condition. Both drugs are oral tablets to be taken once a day, have similar adverse effect profiles, and are equally covered by the patient’s insurance.

Which would you choose first?

[RANDOMIZE OPTIONS 1-2]

167. Axabex, an FDA-designated breakthrough drug

168. Zykanta, a drug with early promising study results showing that the drug may demonstrate substantial improvement over available therapies

BTDV2 Imagine your patient has a serious medical condition for which there has been no effective treatment. The FDA recently approved 2 new drugs to treat this condition. Both drugs are oral tablets to be taken once a day, have similar adverse effect profiles, and are equally covered by the patient’s insurance.

Which would you choose first?

[RANDOMIZE OPTIONS 1-2]

169. Zykanta, an FDA-designated breakthrough drug

170. Axabex, a drug with early promising study results showing that the drug may demonstrate substantial improvement over available therapies

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SCRIPT6 We now have just a few more questions about your background and professional experience.

YEARS Since you received your license to treat patients, how many years have you been practicing in your primary specialty?

_______ years [RANGE: 0 to 80]

RX [IF NOT ONCOLOGIST] On average, how many prescriptions for oncology medications do you write each month?

____ prescriptions

SETTING In the past 12 months, in which of the following practice settings have you seen patients for treatment or evaluation? Select all that apply.

[Programmer: Multi-punch response items should be saved to dataset as binary variables with response options: 1=’Selected’ OR 0=’Not selected’.]

SETT1 Academic medical center or medical school

SETT2 Medical center not affiliated with a medical school

SETT3 Community hospital

SETT4 Office-based practice

SETT5 HMO or integrated health care system

SETT6 Other (please specify) ________________

NCI_CENTER Are any of the practice locations where you have seen patients in the past 12 months National Cancer Institute (NCI) cancer centers or NCI cancer center affiliates?

	Yes 1	No 2
NCI_CENTER1 NCI cancer center
NCI_CENTER2 NCI cancer center affiliate

CLINTRIAL In the past 5 years, have you served in any of these roles in a randomized controlled trial (RCT)?

	Yes 1	No 2
CLINTRIAL1 Primary investigator
CLINTRIAL2 Site investigator
CLINTRIAL3 Enrolled patients in an RCT
CLINTRIAL4 Author on a paper reporting findings from an RCT

DRUGREP Do you or your primary practice have any restrictions in place that reduce pharmaceutical sales representatives’ access to you?

171. No restrictions in place

172. Some restrictions (e.g., appointments are required or preferred)

173. Representatives are not granted access

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TRUST In general, how credible do you find prescription drug promotion materials that are marketed to health care providers?

174. Not at all credible

175. Somewhat credible

176. Moderately credible

177. Very credible

178. Completely credible

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[RANDOMIZE ORDER OF POWER AND STATTEST]

POWER How comfortable are you interpreting factors that influence a study’s statistical power?

179. Not at all comfortable

180. Somewhat comfortable

181. Moderately comfortable

182. Very comfortable

183. Extremely comfortable

STATTEST How comfortable are you assessing if the correct statistical tests were used in a study to answer the study’s research question?

184. Not at all comfortable

185. Somewhat comfortable

186. Moderately comfortable

187. Very comfortable

188. Extremely comfortable

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STATLIT I understood all of the statistical terms presented in the sales aid I saw.

189. Completely disagree

190. Disagree

191. Somewhat disagree

192. Somewhat agree

193. Agree

194. Completely agree

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SALESAID In the past 12 months, from which of the following sources have you received sales aids for prescription drugs? Select all that apply.

[RANDOMIZE RESPONSE OPTIONS EXCEPT FOR “NONE” and “OTHER”] [Programmer: Multi-punch response items should be saved to dataset as binary variables with response options: 1=’Selected’ OR 0=’Not selected’.]

SALESAID1          Medical conference or seminar

SALESAID2          Pharmaceutical representative

SALESAID3          Colleague

SALESAID4          Pharmaceutical company webpage

SALESAID5          Medical app (e.g., Epocrates)

SALESAID6          Other (please specify) __________

SALESAID7          None [IF SELECTED, NO OTHER OPTIONS CAN BE SELECTED]

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FDA Was the drug in the sales aid FDA-approved or not FDA-approved?

195. The drug was FDA-approved

196. The drug was not FDA-approved

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DEBRIEF Your responses have been very helpful. Thank you very much for taking part in this survey! The purpose of this study is to learn about how providers feel about scientific data in prescription drug promotions and how they use this information in clinical practice. [IF CONDITION=1-10: XEDALITI; IF CONDITION=11-15: FEXXOPER] is a fictitious drug and is not a product currently for sale.

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