Vaccine package inserts and prescribing habits of obstetricians-gynecologists for maternal vaccination

Figures & data

Table 1. Professional characteristics and practices among a sample of ACOG fellows, N = 321

	Frequency	Percent (%)
Providing care for pregnant women
Yes	280	87.2
No	41	12.8
Medical sub-specialty*
General obstetrics and gynecology	221	68.8
Gynecology only	36	11.2
Maternal fetal medicine	26	8.1
Reproductive endocrinology/infertility	13	4.0
Urogynecology	10	3.1
Obstetrics only	8	2.5
Gynecologic oncology	4	1.2
Other	3	0.9
Years since residency completion
<5 years	20	6.2
5–10 years	50	15.6
11–20 years	101	31.5
21–30 years	89	27.7
30+ years	61	19
Recommend and/or administer vaccines in pregnancy*
Yes	288	90
No	30	9.3
Refuse to answer	2	0.6
Vaccines administered Influenza
Yes	202	62.9
No	119	37.1
TDAP
Yes	191	59.5
No	130	40.5
Both influenza and TDAP	181	56.4
Vaccines prescribed Influenza
Yes	258	80.4
No	63	19.6
TDAP
Yes	235	73.2
No	86	26.8
Both influenza and TDAP	232	72.3
Refuse to answer overall (prescribed and/or administered)	8	2.5

*All columns might not add to 100% due to non-responses or rounding.

Table 2. Vaccine information accessibility and package insert impressions among a sample of ACOG fellows, N = 321

	Frequency	Percent (%)
Commonly used resources for information regarding maternal vaccination*
Professional organizations like ACOG	289	90
CDC’S ACIP recommendations	269	83.8
Articles from high impact factor OB-GYN journals	73	22.7
WHO recommendations	65	20.3
Colleagues	39	12.2
Vaccine package inserts	25	7.8
IDSA guidelines	10	3.1
Refuse to answer	12	3.7
Respondents ever reading package inserts
No	226	70.4
Yes	85	26.5
Refuse to answer	10	3.1
Frequency of reading package inserts*
Rarely	195	60.7
Only if there is a new product/updated insert	56	17.4
Occasionally	46	14.3
Often	10	3.1
Before each administration and/or recommendation	2	0.6
Refuse to answer	11	3.4
Difficulty of wording of package inserts*
Unfamiliar with package inserts	110	34.3
Very hard to read	20	6.2
Hard to read	81	25.2
Neither easy nor hard to read	70	21.8
Easy to read	29	9.0
Very easy to read	4	1.2

*All columns might not add up to 100% due to multiple selections per person, non-responses, or rounding; discrepancies may arise since most participants who responded they do not read package inserts also stated they read them rarely, owing to the lack of a response option for those who wanted to select “never”); CDC: Centers for Disease Control and Prevention, ACIP: Advisory Committee on Immunization Practices, WHO: World Health Organization, IDSA: Infectious Diseases Society of America.

Figure 1. Initial perception of recommending use in pregnant women among ob-gyns in the US: vaccine with Pregnancy Categories labeling vs. vaccine with Pregnancy and Lactation Labeling Rule (N = 321)

Legend: Figure I describes the initial perception of labels and subsequent recommendation with those including Pregnancy Categories labeling versus those following Pregnancy and Lactation Labeling Rule labeling, with responses being “No,” “Yes,” or “No Answer.” PC: Pregnancy Categories, PLLR: Pregnancy and Lactation and Labeling Rule.

Figure 2. Initial perception of safety of use in pregnant women among ob-gyns in the US: Vaccine with Pregnancy Categories labeling vs. vaccine with Pregnancy and Lactation Labeling Rule (N = 321)

Legend: Figure II shows ob-gyns’ initial perception of safety of use in pregnant women with those labels including Pregnancy Categories versus those following Pregnancy and Lactation Labeling Rule, with responses being “Unsafe,” “Safe/Neutral,” or “No Answer.” PC: Pregnancy Categories, PLLR: Pregnancy and Lactation and Labeling Rule.

Table 3. Association of professional characteristics and practices with reading vaccine package inserts among a sample of ACOG fellows, N = 304*

Professional characteristics and practices	Overall*	Read package inserts	Did not read package inserts
	N (%) = 304	n (%) = 82 (27.0)	n (%) = 222 (73.0)
Currently provide care for pregnant women
Yes	275 (90.5)	72 (87.8)	203 (91.4)
No	29 (9.54)	10 (12.2)	19 (8.6)
Medical sub-specialty
General obstetrics and gynecology	219 (72.0)	58 (70.7)	161 (72.5)
Gynecology only	28 (9.2)	12 (14.6)	16 (7.21)
Obstetrics only	8 (2.6)	2 (2.4)	6 (2.7)
Maternal fetal medicine	26 (8.6)	3 (3.7)	23 (10.4)
Other^‡	23 (7.6)	7 (8.5)	16 (7.2)
Years since residency completion^†
<5 years	20 (6.6)	3 (3.7)	17 (7.7)
5–10 years	49 (16.1)	9 (11.0)	40 (18.0)
11–20 years	95 (31.3)	20 (24.4)	75 (33.8)
21–30 years	84 (27.6)	27 (32.9)	57 (25.7)
30+ years	56 (18.4)	23 (28.1)	33 (14.9)
Recommend and/or administer vaccines in pregnancy*^†
Yes	284 (93.4)	72 (87.8)	212 (95.5)
No	20 (6.6)	10 (12.2)	10 (4.5)
Commonly used resources for information regarding maternal vaccination^*§
Professional organizations like ACOG	285 (93.8)	76 (92.7)	209 (94.1)
CDC’S ACIP recommendations	265 (87.2)	70 (85.4)	195 (87.8)
Articles from high impact factor OB-GYN journals	73 (24.0)	19 (23.2)	54 (24.3)
WHO recommendations	65 (21.4)	20 (24.4)	45 (20.3)
Colleagues	39 (12.8)	10 (12.2)	29 (13.1)
Vaccine package inserts^†	25 (8.2)	19 (23.2)	6 (2.7)
IDSA guidelines	10 (3.3)	4 (4.9)	6 (2.7)

*While survey sample was 321, this analysis excludes respondents with a “refuse to answer” or missing response for the outcome “ever read package inserts,” or the categories “commonly read resources for information regarding maternal vaccination,” and “recommend and/or administer vaccines in pregnancy” (total number excluded = 17), column percentages reported; ^† p-value < 0.05 using χ² test or Fisher’s exact test (cell size < 5) of difference in proportions across groups; ^‡ “Other” sub-specialty included reproductive endocrinology/infertility, urogynecology, gynecological oncology, family planning, or obstetrics hospitalist in descending order; ^§Common resources were set-up as binary variables -columns will not add up to 100% due to multiple selections per person; CDC: Centers for Disease Control and Prevention, ACIP: Advisory Committee on Immunization Practices, WHO: World Health Organization, IDSA: Infectious Diseases Society of America.

Figure 3. Overall opinion on and awareness of utility of Pregnancy Categories and Pregnancy and Lactation Labeling Rule among ob-gyns in the US

Legend: Figure III explores the overall opinion and awareness of ob-gyns regarding the utility of labeling with Pregnancy Categories and labeling with Pregnancy and Lactation Labeling Rule, with responses being “I did not know of this labeling,” “I would prefer a combination of both being included in Pregnancy Categories,” “This is less helpful” and “This is more helpful.” PC: Pregnancy Categories, PLLR: Pregnancy and Lactation and Labeling Rule.

Table 4. Themes identified from open-ended question ‘What are your thoughts and comments about package inserts’ safety statements under “pregnancy and lactation” for vaccines that are recommended for use in pregnancy?’.

Themes	Example answers
Does not read/refer to package inserts	‘Would not rely on them for safety. Prefer third party recommendations’ ‘Not familiar enough. as with many products, package inserts are often not consistent with current practices.’ ‘Never look at them’ ‘Does anyone actually read these?’
Manufacturers only care about litigation/package inserts (especially PLLR) are just legal documents	‘Generally no manufacturer will admit that ANYTHING is safe for pregnant women’ ‘These are legal phrases designed to avoid liability’ ‘Too protective for the company and overly state unknown risks’ ‘Written to minimize manufacturers legal exposure not for ease of communication of information or best practice” ‘Long. Ridiculous! CYA bologna!’ ‘Assume that they are “CYA,” and thus don’t pay much attention to them’
Vague/unclear/contradictory	‘Never considered before – just pulled one up for review on the flu vaccine and it states safety and effectiveness not established – this is confusing given the recommendations by CDC and ACOG to administer’ ‘Purposefully vague’ ‘I don’t like that the Tdap insert says “should be given to a pregnant woman only if clearly needed.” Haven’t we established that it is a benefit in pregnancy? Is that the same as “needed”?’ ‘Should be simplified and based on scientific data, not manufacturer guides and precautions’ ‘It is not any different from a category B statement. I have never enrolled my pregnant patients in XXXX’s registry’
Package inserts are for patients	‘Should be clear enough for patient to understand’ ‘Not clear to the average provider and patient’ ‘Would be helpful to have more detailed/easy to read inserts for patients re: vaccines’ ‘Difficult for patients to understand’
Positive comments about PLLR	‘The overall inserts are long and difficult but the pregnancy and lactation sections are not alarming’ ‘Important – should always be thoroughly stated’ ‘Very helpful + aids in discussion with patient’ ‘Very much needed’
Prefer ACOG/CDC recommendations	‘Often a clumped recommendation – I don’t generally trust this over ACOG/CDC’ ‘I usually don’t look at them. Use ACOG+CDC guidelines’ ‘I have never read them, would use guidelines to make recommendations. Similar to drug package inserts; I also don’t read those’ ‘I go with ACOG recommendations – > if they advise it, it doesn’t matter what package insert says’
Table 4. Themes identified from open-ended question ‘do you have any other comments on vaccine package inserts and maternal immunization to add?’
Themes	Example answers
Too complex/prefer CDC or ACOG guidelines	‘State recommendations by ACOG/CDC, include any trimester exclusion, include disease risk reduction by giving vaccine, # of adverse outcomes in registry’ ‘Clinically the recommendations of societies, i.e. CDC, ACOG, IDSA, SMFM are incredibly helpful. Difficult to find all primary data and interpret as busy clinician. Reliance on “experts” to review and recommend is much more important than package insert. If no recommendation yet then more information rather than less better in package inserts’ ‘As a practicing physician, we just want to know if the medication is safe for pregnancy or lactation. Most of the wording, in my opinion, is CYA for the manufacturer. It leaves us deciding whether or not it should be used. Fortunately, the CDC and ACOG do help.’ ‘Need to be more clear’
Surveillance registry	‘If ACOG (or) CDC makes it mandatory to register pregnant women in the vaccine registry, we might be able to collect the data for the future/for our pregnant patients’ ‘I think a national vaccine database website cosponsored by the CDC/ACOG/WHO with an easy to use mobile app would be the most helpful, user friendly approach for busy provider’
Comfortable with old rules	‘Hard to erase 20 years of using old ways:)’ ‘I grew up with old rules. was comfortable with them – best would be combination for older MDs – the new MDs get trained in new rules – I find new rules unclear’
Push for patient centered inserts	‘We need patient driven materials, materials that are written in basic language that describes exactly what the vaccine is and how it helps. We need CDC/ACOG and organizations to increase education of vaccines in schools and media’ ‘For very health literate patients, the PLLR might be helpful’ ‘Many of our patients are misinformed by non-medical sources against the safety of vaccines such as social media, google, friends etc. – hard to overcome’ ‘Too extensive and confusing for patients’
Advice for changes to labeling	‘Pregnancy Categories are easier and faster but more data can be helpful to understand exactly what we know. That’s why I’d like both!’ ‘The risks of not vaccinated should be clearly stated’ ‘“clearly needed” is just terrible language. This is way too open for interpretation for something that is designed to prevent a problem’ ‘Have inserts list results and titles of studies’ ‘Larger print outside boxed warnings would be helpful!’
Do not read inserts	‘Doing this survey tells me I have relied too much on what the governing bodies say since I don’t look at package inserts’ ‘Amazing how much I do not know. I will make sure to go read those inserts!’ ‘Perhaps I should read them more’ ‘I don’t know anyone who reads the package insert – other than for administration or maybe storage temp for a vaccine! refer to CDC/College guidelines!’
Manufacturers only care about litigation/package inserts are just legal documents	‘Lots of disclaimers, no commitment’ ‘I follow ACOG + CDC guidelines and haven’t been reading immunization package inserts b/c of those recommendations, but I can see how the inserts can be more ‘CYA’ than helpful … ’ ‘Often FDA package inserts frighten patients and do not improve patient care.’ ‘Not truthful’ ‘I do not rely on packing inserts. It is my assumption that this information is more about avoidance of litigation than best medical evidence. The CDC is my primary resource for evaluation of the best clinical evidence and review of risk/benefit for vaccines in pregnancy’