Supplementary Information

Supplementary Text

Northeast: Connecticut; Delaware; District of Columbia; Maine; Maryland; Massachusetts; New Hampshire; New Jersey; New York; Pennsylvania; Rhode Island; Vermont
North Central: Illinois; Indiana; Iowa; Kansas; Kentucky; Michigan; Minnesota; Missouri; Nebraska; North Dakota; Ohio; South Dakota; Wisconsin
South: Alabama; Arkansas; Florida; Georgia; Louisiana; Mississippi; North Carolina; Oklahoma; South Carolina; Tennessee; Texas; Virginia; West Virginia
West: California; Oregon; Washington; Idaho; Montana; Nevada; Utah; Colorado; Wyoming; Arizona; New Mexico; Alaska, Hawaii

Supplementary Figure 1

Patient adherence to blood Phe testing frequency recommended by their clinic

Note: figure excludes patients for whom adherence to testing frequency recommendations was unknown: 4% of children and 7-9% of adults.


Supplementary Table 1

Correlations between the proportion of patients non-adherent to clinic recommendations regarding blood Phe concentrations and the proportion of patients non-adherent to clinic recommendations on blood testing frequency for a given clinic and age group

Proportion of patients non-adherent to clinic blood testing frequency recommendations
Age 0-1 / Age 1-4 / Age 5-12 / Age 13-17 / Age 18-29 / Age 30+ / Pregnant/ planning to become pregnant
Proportion of patients 0-4 that are above the clinic Phe target / Pearson Correlation / 0.058 / 0.083 / -0.143 / -0.071 / -0.118 / -0.358 / 0.304
Sig. (2-tailed) / 0.744 / 0.620 / 0.392 / 0.676 / 0.487 / 0.038 / 0.131
N / 34 / 38 / 38 / 37 / 37 / 34 / 26
Proportion of patients 5-12 that are above the clinic Phe target / Pearson Correlation / -0.168 / 0.107 / -0.203 / 0.211 / 0.093 / -0.042 / 0.218
Sig. (2-tailed) / 0.343 / 0.523 / 0.222 / 0.210 / 0.585 / 0.812 / 0.284
N / 34 / 38 / 38 / 37 / 37 / 34 / 26
Proportion of patients 13-17 that are above the clinic Phe target / Pearson Correlation / -0.247 / 0.109 / 0.112 / 0.121 / 0.086 / -0.115 / -0.148
Sig. (2-tailed) / 0.159 / 0.521 / 0.511 / 0.475 / 0.617 / 0.525 / 0.471
N / 34 / 37 / 37 / 37 / 36 / 33 / 26
Proportion of patients 18-29 that are above the clinic Phe target / Pearson Correlation / 0.032 / 0.326 / 0.116 / 0.461 / 0.294 / 0.192 / 0.113
Sig. (2-tailed) / 0.859 / 0.049 / 0.495 / 0.005 / 0.078 / 0.277 / 0.583
N / 33 / 37 / 37 / 36 / 37 / 34 / 26
Proportion of patients 30+ that are above the clinic Phe target / Pearson Correlation / -0.115 / -0.010 / -0.263 / 0.171 / 0.127 / 0.118 / -0.171
Sig. (2-tailed) / 0.538 / 0.956 / 0.133 / 0.341 / 0.473 / 0.513 / 0.402
N / 31 / 34 / 34 / 33 / 34 / 33 / 26
Proportion of pregnant/planning patients that are above the clinic Phe target / Pearson Correlation / 0.120 / -0.064 / -0.018 / -0.009 / 0.243 / 0.071 / 0.393
Sig. (2-tailed) / 0.526 / 0.732 / 0.922 / 0.963 / 0.195 / 0.715 / 0.047
N / 30 / 31 / 31 / 31 / 30 / 29 / 26

Relevant correlations are highlighted in light yellow, significant (p<0.05) correlation is highlighted in orange and bolded.

Supplementary Table 2

Correlations between the proportion of patients non-adherent to clinic recommendations regarding blood Phe concentrations and the estimated actual blood testing frequency for a given clinic and age group.

Weighted frequency of blood testing
Age 0-1 / Age 1-4 / Age 5-12 / Age 13-17 / Age 18-29 / Age 30+ / Pregnant/ planning to become pregnant
Proportion of patients 0-4 that are above the clinic Phe target / Pearson Correlation / -0.023 / 0.046 / 0.096 / 0.042 / 0.047 / 0.191 / -0.288
Sig. (2-tailed) / 0.890 / 0.771 / 0.540 / 0.795 / 0.769 / 0.245 / 0.110
N / 39 / 43 / 43 / 41 / 41 / 39 / 32
Proportion of patients 5-12 that are above the clinic Phe target / Pearson Correlation / 0.203 / 0.074 / 0.139 / 0.009 / 0.074 / 0.155 / -0.350
Sig. (2-tailed) / 0.215 / 0.639 / 0.373 / 0.956 / 0.644 / 0.346 / 0.049
N / 39 / 43 / 43 / 41 / 41 / 39 / 32
Proportion of patients 13-17 that are above the clinic Phe target / Pearson Correlation / 0.268 / 0.157 / 0.058 / -0.103 / 0.037 / 0.096 / 0.054
Sig. (2-tailed) / 0.104 / 0.326 / 0.720 / 0.521 / 0.820 / 0.570 / 0.769
N / 38 / 41 / 41 / 41 / 40 / 37 / 32
Proportion of patients 18-29 that are above the clinic Phe target / Pearson Correlation / 0.141 / -0.037 / -0.019 / -0.123 / -0.066 / -0.017 / 0.044
Sig. (2-tailed) / 0.407 / 0.817 / 0.906 / 0.450 / 0.682 / 0.918 / 0.810
N / 37 / 41 / 41 / 40 / 41 / 38 / 32
Proportion of patients 30+ that are above the clinic Phe target / Pearson Correlation / 0.051 / -0.046 / 0.217 / -0.010 / 0.018 / 0.016 / 0.033
Sig. (2-tailed) / 0.770 / 0.785 / 0.190 / 0.952 / 0.915 / 0.926 / 0.857
N / 35 / 38 / 38 / 36 / 37 / 38 / 32
Proportion of pregnant/planning patients that are above the clinic Phe target / Pearson Correlation / -0.115 / 0.024 / -0.004 / -0.052 / -0.204 / -0.115 / -0.531
Sig. (2-tailed) / 0.525 / 0.894 / 0.984 / 0.772 / 0.254 / 0.523 / 0.002
N / 33 / 34 / 34 / 34 / 33 / 33 / 32

Note: Weighted average blood testing frequency for a given clinic within a given age group is calculated by taking the proportion of patients testing with a given frequency (e.g., monthly) multiplied by the corresponding frequency in times/year (i.e. 12).

Relevant correlations are highlighted in light yellow, significant (p<0.05) correlation is highlighted in orange and bolded.

Supplementary Figure 2

Frequency of PKU clinic visits (excluding contacts outside of clinics such as phone calls)

Note: figure excludes patients for whom clinic visit frequency was unknown: 3-4% of children and 6-8% of adults.

Supplementary Table 3

Correlations between the number of full-time PKU specialists per 100 actively managed PKU patients and the annual frequency of clinic visits

Patients non-adherent to clinic blood Phe recommendations
Age 0-1
(N=39) / Age 0-4
(N=43) / Age 5-12
(N=43) / Age 13-17
(N=41) / Age 18-29
(N=41) / Age 30+
(N=39) / Pregnant/ planning to become pregnant
(N=31)
Total number of HCPs per 100 patients / r / -0.217 / -0.190 / -0.182 / 0.034 / -0.076 / -0.125 / 0.012
P-value / 0.184 / 0.222 / 0.242 / 0.833 / 0.635 / 0.449 / 0.947
Number of full-time physicians per 100 patients / r / -0.140 / -0.214 / -0.200 / -0.106 / -0.136 / -0.156 / -0.037
P-value / 0.397 / 0.168 / 0.199 / 0.509 / 0.395 / 0.342 / 0.844
Number of full-time dietitians per 100 patients / r / -0.147 / -0.253 / -0.281 / -0.074 / -0.213 / -0.213 / -0.190
P-value / 0.372 / 0.101 / 0.068 / 0.647 / 0.180 / 0.192 / 0.307
Number of full-time social workers per 100 patients / r / -0.201 / -0.202 / -0.163 / -0.131 / -0.053 / -0.115 / 0.057
P-value / 0.220 / 0.194 / 0.297 / 0.415 / 0.741 / 0.486 / 0.760
Number of full-time psychologists / neuropsychologists per 100 patients / r / -0.160 / -0.013 / 0.033 / 0.016 / 0.081 / 0.084 / 0.268
P-value / 0.330 / 0.935 / 0.832 / 0.920 / 0.614 / 0.609 / 0.144
Number of full-time nurse practitioners per 100 patients / r / -0.254 / -0.086 / -0.101 / -0.151 / -0.055 / -0.112 / -0.103
P-value / 0.118 / 0.586 / 0.521 / 0.347 / 0.732 / 0.496 / 0.581
Number of full-time genetic counselors per 100 patients / r / -0.114 / -0.004 / -0.018 / 0.333 / 0.045 / 0.022 / 0.165
P-value / 0.490 / 0.981 / 0.907 / 0.034 / 0.780 / 0.893 / 0.376

Relevant P-values are highlighted in light yellow, significant (p<0.05) correlations are highlighted in orange and bolded. No correction for multiple comparisons was made.

r – Pearson correlation coefficient

PKU Questionnaire

SCREENER

S1.  Which of the following best describes your primary specialty?

a.  Orthopedics/Orthopedic Surgery [DISQUALIFY]

b.  Internal Medicine

c.  Family Practitioner

d.  General Practitioner

e.  Dietitian

f.  Endocrinologist

g.  Pediatrician

h.  Geneticist

i.  Metabolic Specialist

j.  Psychologist / neuropsychologist

k.  Registered Nurse

l.  Nurse Practitioner

m.  Other (Please specify ______) [DISQUALIFY]

S2.  Do you specialize in the treatment of patients with phenylketonuria (PKU)?

a.  Yes

b.  No [DISQUALIFY]

S3.  In which region of the country is your clinic located where you treat PKU patients?

A.  Northeast:
Connecticut; Delaware; District of Columbia; Maine; Maryland; Massachusetts; New Hampshire; New Jersey; New York; Pennsylvania; Rhode Island; Vermont / q 1
B.  North Central:
C.  Illinois; Indiana; Iowa; Kansas; Kentucky; Michigan; Minnesota; Missouri; Nebraska; North Dakota; Ohio; South Dakota; Wisconsin / q 2
D.  South:
E.  Alabama; Arkansas; Florida; Georgia; Louisiana; Mississippi; North Carolina; Oklahoma; South Carolina; Tennessee; Texas; Virginia; West Virginia / q 3
West:
California; Oregon; Washington; Idaho; Montana; Nevada; Utah; Colorado; Wyoming; Arizona; New Mexico; Alaska, Hawaii / q 4

S4.  How many patients diagnosed with PKU does your clinic actively manage (that is, patients that have been seen in clinic within the past 3 years)?

______

[DISQUALIFY IF S4 < 15]

S5.  Of the [INSERT S4] patients diagnosed with PKU that your clinic is actively managing in total, how many fall into each of the following age groups? Please try to be as precise as possible.

a.  ___ patients 0 to 4 years of age

b.  ___ patients 5 to 12 years of age

c.  ___ patients 13 to 17 years of age

d.  ___ patients 18 to 29 years of age

e.  ___ patients >= 30 years of age

S6.  How many of the [INSERT S4] patients that your clinic is actively managing are currently pregnant or planning on becoming pregnant soon (i.e., within the next 12 months)?

a.  ___ patients that are pregnant or planning on becoming pregnant soon (i.e., within the next 12 months)

Note: for the remaining sections respondents were strongly encouraged to leverage their patient database to appropriately and accurately respond to all relevant survey questions. If respondents were unable to report accurately on all the PKU patients in their clinic, they were asked to select a random subset of patients representative of about 1/3 of their practice for whom they could precisely report the results using patient listings and chart review as needed. Respondents were asked to try to be as precise as possible and involve all members of their PKU Clinic Team to assist with responding to the survey questions.

Clinic Background

1. For how many years has your clinic been managing PKU patients?

a.  ____ years

2. Which best describes your primary practice setting? Please select one.

a.  Academic specialty/multi-specialty office

b.  Academic/hospital practice

c.  Non-academic hospital practice

d.  Non-academic specialty/multi-specialty office

e.  Other (Please specify ______)

3. How many of each of the following specialties that treat PKU patients work full-time within your clinic? Please exclude those available by referral or consult only.

a.  ____ number of full-time physicians

b.  ____ number of full-time dietitians

c.  ____ number of full-time social workers

d.  ____ number of full-time psychologists / neuropsychologists

e.  ____ number of full-time nurse practitioners

f.  ____ number of full-time genetic counselors

4. Earlier you mentioned that your clinic is actively managing [INSERT S4] PKU patients (that is, patients that have been seen within the past 3 years). How many patients diagnosed with PKU does your clinic follow in total, including those you indicated are actively followed (seen within the past 3 years) and those inactively followed (not seen within the past 3 years)? Please try to be as precise as possible.

______PKU patients followed in total

5. Of the [INSERT Q4] patients diagnosed with PKU that are followed by your clinic in total, how many fall into each of the following age groups? Please try to be as precise as possible.

a.  ___ patients 0 to 4 years of age

b.  ___ patients 5 to 12 years of age

c.  ___ patients 13 to 17 years of age

d.  ___ patients 18 to 29 years of age

e.  ___ patients >= 30 years of age

6. Of the [INSERT Q4] patients diagnosed with PKU that are followed by your clinic in total, how many are currently pregnant or planning on becoming pregnant soon (i.e., within the next 12 months)?

a.  ___ patients that are pregnant or planning on becoming pregnant within the next 12 months

Clinic Protocols

For the remainder of the survey, we will be focusing on the PKU patients that your clinic actively manages (that is, patients that have been seen in clinic within the past 3 years).

7. What is your clinic’s current recommended target blood Phe “goal” for PKU patients in each of the following patient groups? Please enter the lower and upper limits of the recommended target range for each group. If there are no distinctions in protocols by group, please indicate the same answers for all 6 groups.