代码
library(ivdtools)
library(readr)8 稀释回收与HOOK
本文演示如何使用 ivdtools 包分析稀释回收、加标回收和高剂量钩状效应。稀释回收用于评价稀释后结果能否按稀释倍数还原，加标回收用于评价加入分析物后的实测增量，高剂量钩状效应用于识别高浓度样本信号下降并重新进入测量区间的风险。
三个分析路径都涉及浓度或响应的变化，但输入数据、分母和结论不同：
| 分析路径 | 主要输入 | 主要返回结果 |
|---|---|---|
| 稀释回收 | 原样编号、测量结果、稀释倍数及可选赋值 | 靶值、稀释校正浓度、单样本回收率及跨样本区间 |
| 加标回收 | 分析物加标与等体积溶剂对照结果、理论加入浓度 | 观测增量、单样本及跨样本回收率 |
| 高剂量钩状效应 | 已知浓度、原始响应、ULoQ 及可选试验序列 | 浓度水平汇总、钩状效应界限和未观察到钩状效应时的下限 |
重要使用边界
本章函数只进行数据汇总、回收率计算、区间估计和钩状效应界限识别，不内置接受标准，也不自动建立或验证扩展测量区间（EMI）。稀释液、稀释倍数、加标材料、样本类型、ULoQ、最高试验浓度和允许回收范围必须在查看结果前确定。
8.1 主要函数
| 函数 | 用途 | 返回值 |
|---|---|---|
dilution_recovery() |
计算稀释靶值、校正浓度和回收率 | dilution_recovery 对象 |
spike_concentration() |
按质量平衡计算加标后的理论浓度 | spike_concentration 数据框 |
spike_recovery() |
计算分析物加标相对溶剂对照的回收率 | spike_recovery 对象 |
hook_effect() |
汇总高浓度响应并识别钩状效应界限 | hook_effect 对象 |
8.1.1 稀释回收 dilution_recovery()
调用形式
代码
dilution_recovery(
data,
sample,
result,
dilution_factor,
assigned = NULL,
diluent_value = 0,
conf.level = 0.95
)
plot(x, type = c("recovery", "summary", "observed"))参数
| 参数 | 说明 |
|---|---|
data |
长格式数据框，每行是一项测量结果。 |
sample |
原样编号列的列名。 |
result |
数值型测量结果列的列名。 |
dilution_factor |
数值型稀释倍数列的列名；未稀释为 1，1/2 稀释为 2。 |
assigned |
可选的原样赋值列；省略时以每份样本未稀释结果的均值作为原样浓度。 |
diluent_value |
稀释液中的分析物浓度，默认为 0。 |
conf.level |
同一稀释倍数跨样本平均回收率的置信水平。 |
返回值
返回 dilution_recovery 类对象。results 保存各“样本 × 稀释倍数”的重复数、均值、SD、CV、原样赋值、靶值、稀释校正浓度和回收率；summary 保存各稀释倍数的样本数、平均回收率、SD、SE、自由度和置信区间；data 与 excluded 分别保存进入分析的数据和被排除的原始行号。plot() 的 type 可选择单样本回收率、跨样本汇总或实测结果图。
8.1.2 加标浓度 spike_concentration()
调用形式
代码
spike_concentration(
sample_concentration,
sample_volume,
stock_concentration,
spike_volume
)参数
| 参数 | 说明 |
|---|---|
sample_concentration |
加标前样本浓度。 |
sample_volume |
参加混合的样本体积。 |
stock_concentration |
加标材料浓度。 |
spike_volume |
加入的加标材料体积。 |
四个参数均接受有限数值向量，并按 R 的普通向量循环规则配对；浓度单位和体积单位必须分别保持一致。
返回值
返回 spike_concentration 类数据框，包含输入浓度和体积、total_volume、spike_fraction、 added_concentration 以及混合后的 final_concentration。
8.1.3 加标回收 spike_recovery()
调用形式
代码
spike_recovery(
data,
sample,
result,
condition,
analyte_level,
solvent_level,
added_concentration = NULL,
sample_volume = NULL,
stock_concentration = NULL,
spike_volume = NULL,
conf.level = 0.95
)
plot(x)参数
| 参数 | 说明 |
|---|---|
data |
长格式加标试验数据框。 |
sample |
样本编号列的列名。 |
result |
数值型测量结果列的列名。 |
condition |
区分分析物加标与溶剂对照的条件列。 |
analyte_level、solvent_level |
分别标识分析物加标和溶剂对照条件的取值。 |
added_concentration |
最终混合液中的理论加入浓度，可为单个数值或数据列；提供后不再由体积计算。 |
sample_volume、 stock_concentration、 spike_volume |
未提供 added_concentration 时用于计算理论加入浓度，可为单个数值或数据列。 |
conf.level |
跨样本平均回收率的置信水平。 |
返回值
返回 spike_recovery 类对象。results 保存每份样本两个条件的重复数、均值和 SD，以及观测增量、理论加入浓度和回收率；summary 保存跨样本平均回收率、SD、SE、自由度和置信区间；data 与 excluded 保存分析数据和被排除行号；plot() 返回各样本回收率图。
8.1.4 高剂量钩状效应 hook_effect()
调用形式
代码
hook_effect(
data,
concentration,
response,
series = NULL,
uloq,
uloq_response = NULL,
conf.level = 0.95
)
plot(x)参数
| 参数 | 说明 |
|---|---|
data |
含已知浓度和原始响应的数据框。 |
concentration |
数值型已知浓度列的列名。 |
response |
数值型原始响应列的列名，不能使用仪器截断后的报告浓度替代。 |
series |
可选的独立钩状效应试验序列列。 |
uloq |
分析测量区间上限浓度。 |
uloq_response |
可选的 ULoQ 原始响应；省略时每个序列必须包含 concentration == uloq 的记录。 |
conf.level |
各浓度平均原始响应的置信水平。 |
返回值
返回 hook_effect 类对象。level_summary 保存各“序列 × 浓度”的重复数、均值、SD、CV、SE 和置信区间；results 保存 ULoQ 响应、钩状效应界限、首次回落至 ULoQ 响应范围内的浓度以及最高试验浓度；minimum_hook_concentration 为所有序列中最保守的界限；data 与 excluded 保存分析数据和被排除行号。函数不在相邻浓度之间插值。
8.2 分析案例
8.2.1 CLSI EP34 表 1：单样本稀释液适用性
EP34 表 1 对同一份原样和 1/2、1/4、1/10、1/20 四级稀释样本各测量 3 次。未提供独立赋值，因此 dilution_recovery() 以未稀释结果的均值作为原样浓度。
代码
ep34_table1 <- read_csv(
"./data/008-稀释回收与HOOK/std-ep34-table1-single-sample.csv",
show_col_types = FALSE
)
head(ep34_table1, 6)# A tibble: 6 × 6
sample dilution fraction replicate observed dilution_factor
<chr> <chr> <dbl> <dbl> <dbl> <dbl>
1 EP34-Table1 neat 1 1 624. 1
2 EP34-Table1 1/2 0.5 1 293. 2
3 EP34-Table1 1/4 0.25 1 156. 4
4 EP34-Table1 1/10 0.1 1 63.1 10
5 EP34-Table1 1/20 0.05 1 34.1 20
6 EP34-Table1 neat 1 2 629. 1代码
ep34_table1_result <- dilution_recovery(
ep34_table1,
sample = "sample",
result = "observed",
dilution_factor = "dilution_factor",
conf.level = 0.95
)
ep34_table1_result
Dilution recovery
Samples: 1
Dilution factors: 1, 2, 4, 10, 20
Confidence level: 95.0%
Dilution factor: 1
Specimen content : 100
Samples : 1
Mean recovery : 100
SD recovery : NA
SE recovery : NA
Degrees of freedom : NA
CI lower : NA
CI upper : NA
Dilution factor: 2
Specimen content : 50
Samples : 1
Mean recovery : 95.583142
SD recovery : NA
SE recovery : NA
Degrees of freedom : NA
CI lower : NA
CI upper : NA
Dilution factor: 4
Specimen content : 25
Samples : 1
Mean recovery : 101.46518
SD recovery : NA
SE recovery : NA
Degrees of freedom : NA
CI lower : NA
CI upper : NA
Dilution factor: 10
Specimen content : 10
Samples : 1
Mean recovery : 105.81278
SD recovery : NA
SE recovery : NA
Degrees of freedom : NA
CI lower : NA
CI upper : NA
Dilution factor: 20
Specimen content : 5
Samples : 1
Mean recovery : 99.312696
SD recovery : NA
SE recovery : NA
Degrees of freedom : NA
CI lower : NA
CI upper : NA
Sample results
Sample: EP34-Table1 | Dilution factor: 1
Replicates : 3
Mean result : 625.63333
SD result : 3.1214313
CV result : 0.49892343
Specimen content : 100
Assigned value : 625.63333
Target concentration : 625.63333
Corrected concentration : 625.63333
Recovery : 100
Sample: EP34-Table1 | Dilution factor: 2
Replicates : 3
Mean result : 299
SD result : 6.2793312
CV result : 2.1001108
Specimen content : 50
Assigned value : 625.63333
Target concentration : 312.81667
Corrected concentration : 598
Recovery : 95.583142
Sample: EP34-Table1 | Dilution factor: 4
Replicates : 3
Mean result : 158.7
SD result : 2.8213472
CV result : 1.7777865
Specimen content : 25
Assigned value : 625.63333
Target concentration : 156.40833
Corrected concentration : 634.8
Recovery : 101.46518
Sample: EP34-Table1 | Dilution factor: 10
Replicates : 3
Mean result : 66.2
SD result : 3.6345564
CV result : 5.4902664
Specimen content : 10
Assigned value : 625.63333
Target concentration : 62.563333
Corrected concentration : 662
Recovery : 105.81278
Sample: EP34-Table1 | Dilution factor: 20
Replicates : 3
Mean result : 31.066667
SD result : 2.7934447
CV result : 8.9917748
Specimen content : 5
Assigned value : 625.63333
Target concentration : 31.281667
Corrected concentration : 621.33333
Recovery : 99.312696打印汇总结果中的 SD、SE 和置信区间是根据“同一稀释倍数下不同样本的回收率”计算的，而不是根据3次重复测量计算的。所以这些值均为 NA。
代码
plot(ep34_table1_result, type = "recovery")
| 标准位置 | 统计量 | 标准结果 | ivdtools结果 |
|---|---|---|---|
| neat | recovery | 100.00 | 100.000 |
| 1/2 | recovery | 95.59 | 95.583 |
| 1/4 | recovery | 101.47 | 101.465 |
| 1/10 | recovery | 105.75 | 105.813 |
| 1/20 | recovery | 99.36 | 99.313 |
软件直接使用未舍入的三次均值，标准表则先把观测均值和靶值显示到一位小数后计算，因此回收率相差不超过 0.07 个百分点。按原文示例预设的 90%～110% 范围，五个稀释水平的点估计均在限内；该范围不是函数内置标准。
8.2.2 CLSI EP34 表 2：多原样本稀释
表 2 给出 5 份原样在相同五级稀释下的观测均值。原文没有公布这些均值背后的全部重复结果，因此输入数据保持汇总粒度，每个“样本 × 稀释水平”一行。
代码
ep34_table2 <- read_csv(
"./data/008-稀释回收与HOOK/std-ep34-table2-multiple-samples.csv",
show_col_types = FALSE
)
head(ep34_table2, 6)# A tibble: 6 × 6
sample dilution fraction observed_mean assigned dilution_factor
<dbl> <chr> <dbl> <dbl> <dbl> <dbl>
1 1 neat 1 506 506 1
2 1 1/2 0.5 264. 506 2
3 1 1/4 0.25 120. 506 4
4 1 1/10 0.1 46 506 10
5 1 1/20 0.05 27.2 506 20
6 2 neat 1 598 598 1代码
ep34_table2_result <- dilution_recovery(
ep34_table2,
sample = "sample",
result = "observed_mean",
dilution_factor = "dilution_factor",
assigned = "assigned",
conf.level = 0.95
)
ep34_table2_result
Dilution recovery
Samples: 5
Dilution factors: 1, 2, 4, 10, 20
Confidence level: 95.0%
Dilution factor: 1
Specimen content : 100
Samples : 5
Mean recovery : 100
SD recovery : 0
SE recovery : 0
Degrees of freedom : 4
CI lower : 100
CI upper : 100
Dilution factor: 2
Specimen content : 50
Samples : 5
Mean recovery : 100.53079
SD recovery : 3.5222063
SE recovery : 1.5751786
Degrees of freedom : 4
CI lower : 96.157389
CI upper : 104.90418
Dilution factor: 4
Specimen content : 25
Samples : 5
Mean recovery : 102.74826
SD recovery : 5.3015808
SE recovery : 2.370939
Degrees of freedom : 4
CI lower : 96.165478
CI upper : 109.33104
Dilution factor: 10
Specimen content : 10
Samples : 5
Mean recovery : 101.81449
SD recovery : 8.2466472
SE recovery : 3.6880127
Degrees of freedom : 4
CI lower : 91.574928
CI upper : 112.05406
Dilution factor: 20
Specimen content : 5
Samples : 5
Mean recovery : 99.785763
SD recovery : 8.8098638
SE recovery : 3.9398909
Degrees of freedom : 4
CI lower : 88.846872
CI upper : 110.72465
Sample results
Sample: 1 | Dilution factor: 1
Replicates : 1
Mean result : 506
SD result : NA
CV result : NA
Specimen content : 100
Assigned value : 506
Target concentration : 506
Corrected concentration : 506
Recovery : 100
Sample: 2 | Dilution factor: 1
Replicates : 1
Mean result : 598
SD result : NA
CV result : NA
Specimen content : 100
Assigned value : 598
Target concentration : 598
Corrected concentration : 598
Recovery : 100
Sample: 3 | Dilution factor: 1
Replicates : 1
Mean result : 570.4
SD result : NA
CV result : NA
Specimen content : 100
Assigned value : 570.4
Target concentration : 570.4
Corrected concentration : 570.4
Recovery : 100
Sample: 4 | Dilution factor: 1
Replicates : 1
Mean result : 625.6
SD result : NA
CV result : NA
Specimen content : 100
Assigned value : 625.6
Target concentration : 625.6
Corrected concentration : 625.6
Recovery : 100
Sample: 5 | Dilution factor: 1
Replicates : 1
Mean result : 561.2
SD result : NA
CV result : NA
Specimen content : 100
Assigned value : 561.2
Target concentration : 561.2
Corrected concentration : 561.2
Recovery : 100
Sample: 1 | Dilution factor: 2
Replicates : 1
Mean result : 264.5
SD result : NA
CV result : NA
Specimen content : 50
Assigned value : 506
Target concentration : 253
Corrected concentration : 529
Recovery : 104.54545
Sample: 2 | Dilution factor: 2
Replicates : 1
Mean result : 294.4
SD result : NA
CV result : NA
Specimen content : 50
Assigned value : 598
Target concentration : 299
Corrected concentration : 588.8
Recovery : 98.461538
Sample: 3 | Dilution factor: 2
Replicates : 1
Mean result : 292.1
SD result : NA
CV result : NA
Specimen content : 50
Assigned value : 570.4
Target concentration : 285.2
Corrected concentration : 584.2
Recovery : 102.41935
Sample: 4 | Dilution factor: 2
Replicates : 1
Mean result : 299
SD result : NA
CV result : NA
Specimen content : 50
Assigned value : 625.6
Target concentration : 312.8
Corrected concentration : 598
Recovery : 95.588235
Sample: 5 | Dilution factor: 2
Replicates : 1
Mean result : 285.2
SD result : NA
CV result : NA
Specimen content : 50
Assigned value : 561.2
Target concentration : 280.6
Corrected concentration : 570.4
Recovery : 101.63934
Sample: 1 | Dilution factor: 4
Replicates : 1
Mean result : 119.6
SD result : NA
CV result : NA
Specimen content : 25
Assigned value : 506
Target concentration : 126.5
Corrected concentration : 478.4
Recovery : 94.545455
Sample: 2 | Dilution factor: 4
Replicates : 1
Mean result : 154.1
SD result : NA
CV result : NA
Specimen content : 25
Assigned value : 598
Target concentration : 149.5
Corrected concentration : 616.4
Recovery : 103.07692
Sample: 3 | Dilution factor: 4
Replicates : 1
Mean result : 151.8
SD result : NA
CV result : NA
Specimen content : 25
Assigned value : 570.4
Target concentration : 142.6
Corrected concentration : 607.2
Recovery : 106.45161
Sample: 4 | Dilution factor: 4
Replicates : 1
Mean result : 158.7
SD result : NA
CV result : NA
Specimen content : 25
Assigned value : 625.6
Target concentration : 156.4
Corrected concentration : 634.8
Recovery : 101.47059
Sample: 5 | Dilution factor: 4
Replicates : 1
Mean result : 151.8
SD result : NA
CV result : NA
Specimen content : 25
Assigned value : 561.2
Target concentration : 140.3
Corrected concentration : 607.2
Recovery : 108.19672
Sample: 1 | Dilution factor: 10
Replicates : 1
Mean result : 46
SD result : NA
CV result : NA
Specimen content : 10
Assigned value : 506
Target concentration : 50.6
Corrected concentration : 460
Recovery : 90.909091
Sample: 2 | Dilution factor: 10
Replicates : 1
Mean result : 65.3
SD result : NA
CV result : NA
Specimen content : 10
Assigned value : 598
Target concentration : 59.8
Corrected concentration : 653
Recovery : 109.19732
Sample: 3 | Dilution factor: 10
Replicates : 1
Mean result : 61.6
SD result : NA
CV result : NA
Specimen content : 10
Assigned value : 570.4
Target concentration : 57.04
Corrected concentration : 616
Recovery : 107.99439
Sample: 4 | Dilution factor: 10
Replicates : 1
Mean result : 66.2
SD result : NA
CV result : NA
Specimen content : 10
Assigned value : 625.6
Target concentration : 62.56
Corrected concentration : 662
Recovery : 105.81841
Sample: 5 | Dilution factor: 10
Replicates : 1
Mean result : 53.4
SD result : NA
CV result : NA
Specimen content : 10
Assigned value : 561.2
Target concentration : 56.12
Corrected concentration : 534
Recovery : 95.153243
Sample: 1 | Dilution factor: 20
Replicates : 1
Mean result : 27.2
SD result : NA
CV result : NA
Specimen content : 5
Assigned value : 506
Target concentration : 25.3
Corrected concentration : 544
Recovery : 107.50988
Sample: 2 | Dilution factor: 20
Replicates : 1
Mean result : 27
SD result : NA
CV result : NA
Specimen content : 5
Assigned value : 598
Target concentration : 29.9
Corrected concentration : 540
Recovery : 90.301003
Sample: 3 | Dilution factor: 20
Replicates : 1
Mean result : 31.3
SD result : NA
CV result : NA
Specimen content : 5
Assigned value : 570.4
Target concentration : 28.52
Corrected concentration : 626
Recovery : 109.74755
Sample: 4 | Dilution factor: 20
Replicates : 1
Mean result : 31.1
SD result : NA
CV result : NA
Specimen content : 5
Assigned value : 625.6
Target concentration : 31.28
Corrected concentration : 622
Recovery : 99.424552
Sample: 5 | Dilution factor: 20
Replicates : 1
Mean result : 25.8
SD result : NA
CV result : NA
Specimen content : 5
Assigned value : 561.2
Target concentration : 28.06
Corrected concentration : 516
Recovery : 91.94583代码
plot(ep34_table2_result, type = "summary")
| 标准位置 | 统计量 | 标准结果 | ivdtools结果 |
|---|---|---|---|
| neat | mean_recovery | 100.00 | 100.000 |
| neat | lower_ci | 100.00 | 100.000 |
| neat | upper_ci | 100.00 | 100.000 |
| 1/2 | mean_recovery | 100.53 | 100.531 |
| 1/2 | lower_ci | 96.16 | 96.157 |
| 1/2 | upper_ci | 104.90 | 104.904 |
| 1/4 | mean_recovery | 102.75 | 102.748 |
| 1/4 | lower_ci | 96.17 | 96.165 |
| 1/4 | upper_ci | 109.33 | 109.331 |
| 1/10 | mean_recovery | 101.82 | 101.814 |
| 1/10 | lower_ci | 91.58 | 91.575 |
| 1/10 | upper_ci | 112.06 | 112.054 |
| 1/20 | mean_recovery | 99.76 | 99.786 |
| 1/20 | lower_ci | 88.76 | 88.847 |
| 1/20 | upper_ci | 110.77 | 110.725 |
1/2 和 1/4 稀释的 95% CI 位于示例的 90%～110% 范围内；1/10 和 1/20 稀释的区间越过该范围。直接计算与原文的细小差异来自原文对样本靶值和中间统计量的显示舍入。
8.2.3 CLSI EP34 表 3：基础加标回收
表 3 在 3 份血清样本中分别加入 0.1 mL、40 mg/dL 的钙加标液或等体积纯溶剂，每个条件测量 2 次。原文把最终混合液中的理论加入浓度显示为 3.64 mg/dL，并用该显示值计算回收率。
代码
ep34_table3_added <- spike_concentration(
sample_concentration = 0,
sample_volume = 1,
stock_concentration = 40,
spike_volume = 0.1
)
ep34_table3_added
Spike concentration
Sample concentration: 0
Stock concentration : 40
Added concentration : 3.6363636
Final concentration : 3.6363636
Sample volume : 1
Spike volume : 0.1
Total volume : 1.1
Spike fraction : 0.090909091代码
ep34_table3 <- read_csv(
"./data/008-稀释回收与HOOK/std-ep34-table3-spike-recovery.csv",
show_col_types = FALSE
)
head(ep34_table3, 6)# A tibble: 6 × 4
sample condition replicate result
<dbl> <chr> <dbl> <dbl>
1 1 solvent 1 9.7
2 1 solvent 2 9.9
3 1 analyte 1 12.9
4 1 analyte 2 13.3
5 2 solvent 1 9.5
6 2 solvent 2 9.5代码
ep34_table3_result <- spike_recovery(
ep34_table3,
sample = "sample",
result = "result",
condition = "condition",
analyte_level = "analyte",
solvent_level = "solvent",
added_concentration = 3.64,
conf.level = 0.95
)
ep34_table3_result
Spike recovery
Samples: 3
Confidence level: 95.0%
Samples : 3
Mean recovery : 90.659341
SD of recovery : 2.7472527
SE of recovery : 1.5861271
Degrees of freedom : 2
CI lower : 83.834787
CI upper : 97.483895
Sample results
Sample: 1
Analyte replicates : 2
Analyte mean : 13.1
Analyte SD : 0.28284271
Solvent replicates : 2
Solvent mean : 9.8
Solvent SD : 0.14142136
Observed increase : 3.3
Added concentration : 3.64
Recovery : 90.659341
Sample: 2
Analyte replicates : 2
Analyte mean : 12.7
Analyte SD : 0.14142136
Solvent replicates : 2
Solvent mean : 9.5
Solvent SD : 0
Observed increase : 3.2
Added concentration : 3.64
Recovery : 87.912088
Sample: 3
Analyte replicates : 2
Analyte mean : 12.3
Analyte SD : 0.14142136
Solvent replicates : 2
Solvent mean : 8.9
Solvent SD : 0.28284271
Observed increase : 3.4
Added concentration : 3.64
Recovery : 93.406593代码
plot(ep34_table3_result)
| 标准位置 | 统计量 | 标准结果 | ivdtools结果 |
|---|---|---|---|
| 1 | recovery | 90.7 | 90.659 |
| 2 | recovery | 88.0 | 87.912 |
| 3 | recovery | 93.4 | 93.407 |
| all | mean_recovery | 90.7 | 90.659 |
三份样本的回收率约为 90.7%、87.9% 和 93.4%，跨样本均值约为 90.7%。标准表只显示一位小数，且中间量的舍入并不完全一致，因此核对容差设为 0.1 个百分点；正式分析应使用未舍入的理论加入浓度和测量结果。
8.2.4 CLSI EP34 表 4：单样本多浓度加标
表 4 将 100 µL、浓度为 1 000 ng/mL 的患者样本与 900 µL 不同浓度的加标液混合。 spike_concentration() 复算质量平衡后的理论浓度；原文没有匹配的溶剂对照重复结果，因此本案例不调用 spike_recovery()。
代码
ep34_table4 <- read_csv(
"./data/008-稀释回收与HOOK/std-ep34-table4-single-spike.csv",
show_col_types = FALSE
)
ep34_table4_balance <- spike_concentration(
sample_concentration = 1000,
sample_volume = 0.1,
stock_concentration = ep34_table4$spike_concentration,
spike_volume = 0.9
)
ep34_table4$computed_ivdtools <- ep34_table4_balance$final_concentration
ep34_table4$recovery_ivdtools <-
100 * ep34_table4$measured_concentration / ep34_table4$computed_ivdtools
ep34_table4# A tibble: 5 × 6
spike_concentration computed_concentration measured_concentration
<dbl> <dbl> <dbl>
1 0 100 94
2 10 109 99
3 100 190 181
4 1000 1000 917
5 10000 9100 9024
# ℹ 3 more variables: standard_recovery <dbl>, computed_ivdtools <dbl>,
# recovery_ivdtools <dbl>| 标准位置 | 统计量 | 标准结果 | ivdtools结果 |
|---|---|---|---|
| 0 | computed_concentration | 100 | 100.000 |
| 0 | recovery | 94 | 94.000 |
| 10 | computed_concentration | 109 | 109.000 |
| 10 | recovery | 91 | 90.826 |
| 100 | computed_concentration | 190 | 190.000 |
| 100 | recovery | 95 | 95.263 |
| 1000 | computed_concentration | 1000 | 1000.000 |
| 1000 | recovery | 92 | 91.700 |
| 10000 | computed_concentration | 9100 | 9100.000 |
| 10000 | recovery | 99 | 99.165 |
10 000 ng/mL 加标液制得的样本理论浓度为 9 100 ng/mL，已超过示例 AMI，需要通过已建立的 EMI 测量。
8.2.5 CLSI EP34 表 5～6：手工稀释方案验证
该案例使用 5 份经参考测量程序赋值的患者样本。两名实验人员各独立制备两份 1/20 稀释样本，每份测量两次，因此每份原样共有 8 个稀释结果。
代码
ep34_table5 <- read_csv(
"./data/008-稀释回收与HOOK/std-ep34-table5-manual-validation.csv",
show_col_types = FALSE
)
head(ep34_table5, 6)# A tibble: 6 × 7
sample assigned scientist preparation replicate result dilution_factor
<dbl> <dbl> <dbl> <dbl> <dbl> <dbl> <dbl>
1 1 140. 1 1 1 6.99 20
2 1 140. 1 1 2 6.51 20
3 1 140. 1 2 1 6.37 20
4 1 140. 1 2 2 6.12 20
5 1 140. 2 1 1 6.53 20
6 1 140. 2 1 2 6.74 20代码
ep34_table5_result <- dilution_recovery(
ep34_table5,
sample = "sample",
result = "result",
dilution_factor = "dilution_factor",
assigned = "assigned",
conf.level = 0.95
)
ep34_table5_result
Dilution recovery
Samples: 5
Dilution factors: 20
Confidence level: 95.0%
Dilution factor: 20
Specimen content : 5
Samples : 5
Mean recovery : 98.761501
SD recovery : 4.0632964
SE recovery : 1.8171614
Degrees of freedom : 4
CI lower : 93.716252
CI upper : 103.80675
Sample results
Sample: 1 | Dilution factor: 20
Replicates : 8
Mean result : 6.65625
SD result : 0.32845689
CV result : 4.9345636
Specimen content : 5
Assigned value : 139.68
Target concentration : 6.984
Corrected concentration : 133.125
Recovery : 95.307131
Sample: 2 | Dilution factor: 20
Replicates : 8
Mean result : 15.23875
SD result : 0.67979908
CV result : 4.4609898
Specimen content : 5
Assigned value : 292.04
Target concentration : 14.602
Corrected concentration : 304.775
Recovery : 104.3607
Sample: 3 | Dilution factor: 20
Replicates : 8
Mean result : 31.73875
SD result : 2.1664879
CV result : 6.8260025
Specimen content : 5
Assigned value : 647.32
Target concentration : 32.366
Corrected concentration : 634.775
Recovery : 98.06201
Sample: 4 | Dilution factor: 20
Replicates : 8
Mean result : 53.6675
SD result : 1.979623
CV result : 3.6886812
Specimen content : 5
Assigned value : 1132.45
Target concentration : 56.6225
Corrected concentration : 1073.35
Recovery : 94.781227
Sample: 5 | Dilution factor: 20
Replicates : 8
Mean result : 92.41375
SD result : 2.4947198
CV result : 2.6995115
Specimen content : 5
Assigned value : 1824.62
Target concentration : 91.231
Corrected concentration : 1848.275
Recovery : 101.29643代码
plot(ep34_table5_result, type = "observed")
| 标准位置 | 统计量 | 标准结果 | ivdtools结果 |
|---|---|---|---|
| 1 | mean | 6.66 | 6.656 |
| 1 | corrected_concentration | 133.13 | 133.125 |
| 1 | recovery | 95.30 | 95.307 |
| 2 | mean | 15.24 | 15.239 |
| 2 | corrected_concentration | 304.78 | 304.775 |
| 2 | recovery | 104.40 | 104.361 |
| 3 | mean | 31.74 | 31.739 |
| 3 | corrected_concentration | 634.78 | 634.775 |
| 3 | recovery | 98.10 | 98.062 |
| 4 | mean | 53.67 | 53.667 |
| 4 | corrected_concentration | 1073.35 | 1073.350 |
| 4 | recovery | 94.80 | 94.781 |
| 5 | mean | 92.41 | 92.414 |
| 5 | corrected_concentration | 1848.28 | 1848.275 |
| 5 | recovery | 101.30 | 101.296 |
五份样本的稀释回收率为 94.8%～104.4%，均位于案例预设的 90%～110% 范围内。这里的 assigned 是参考测量程序赋值。
8.2.6 CLSI EP34 表 7～8：自动稀释方案验证
该案例的 AMI 为 5～40 pg/mL，拟建立 40～80 pg/mL 的 EMI。5 份已通过加标回收表征的样本在两台仪器上各进行 4 次 1/2 自动稀释测量。
代码
ep34_table7 <- read_csv(
"./data/008-稀释回收与HOOK/std-ep34-table7-auto-validation.csv",
show_col_types = FALSE
)
head(ep34_table7, 6)# A tibble: 6 × 6
sample assigned instrument replicate result dilution_factor
<dbl> <dbl> <dbl> <dbl> <dbl> <dbl>
1 1 44.9 1 1 20.3 2
2 1 44.9 1 2 26.0 2
3 1 44.9 1 3 24.3 2
4 1 44.9 1 4 25.0 2
5 1 44.9 2 1 22.5 2
6 1 44.9 2 2 21.3 2代码
ep34_table7_result <- dilution_recovery(
ep34_table7,
sample = "sample",
result = "result",
dilution_factor = "dilution_factor",
assigned = "assigned",
conf.level = 0.95
)
ep34_table7_result
Dilution recovery
Samples: 5
Dilution factors: 2
Confidence level: 95.0%
Dilution factor: 2
Specimen content : 50
Samples : 5
Mean recovery : 104.55585
SD recovery : 6.022583
SE recovery : 2.693381
Degrees of freedom : 4
CI lower : 97.077824
CI upper : 112.03387
Sample results
Sample: 1 | Dilution factor: 2
Replicates : 8
Mean result : 23.6775
SD result : 2.1002432
CV result : 8.8702067
Specimen content : 50
Assigned value : 44.92
Target concentration : 22.46
Corrected concentration : 47.355
Recovery : 105.42075
Sample: 2 | Dilution factor: 2
Replicates : 8
Mean result : 26.44
SD result : 1.9634299
CV result : 7.4259831
Specimen content : 50
Assigned value : 53.78
Target concentration : 26.89
Corrected concentration : 52.88
Recovery : 98.326515
Sample: 3 | Dilution factor: 2
Replicates : 8
Mean result : 35.44125
SD result : 1.9058139
CV result : 5.3773892
Specimen content : 50
Assigned value : 62.32
Target concentration : 31.16
Corrected concentration : 70.8825
Recovery : 113.73957
Sample: 4 | Dilution factor: 2
Replicates : 8
Mean result : 35.975
SD result : 1.3997653
CV result : 3.8909389
Specimen content : 50
Assigned value : 68.34
Target concentration : 34.17
Corrected concentration : 71.95
Recovery : 105.28241
Sample: 5 | Dilution factor: 2
Replicates : 8
Mean result : 37.50875
SD result : 1.5492066
CV result : 4.1302539
Specimen content : 50
Assigned value : 75.01
Target concentration : 37.505
Corrected concentration : 75.0175
Recovery : 100.01| 标准位置 | 统计量 | 标准结果 | ivdtools结果 |
|---|---|---|---|
| 1 | mean | 23.68 | 23.678 |
| 1 | corrected_concentration | 47.36 | 47.355 |
| 1 | recovery | 105.40 | 105.421 |
| 2 | mean | 26.44 | 26.440 |
| 2 | corrected_concentration | 52.88 | 52.880 |
| 2 | recovery | 98.30 | 98.327 |
| 3 | mean | 35.44 | 35.441 |
| 3 | corrected_concentration | 70.88 | 70.882 |
| 3 | recovery | 113.70 | 113.740 |
| 4 | mean | 35.98 | 35.975 |
| 4 | corrected_concentration | 71.95 | 71.950 |
| 4 | recovery | 105.30 | 105.282 |
| 5 | mean | 37.51 | 37.509 |
| 5 | corrected_concentration | 75.02 | 75.018 |
| 5 | recovery | 100.00 | 100.010 |
五份样本的回收率为 98.3%～113.7%，均位于案例预设的 85%～115% 范围内。
8.2.7 CLSI EP34 附录 C：两组完整稀释分析
附录 C 表 C1 和 C2 只公布每份样本在各稀释水平的观测均值，没有公布均值背后的单次结果。本节按原文粒度输入，分别复算分析物 B 和分析物 C 的跨样本回收率。
表 C1：分析物 B
代码
ep34_c1 <- read_csv(
"./data/008-稀释回收与HOOK/std-ep34-appendix-c1.csv",
show_col_types = FALSE
)
head(ep34_c1, 6)# A tibble: 6 × 5
sample dilution dilution_factor assigned observed_mean
<dbl> <chr> <dbl> <dbl> <dbl>
1 1 neat 1 220. 220.
2 1 1/2 2 220. 115.
3 1 1/4 4 220. 58.2
4 1 1/10 10 220. 25.6
5 1 1/20 20 220. 15.7
6 2 neat 1 260. 260. 代码
ep34_c1_result <- dilution_recovery(
ep34_c1,
sample = "sample",
result = "observed_mean",
dilution_factor = "dilution_factor",
assigned = "assigned",
conf.level = 0.95
)
ep34_c1_result
Dilution recovery
Samples: 5
Dilution factors: 1, 2, 4, 10, 20
Confidence level: 95.0%
Dilution factor: 1
Specimen content : 100
Samples : 5
Mean recovery : 100
SD recovery : 0
SE recovery : 0
Degrees of freedom : 4
CI lower : 100
CI upper : 100
Dilution factor: 2
Specimen content : 50
Samples : 5
Mean recovery : 100.49583
SD recovery : 3.5627839
SE recovery : 1.5933254
Degrees of freedom : 4
CI lower : 96.072052
CI upper : 104.91961
Dilution factor: 4
Specimen content : 25
Samples : 5
Mean recovery : 104.98711
SD recovery : 2.8223671
SE recovery : 1.2622009
Degrees of freedom : 4
CI lower : 101.48268
CI upper : 108.49154
Dilution factor: 10
Specimen content : 10
Samples : 5
Mean recovery : 115.13247
SD recovery : 3.1142636
SE recovery : 1.392741
Degrees of freedom : 4
CI lower : 111.2656
CI upper : 118.99934
Dilution factor: 20
Specimen content : 5
Samples : 5
Mean recovery : 135.48746
SD recovery : 8.945831
SE recovery : 4.0006973
Degrees of freedom : 4
CI lower : 124.37974
CI upper : 146.59517
Sample results
Sample: 1 | Dilution factor: 1
Replicates : 1
Mean result : 220.3
SD result : NA
CV result : NA
Specimen content : 100
Assigned value : 220.3
Target concentration : 220.3
Corrected concentration : 220.3
Recovery : 100
Sample: 2 | Dilution factor: 1
Replicates : 1
Mean result : 260.1
SD result : NA
CV result : NA
Specimen content : 100
Assigned value : 260.1
Target concentration : 260.1
Corrected concentration : 260.1
Recovery : 100
Sample: 3 | Dilution factor: 1
Replicates : 1
Mean result : 248
SD result : NA
CV result : NA
Specimen content : 100
Assigned value : 248
Target concentration : 248
Corrected concentration : 248
Recovery : 100
Sample: 4 | Dilution factor: 1
Replicates : 1
Mean result : 272.2
SD result : NA
CV result : NA
Specimen content : 100
Assigned value : 272.2
Target concentration : 272.2
Corrected concentration : 272.2
Recovery : 100
Sample: 5 | Dilution factor: 1
Replicates : 1
Mean result : 244
SD result : NA
CV result : NA
Specimen content : 100
Assigned value : 244
Target concentration : 244
Corrected concentration : 244
Recovery : 100
Sample: 1 | Dilution factor: 2
Replicates : 1
Mean result : 114.8
SD result : NA
CV result : NA
Specimen content : 50
Assigned value : 220.3
Target concentration : 110.15
Corrected concentration : 229.6
Recovery : 104.22152
Sample: 2 | Dilution factor: 2
Replicates : 1
Mean result : 128.2
SD result : NA
CV result : NA
Specimen content : 50
Assigned value : 260.1
Target concentration : 130.05
Corrected concentration : 256.4
Recovery : 98.57747
Sample: 3 | Dilution factor: 2
Replicates : 1
Mean result : 127.3
SD result : NA
CV result : NA
Specimen content : 50
Assigned value : 248
Target concentration : 124
Corrected concentration : 254.6
Recovery : 102.66129
Sample: 4 | Dilution factor: 2
Replicates : 1
Mean result : 129.7
SD result : NA
CV result : NA
Specimen content : 50
Assigned value : 272.2
Target concentration : 136.1
Corrected concentration : 259.4
Recovery : 95.297575
Sample: 5 | Dilution factor: 2
Replicates : 1
Mean result : 124.1
SD result : NA
CV result : NA
Specimen content : 50
Assigned value : 244
Target concentration : 122
Corrected concentration : 248.2
Recovery : 101.72131
Sample: 1 | Dilution factor: 4
Replicates : 1
Mean result : 58.2
SD result : NA
CV result : NA
Specimen content : 25
Assigned value : 220.3
Target concentration : 55.075
Corrected concentration : 232.8
Recovery : 105.67408
Sample: 2 | Dilution factor: 4
Replicates : 1
Mean result : 67.1
SD result : NA
CV result : NA
Specimen content : 25
Assigned value : 260.1
Target concentration : 65.025
Corrected concentration : 268.4
Recovery : 103.19108
Sample: 3 | Dilution factor: 4
Replicates : 1
Mean result : 66.3
SD result : NA
CV result : NA
Specimen content : 25
Assigned value : 248
Target concentration : 62
Corrected concentration : 265.2
Recovery : 106.93548
Sample: 4 | Dilution factor: 4
Replicates : 1
Mean result : 68.8
SD result : NA
CV result : NA
Specimen content : 25
Assigned value : 272.2
Target concentration : 68.05
Corrected concentration : 275.2
Recovery : 101.10213
Sample: 5 | Dilution factor: 4
Replicates : 1
Mean result : 65.9
SD result : NA
CV result : NA
Specimen content : 25
Assigned value : 244
Target concentration : 61
Corrected concentration : 263.6
Recovery : 108.03279
Sample: 1 | Dilution factor: 10
Replicates : 1
Mean result : 25.6
SD result : NA
CV result : NA
Specimen content : 10
Assigned value : 220.3
Target concentration : 22.03
Corrected concentration : 256
Recovery : 116.20517
Sample: 2 | Dilution factor: 10
Replicates : 1
Mean result : 28.8
SD result : NA
CV result : NA
Specimen content : 10
Assigned value : 260.1
Target concentration : 26.01
Corrected concentration : 288
Recovery : 110.72664
Sample: 3 | Dilution factor: 10
Replicates : 1
Mean result : 29.6
SD result : NA
CV result : NA
Specimen content : 10
Assigned value : 248
Target concentration : 24.8
Corrected concentration : 296
Recovery : 119.35484
Sample: 4 | Dilution factor: 10
Replicates : 1
Mean result : 31.2
SD result : NA
CV result : NA
Specimen content : 10
Assigned value : 272.2
Target concentration : 27.22
Corrected concentration : 312
Recovery : 114.6216
Sample: 5 | Dilution factor: 10
Replicates : 1
Mean result : 28
SD result : NA
CV result : NA
Specimen content : 10
Assigned value : 244
Target concentration : 24.4
Corrected concentration : 280
Recovery : 114.7541
Sample: 1 | Dilution factor: 20
Replicates : 1
Mean result : 15.7
SD result : NA
CV result : NA
Specimen content : 5
Assigned value : 220.3
Target concentration : 11.015
Corrected concentration : 314
Recovery : 142.53291
Sample: 2 | Dilution factor: 20
Replicates : 1
Mean result : 17.4
SD result : NA
CV result : NA
Specimen content : 5
Assigned value : 260.1
Target concentration : 13.005
Corrected concentration : 348
Recovery : 133.79469
Sample: 3 | Dilution factor: 20
Replicates : 1
Mean result : 15.6
SD result : NA
CV result : NA
Specimen content : 5
Assigned value : 248
Target concentration : 12.4
Corrected concentration : 312
Recovery : 125.80645
Sample: 4 | Dilution factor: 20
Replicates : 1
Mean result : 17.5
SD result : NA
CV result : NA
Specimen content : 5
Assigned value : 272.2
Target concentration : 13.61
Corrected concentration : 350
Recovery : 128.58193
Sample: 5 | Dilution factor: 20
Replicates : 1
Mean result : 17.9
SD result : NA
CV result : NA
Specimen content : 5
Assigned value : 244
Target concentration : 12.2
Corrected concentration : 358
Recovery : 146.72131代码
plot(ep34_c1_result, type = "summary")
表 C2：分析物 C
代码
ep34_c2 <- read_csv(
"./data/008-稀释回收与HOOK/std-ep34-appendix-c2.csv",
show_col_types = FALSE
)
head(ep34_c2, 6)# A tibble: 6 × 5
sample dilution dilution_factor assigned observed_mean
<dbl> <chr> <dbl> <dbl> <dbl>
1 1 neat 1 1492. 1492.
2 1 1/2 2 1492. 751.
3 1 1/10 10 1492. 145.
4 1 1/50 50 1492. 28.7
5 1 1/200 200 1492. 7.5
6 2 neat 1 1386. 1386. 代码
ep34_c2_result <- dilution_recovery(
ep34_c2,
sample = "sample",
result = "observed_mean",
dilution_factor = "dilution_factor",
assigned = "assigned",
conf.level = 0.95
)
ep34_c2_result
Dilution recovery
Samples: 6
Dilution factors: 1, 2, 10, 50, 200
Confidence level: 95.0%
Dilution factor: 1
Specimen content : 100
Samples : 6
Mean recovery : 100
SD recovery : 0
SE recovery : 0
Degrees of freedom : 5
CI lower : 100
CI upper : 100
Dilution factor: 2
Specimen content : 50
Samples : 6
Mean recovery : 101.33362
SD recovery : 3.2217773
SE recovery : 1.3152851
Degrees of freedom : 5
CI lower : 97.952571
CI upper : 104.71467
Dilution factor: 10
Specimen content : 10
Samples : 6
Mean recovery : 101.55253
SD recovery : 5.9523994
SE recovery : 2.4300569
Degrees of freedom : 5
CI lower : 95.305866
CI upper : 107.79919
Dilution factor: 50
Specimen content : 2
Samples : 6
Mean recovery : 102.34874
SD recovery : 5.2080713
SE recovery : 2.1261862
Degrees of freedom : 5
CI lower : 96.883208
CI upper : 107.81428
Dilution factor: 200
Specimen content : 0.5
Samples : 6
Mean recovery : 102.55094
SD recovery : 5.5420679
SE recovery : 2.2625397
Degrees of freedom : 5
CI lower : 96.734901
CI upper : 108.36699
Sample results
Sample: 1 | Dilution factor: 1
Replicates : 1
Mean result : 1492.1
SD result : NA
CV result : NA
Specimen content : 100
Assigned value : 1492.1
Target concentration : 1492.1
Corrected concentration : 1492.1
Recovery : 100
Sample: 2 | Dilution factor: 1
Replicates : 1
Mean result : 1386.5
SD result : NA
CV result : NA
Specimen content : 100
Assigned value : 1386.5
Target concentration : 1386.5
Corrected concentration : 1386.5
Recovery : 100
Sample: 3 | Dilution factor: 1
Replicates : 1
Mean result : 1290.8
SD result : NA
CV result : NA
Specimen content : 100
Assigned value : 1290.8
Target concentration : 1290.8
Corrected concentration : 1290.8
Recovery : 100
Sample: 4 | Dilution factor: 1
Replicates : 1
Mean result : 1451.6
SD result : NA
CV result : NA
Specimen content : 100
Assigned value : 1451.6
Target concentration : 1451.6
Corrected concentration : 1451.6
Recovery : 100
Sample: 5 | Dilution factor: 1
Replicates : 1
Mean result : 1209.8
SD result : NA
CV result : NA
Specimen content : 100
Assigned value : 1209.8
Target concentration : 1209.8
Corrected concentration : 1209.8
Recovery : 100
Sample: 6 | Dilution factor: 1
Replicates : 1
Mean result : 1326.4
SD result : NA
CV result : NA
Specimen content : 100
Assigned value : 1326.4
Target concentration : 1326.4
Corrected concentration : 1326.4
Recovery : 100
Sample: 1 | Dilution factor: 2
Replicates : 1
Mean result : 750.9
SD result : NA
CV result : NA
Specimen content : 50
Assigned value : 1492.1
Target concentration : 746.05
Corrected concentration : 1501.8
Recovery : 100.65009
Sample: 2 | Dilution factor: 2
Replicates : 1
Mean result : 680.9
SD result : NA
CV result : NA
Specimen content : 50
Assigned value : 1386.5
Target concentration : 693.25
Corrected concentration : 1361.8
Recovery : 98.218536
Sample: 3 | Dilution factor: 2
Replicates : 1
Mean result : 648.3
SD result : NA
CV result : NA
Specimen content : 50
Assigned value : 1290.8
Target concentration : 645.4
Corrected concentration : 1296.6
Recovery : 100.44933
Sample: 4 | Dilution factor: 2
Replicates : 1
Mean result : 745.2
SD result : NA
CV result : NA
Specimen content : 50
Assigned value : 1451.6
Target concentration : 725.8
Corrected concentration : 1490.4
Recovery : 102.67291
Sample: 5 | Dilution factor: 2
Replicates : 1
Mean result : 598.3
SD result : NA
CV result : NA
Specimen content : 50
Assigned value : 1209.8
Target concentration : 604.9
Corrected concentration : 1196.6
Recovery : 98.908911
Sample: 6 | Dilution factor: 2
Replicates : 1
Mean result : 710.3
SD result : NA
CV result : NA
Specimen content : 50
Assigned value : 1326.4
Target concentration : 663.2
Corrected concentration : 1420.6
Recovery : 107.10193
Sample: 1 | Dilution factor: 10
Replicates : 1
Mean result : 145.4
SD result : NA
CV result : NA
Specimen content : 10
Assigned value : 1492.1
Target concentration : 149.21
Corrected concentration : 1454
Recovery : 97.446552
Sample: 2 | Dilution factor: 10
Replicates : 1
Mean result : 135.8
SD result : NA
CV result : NA
Specimen content : 10
Assigned value : 1386.5
Target concentration : 138.65
Corrected concentration : 1358
Recovery : 97.944464
Sample: 3 | Dilution factor: 10
Replicates : 1
Mean result : 135.7
SD result : NA
CV result : NA
Specimen content : 10
Assigned value : 1290.8
Target concentration : 129.08
Corrected concentration : 1357
Recovery : 105.1286
Sample: 4 | Dilution factor: 10
Replicates : 1
Mean result : 136.5
SD result : NA
CV result : NA
Specimen content : 10
Assigned value : 1451.6
Target concentration : 145.16
Corrected concentration : 1365
Recovery : 94.034169
Sample: 5 | Dilution factor: 10
Replicates : 1
Mean result : 127.2
SD result : NA
CV result : NA
Specimen content : 10
Assigned value : 1209.8
Target concentration : 120.98
Corrected concentration : 1272
Recovery : 105.14135
Sample: 6 | Dilution factor: 10
Replicates : 1
Mean result : 145.4
SD result : NA
CV result : NA
Specimen content : 10
Assigned value : 1326.4
Target concentration : 132.64
Corrected concentration : 1454
Recovery : 109.62002
Sample: 1 | Dilution factor: 50
Replicates : 1
Mean result : 28.7
SD result : NA
CV result : NA
Specimen content : 2
Assigned value : 1492.1
Target concentration : 29.842
Corrected concentration : 1435
Recovery : 96.173179
Sample: 2 | Dilution factor: 50
Replicates : 1
Mean result : 28.5
SD result : NA
CV result : NA
Specimen content : 2
Assigned value : 1386.5
Target concentration : 27.73
Corrected concentration : 1425
Recovery : 102.77678
Sample: 3 | Dilution factor: 50
Replicates : 1
Mean result : 26.8
SD result : NA
CV result : NA
Specimen content : 2
Assigned value : 1290.8
Target concentration : 25.816
Corrected concentration : 1340
Recovery : 103.81159
Sample: 4 | Dilution factor: 50
Replicates : 1
Mean result : 27.9
SD result : NA
CV result : NA
Specimen content : 2
Assigned value : 1451.6
Target concentration : 29.032
Corrected concentration : 1395
Recovery : 96.100854
Sample: 5 | Dilution factor: 50
Replicates : 1
Mean result : 25.9
SD result : NA
CV result : NA
Specimen content : 2
Assigned value : 1209.8
Target concentration : 24.196
Corrected concentration : 1295
Recovery : 107.04249
Sample: 6 | Dilution factor: 50
Replicates : 1
Mean result : 28.7
SD result : NA
CV result : NA
Specimen content : 2
Assigned value : 1326.4
Target concentration : 26.528
Corrected concentration : 1435
Recovery : 108.18758
Sample: 1 | Dilution factor: 200
Replicates : 1
Mean result : 7.5
SD result : NA
CV result : NA
Specimen content : 0.5
Assigned value : 1492.1
Target concentration : 7.4605
Corrected concentration : 1500
Recovery : 100.52946
Sample: 2 | Dilution factor: 200
Replicates : 1
Mean result : 7.2
SD result : NA
CV result : NA
Specimen content : 0.5
Assigned value : 1386.5
Target concentration : 6.9325
Corrected concentration : 1440
Recovery : 103.85864
Sample: 3 | Dilution factor: 200
Replicates : 1
Mean result : 6.4
SD result : NA
CV result : NA
Specimen content : 0.5
Assigned value : 1290.8
Target concentration : 6.454
Corrected concentration : 1280
Recovery : 99.16331
Sample: 4 | Dilution factor: 200
Replicates : 1
Mean result : 7.1
SD result : NA
CV result : NA
Specimen content : 0.5
Assigned value : 1451.6
Target concentration : 7.258
Corrected concentration : 1420
Recovery : 97.823092
Sample: 5 | Dilution factor: 200
Replicates : 1
Mean result : 6.1
SD result : NA
CV result : NA
Specimen content : 0.5
Assigned value : 1209.8
Target concentration : 6.049
Corrected concentration : 1220
Recovery : 100.84311
Sample: 6 | Dilution factor: 200
Replicates : 1
Mean result : 7.5
SD result : NA
CV result : NA
Specimen content : 0.5
Assigned value : 1326.4
Target concentration : 6.632
Corrected concentration : 1500
Recovery : 113.08806代码
plot(ep34_c2_result, type = "summary")
| 标准位置 | 统计量 | 标准结果 | ivdtools结果 |
|---|---|---|---|
| appendix_c1 / neat | mean_recovery | 100.00 | 100.000 |
| appendix_c1 / neat | lower_ci | 100.00 | 100.000 |
| appendix_c1 / neat | upper_ci | 100.00 | 100.000 |
| appendix_c1 / 1/2 | mean_recovery | 100.50 | 100.496 |
| appendix_c1 / 1/2 | lower_ci | 96.06 | 96.072 |
| appendix_c1 / 1/2 | upper_ci | 104.89 | 104.920 |
| appendix_c1 / 1/4 | mean_recovery | 104.99 | 104.987 |
| appendix_c1 / 1/4 | lower_ci | 101.45 | 101.483 |
| appendix_c1 / 1/4 | upper_ci | 108.50 | 108.492 |
| appendix_c1 / 1/10 | mean_recovery | 115.13 | 115.132 |
| appendix_c1 / 1/10 | lower_ci | 111.33 | 111.266 |
| appendix_c1 / 1/10 | upper_ci | 119.05 | 118.999 |
| appendix_c1 / 1/20 | mean_recovery | 135.49 | 135.487 |
| appendix_c1 / 1/20 | lower_ci | 124.43 | 124.380 |
| appendix_c1 / 1/20 | upper_ci | 146.69 | 146.595 |
| appendix_c2 / neat | mean_recovery | 100.00 | 100.000 |
| appendix_c2 / neat | lower_ci | 100.00 | 100.000 |
| appendix_c2 / neat | upper_ci | 100.00 | 100.000 |
| appendix_c2 / 1/2 | mean_recovery | 101.33 | 101.334 |
| appendix_c2 / 1/2 | lower_ci | 97.95 | 97.953 |
| appendix_c2 / 1/2 | upper_ci | 104.71 | 104.715 |
| appendix_c2 / 1/10 | mean_recovery | 101.55 | 101.553 |
| appendix_c2 / 1/10 | lower_ci | 95.31 | 95.306 |
| appendix_c2 / 1/10 | upper_ci | 107.80 | 107.799 |
| appendix_c2 / 1/50 | mean_recovery | 102.35 | 102.349 |
| appendix_c2 / 1/50 | lower_ci | 96.88 | 96.883 |
| appendix_c2 / 1/50 | upper_ci | 107.81 | 107.814 |
| appendix_c2 / 1/200 | mean_recovery | 102.71 | 102.551 |
| appendix_c2 / 1/200 | lower_ci | 96.82 | 96.735 |
| appendix_c2 / 1/200 | upper_ci | 108.60 | 108.367 |
表 C1 的回收率随稀释加深而明显升高，1/10 和 1/20 稀释不能满足示例要求；表 C2 在 1/200 稀释时仍保持相对稳定。表 C2 的最高稀释水平受原文只公布一位小数观测均值影响，软件由显示值重算的汇总与原文存在最多约 0.23 个百分点的差异。
8.2.8 高剂量钩状效应
EP34 的钩状效应图只给出示意轨迹，没有逐浓度原始响应。下面使用教学数据演示 hook_effect(),这些数值不来自标准原文。
代码
hook_data <- expand.grid(
concentration = c(1, 2, 3, 4, 5, 6, 7, 8),
replicate = 1:3,
KEEP.OUT.ATTRS = FALSE
)
hook_mean <- c(100000, 150000, 180000, 178000, 183000, 160000, 110000, 80000)
hook_data$response <-
rep(hook_mean, times = 3) + rep(c(-300, 0, 300), each = 8)
head(hook_data, 6) concentration replicate response
1 1 1 99700
2 2 1 149700
3 3 1 179700
4 4 1 177700
5 5 1 182700
6 6 1 159700代码
hook_result <- hook_effect(
hook_data,
concentration = "concentration",
response = "response",
uloq = 1.5,
uloq_response = 130000,
conf.level = 0.95
)
hook_result
High-dose hook-effect experiment
ULoQ concentration: 1.5
ULoQ response: supplied
Series: 1
Series: all
ULoQ concentration : 1.5
ULoQ response : 130000
Hook concentration : 6
Hook response : 160000
First in-range concentration : 7
First in-range response : 110000
Highest tested concentration : 8
Hook lower bound : NA
Concentration-level results
Series: all | Concentration: 1
Replicates : 3
Mean response : 1e+05
SD response : 300
CV response : 0.3
SE response : 173.20508
CI lower : 99254.759
CI upper : 100745.24
Series: all | Concentration: 2
Replicates : 3
Mean response : 150000
SD response : 300
CV response : 0.2
SE response : 173.20508
CI lower : 149254.76
CI upper : 150745.24
Series: all | Concentration: 3
Replicates : 3
Mean response : 180000
SD response : 300
CV response : 0.16666667
SE response : 173.20508
CI lower : 179254.76
CI upper : 180745.24
Series: all | Concentration: 4
Replicates : 3
Mean response : 178000
SD response : 300
CV response : 0.16853933
SE response : 173.20508
CI lower : 177254.76
CI upper : 178745.24
Series: all | Concentration: 5
Replicates : 3
Mean response : 183000
SD response : 300
CV response : 0.16393443
SE response : 173.20508
CI lower : 182254.76
CI upper : 183745.24
Series: all | Concentration: 6
Replicates : 3
Mean response : 160000
SD response : 300
CV response : 0.1875
SE response : 173.20508
CI lower : 159254.76
CI upper : 160745.24
Series: all | Concentration: 7
Replicates : 3
Mean response : 110000
SD response : 300
CV response : 0.27272727
SE response : 173.20508
CI lower : 109254.76
CI upper : 110745.24
Series: all | Concentration: 8
Replicates : 3
Mean response : 80000
SD response : 300
CV response : 0.375
SE response : 173.20508
CI lower : 79254.759
CI upper : 80745.241代码
plot(hook_result)
本例在 7 的已测浓度首次回落至 ULoQ 响应范围内，因此函数把前一个已测浓度 6 报告为 hook_concentration。该结果是由试验浓度间距限定的界限，不是转折点。