WHO Collaborating Centre for

International Drug Monitoring

Pattern recognition using a recurrent neural

BACKGROUND Test set. A training set of 8 different patterns within a When ran on the haloperidol cases in the WHO database
A quantitative signal detection method known as the two dimensional 9*9 matrix of units was used and a the following group was highlighted:
BCPNN is routinely used to data mine the WHO database recurrent neural network trained from this data. Rather
(1), for potential drug adverse reaction signals. than using the complete input patterns for training, a Cij i A B C D E F G H I J K L M N O P Q
j Ci/Cj 723 585 517 357 348 270 217 174 174 145 143 ## 108 ## 92 66 60
specified number of units were sampled 2000 times from NMS 723 723 109 171 23 29 126 17 20 11 39 24 27 22 8 43 6 3
HYPERTONIA (B) 585 109 585 121 67 43 88 26 20 13 16 40 24 26 19 17 8 6
each pattern. These 2000 samples were used to train the FEVER (C) 517 171 121 517 33 38 109 18 25 14 47 30 43 35 9 38 3 4
OBJECTIVES network. Noise in the form of additionally highlighted
TREMOR (D)
CONFUSION (E)
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24 348
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CP INCREASED (F) 270 126 88 109 9 25 270 7 13 5 25 14 19 11 5 47 5 5
This poster demonstrates the use of this method to search units was also introduced before training. AGITATION (G) 217 17 26 18 8 39 7 217 6 6 5 10 5 5 4 2 3 2
COMA (H) 174 20 20 25 6 7 13 6 174 19 9 2 5 6 2 1 5 6
for high order quantitative dependencies and robustly, CONVULSIONS (I) 174 11 13 14 11 9 5 6 19 174 3 8 8 1 3 1 1 7
TACHYCARDIA (J) 145 39 16 47 11 14 25 5 9 3 145 6 29 18 2 7 1 1
reproducibly and reliably find and highlight such previously STUPOR (K) 143 24 40 30 12 10 14 10 2 8 6 143 1 5 4 3 2 5
HYPERTENSION (L) 125 27 24 43 8 8 19 5 5 8 29 1 ## 4 2 6 3 1
unknown patterns. The approach is tested on a theoretical SWEATING INCD (M) 108 22 26 35 20 11 11 5 6 1 18 5 4 108 5 3 2 1
1 2 3 DYSPHAGIA (N) 108 8 19 9 8 5 5 4 2 3 2 4 2 5 ## 1 1 2
data set, and its use demonstrated on the WHO database. LEUKOCYTOSIS (0) 92 43 17 38 3 10 47 2 1 1 7 3 6 3 1 92 2 1
URINARY INCONT (P) 66 6 8 3 5 16 5 3 5 1 1 2 3 2 1 2 66 2
The method was chosen as it held the following advantages: APNOEA 60 3 6 4 1 2 5 2 6 7 1 5 1 1 2 1 2 60

1. Could handle discrete variable, where no inherent order The number in each box is the number of cases where both the ADR
of states of a variable exist*. in the column and row were listed with haloperidol as one of the
2. Missing data: Not all information on an individual case 4 5 6 suspected drugs. Each green box represents a positive IC between
will be listed on a case report. The approach should infer the pair of ADRs, and a blue box a negative IC value.
dependencies between variables, even if not reported
together.
3. Unsupervised pattern recognition - patterns should be DISCUSSION
found despite not knowing the type or shape of the Pattern recognition of unknown input patterns, containing
7 8
pattern a priori. both noise and missing data, is a recognised difficult data
4. The method must be robust to noise, that is unrelated mining problem. Vector support methods have been used,
or erroneous inputs. but a data set of mainly discrete variables makes these
methods hard to implement effectively. The results from a
* The WHO database is predominantly made up of such variables. theoretical test show the potential for a Bayesian neural
network approach for recalling previously unknown
METHODS Experiments were run at 10% intervals of noise from 0% to patterns. The results from the WHO database show that
General. A recurrent Bayesian neural network (2) is used; 50%, and completeness from 60%-80%. Each experiment patterns of data can be inferred, which may include
where outputs are recursively fed back to the input layer was ran until a stable pattern resulted, quantitative combinations never reported together on a single case
until a stable output pattern results. All nodes are excited comparison using the ‘hamming distance’ was made to report.
uniformly using a bias of value 1. The outputs are then determine the distance to the nearest initial training pattern. The 17 ADR terms in the above table were those ADR
calculated from the inputs via the weights between the Each experiment was repeated ten times, and positive terms that constituted a stable pattern in the network.
nodes. The activity of each node is then conditioned on the predictive values calculated, to determine our accuracy in These 17 adverse reaction terms have as a group strong
activity of each of the other nodes - the impact that each correctly predicting a trained pattern. independencies within haloperidol reporting. That is the
other node has on the activity of a specific node is given by occurrence on a report of 1 ADR, is likely to imply that 1
the weight between the 2 nodes. The weight is the or more other ADR from this group are also likely to be
information component (IC) between the nodes in the Implemented on WHO database. The network reported.
network. The activity of the node is then in the form of an was set up such that the network was a node for each The table provides a simple approach to visualise the
output layer fed back to the nodes as the input layer. adverse reaction term. The network was then trained using detected pattern.
Iteration by propagation of each output to the other units, all 8468 case reports where haloperidol was suspected of In further work hidden layers will be introduced into
continued until a stable pattern resulted. A stable pattern causing the adverse reaction. A bias of 1 was then added and the neural network architecture to investigate optimising
was defined as such, when the output did not change the network iterated until a stable pattern resulted. the effectiveness of the pattern recognition further, by
beyond a specified level (hamming distance = 0.1) from the detecting higher order dependencies in the data set.
previous output. This method will be used in routine signal detection, and
Results. In all experiments where an input pattern was will be used on all variables in the data set.
A non informative prior is used in the recurrent bayesian sampled then a pattern was recalled. Increasing
network, with a threshold set to prevent the generation of completeness of sampling of the input patterns and
strongly negative weights. This threshold is below the most reduction in noise resulted in fewer erroneous units being REFERENCES
inhibitory weight which highlighted, and fewer cells which should have been 1. Bate A, Lindquist M, Edwards IR, Olsson S, Orre R, Lansner A,
Input Neurons Recurrent
the network can learn highlighted being missed. DeFreitas RM. A Bayesian neural network method for adverse drug
Stimilus Connections
from the data. When ran 10 times for completeness varying from 60 to reaction signal generation.
1 Eur J Clin Pharmacol (1998) 54: 315-321
80%, and from noise 0 to 50% the following units
2. Carl G. Looney, Artificial Neural Network Structures in Pattern
IC14
activated in stable resulting pattern as compared to input
IC12 Recognition Using Neural Networks (1997), Oxford University Press
The picture shows four pattern classified as:
IC13 neurons of a recurrent neural
2
Desired Not desired
network. The neurons get 1 The Uppsala Monitoring Centre, Uppsala. Sweden
Highlighted 5448.2 1328.7
their stimulus from specific Not highlighted 71.8 7731.3 2 Department of Clinical Pharmacology, Umeå University, Umeå, Sweden
input units. Each pair of 3 Department of Mathematical Statistics, Stockholm University,
3 neurons is connected with a Stockholm, Sweden
weight, here denoted IC_ij, Non- integer values result from partial activation of units.
which is the information Overall for these experiments the positive predictive value
The Uppsala Monitoring Centre
component between neuron was 80.4% and the negative predictive value was 99.1%.
4 Stora Torget 3, S-753 20 Uppsala, Sweden
i and j. pij /(pi* pj)
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