An AI Walk from Pharmacokinetics to Marketing (Artificial Intelligence)

INTRODUCTION

This work is intended for providing a review of real-life practical applications of Artificial Intelligence (AI) methods. We focus on the use of Machine Learning (ML) methods applied to rather real problems than synthetic problems with standard and controlled environment. In particular, we will describe the following problems in next sections:

• Optimization of Erythropoietin (EPO) dosages in anaemic patients undergoing Chronic Renal Failure (CRF).

• Optimization of a recommender system for citizen web portal users.

• Optimization of a marketing campaign.

The choice of these problems is due to their relevance and their heterogeneity. This heterogeneity shows the capabilities and versatility of ML methods to solve real-life problems in very different fields of knowledge. The following methods will be mentioned during this work:

• Artificial Neural Networks (ANNs): Multilayer Perceptron (MLP), Finite Impulse Response (FIR) Neural Network, Elman Network, Self-Oganizing Maps (SOMs) and Adaptive Resonance Theory (ART).

• Other clustering algorithms: K-Means, Expectation-Maximization (EM) algorithm, Fuzzy C-Means (FCM), Hierarchical Clustering Algorithms (HCA).

• Generalized Auto-Regressive Conditional Het-eroskedasticity (GARCH).

• Support Vector Regression (SVR).

• Collaborative filtering techniques.

• Reinforcement Learning (RL) methods.


BACKGROUND

The aim of this communication is to emphasize the capabilities of ML methods to deliver practical and effective solutions in difficult real-world applications. In order to make the work easy to read we focus on each of the three separate domains, namely, Pharmacokinetics (PK), Web Recommender Systems and Marketing.

Pharmacokinetics

Clinical decision-making support systems have used Artificial Intelligence (AI) methods since the end of the fifties. Nevertheless, it was only during the nineties that decision support systems were routinely used in clinical practice on a significant scale. In particular, ANNs have been widely used in medical applications the last two decades (Lisboa, 2002). One of the first relevant studies involving ANNs and Therapeutic Drug Monitoring was (Gray, Ash, Jacobi, & Michel, 1991). In this work, an ANN-based drug interaction warning system was developed with a computerized real-time entry medical records system. A reference work in this field is found in (Brier, Zurada, & Aronoff, 1995), in which the capabilities of ANNs and NONMEN are benchmarked.

Focusing on problems that are closer to the real-life application that will be described in next section, there are also a number of recent works involving the use of ML for drug delivery in kidney disease. For instance, a comparison of renal-related adverse drug reactions between rofecoxib and celecoxib, based on the WHO/Uppsala Monitoring Centre safety database, was carried out by (Zhao, Reynolds, Lejkowith, Whelton, & Arellano, 2001). Disproportionality in the association between a particular drug and renal-related adverse drug reactions was evaluated using a Bayesian confidence propagation neural network method. A study of prediction of cyclosporine dosage in patients after kidney transplantation using neural networks and kernel-based methods was carried out in (Camps et al., 2003). In (Gaweda, Jacobs, Brier, & Zurada, 2003), a pharmacodynamic population analysis in CRF patients using ANNs was performed. Such models allow for adjusting the dosing regime. Finally, in (Martin et al., 2003) , the use of neural networks was proposed for the optimization of EPO dosage in patients undergoing anaemia connected with CRF.

Web Recommender Systems

Recommender systems are widely used in web sites including Google. The main goal of these systems is to recommend obj ects which a user might be interested in. Two main approaches have been used: content-based and collaborative filtering (Zukerman & Albrecht, 2001), although other kinds of techniques have also been proposed (Burke, 2002).

Collaborative recommenders aggregate ratings of recommendations of objects, find user similarities based on their ratings, and finally provide new recommendations based on inter-user comparisons. Some of the most relevant systems using this technique are GroupLens/NetPerceptions and Recommender. The main advantage of collaborative techniques is that they are independent from any machine-readable representation of the objects, and that they work well for complex objects where subjective judgements are responsible for much of the variation in preferences.

Content-based learning is used when a user’s past behaviour is a reliable indicator of his/her future behaviour. It is particularly suitable for situations in which users tend to exhibit idiosyncratic behaviour. However, this approach requires a system to collect relatively large amounts of data from each user in order to enable the formulation of a statistical model. Examples of systems of this kind are text recommendation systems like the newsgroup filtering system, NewsWeeder, which uses words from its texts as features.

Marketing

The latest marketing trends are more concerned about maintaining current customers and optimizing their behaviour than getting new ones. For this reason, relational marketing focuses on what a company must do to achieve this obj ective. The relationships between a company and its costumers follow a sequence of action-response system, where the customers can modify their behaviour in accordance with the marketing actions developed by the company.

The development of a good and individualized policy is not easy because there are many variables to take into account. Applications of this kind can be viewed as a Markov chain problem, in which a company decides what action to take once the customer properties in the current state (time t), are known. Reinforcement Learning (RL) can be used to solve this task since previous applications have demonstrated its suitability in this area. In (Sun, 2003), RL was applied to analyse mailing by studying how an action in time t influences actions in following times. In (Abe et al., 2002) and (Pednault, Abe & Zadrozny., 2002), several RL algorithms were benchmarked in mailing problems. In (Abe, 2004), RL was used to optimize cross channel marketing.

AI CONTRIBUTIONS IN REAL-LIFE APPLICATIONS

Previous section showed a review of related work. In this section, we will focus on showing authors’ experience in using AI to solve real-life problems. In order to show up the versatility of AI methods, we will focus on particular applications from three different fields of knowledge, the same that were reviewed in previous section.

Pharmacokinetics

Although we have also worked with other pharmacokinetic problems, in this work, we focus on maybe the most relevant problem, which is the optimization of EPO dosages in patients within a haemodialysis program. Patients who suffer from CRF tend to suffer from an associated anaemia, as well. EPO is the treatment of choice for this kind of anaemia. The use of this drug has greatly reduced cardiovascular problems and the necessity of multiple transfusions. However, EPO is expensive, making the already costly CRF program even more so. Moreover, there are significant risks associated with EPO such as thrombo-embolisms and vascular problems, if Haemoglobin (Hb) levels are too high or they increase too fast. Consequently, optimizing dosage is critical to ensure adequate pharmacotherapy as well as a reasonable treatment cost.

Population models, widely used by Pharmacoki-netics’ researchers, are not suitable for this problem since the response to the treatment with EPO is highly dependent on the patient. The same dosages may have very different responses in different patients, most notably the so-called EPO-resistant patients, who do not respond to EPO treatment, even after receiving high dosages. Therefore, it is preferable to focus on an individualized treatment.

Our first approach to this problem was based on predicting the Hb level given a certain administered dose of EPO. Although the final goal is to individualize EPO doses, we did not predict EPO dose but Hb level. The reason is that EPO predictors would model physician’s protocol whereas Hb predictors model body’s response to the treatment, hence being a more “objective” approach. In particular, the following models were used: GARCH (Hamilton, 1994), MLP, FIR neural network, Elman’s recurrent neural network and SVR (Haykin, 1999). Accurate prediction models were obtained, especially when using ANNs and SVR. Dynamic neural networks (i.e., FIR and recurrent) did not outperform notably the static MLP probably due to the short length of the time series (Martin et al., 2003). An easy-to-use software application was developed to be used by clinicians, in which after filling in patients’ data and a certain EPO dose, the predicted Hb level for next month was shown.

Although prediction models were accurate, we realized that this prediction approach had a major flaw. Despite obtaining accurate models, we had not yet achieved a straightforward way to transfer the extracted knowledge to daily clinical practice, because clinicians had to “play” with different doses to analyse the best solution to attain a certain Hb level. It would be better to have an automatic model that suggests the actions to be made in order to attain the targeted range of Hb, rather than this “indirect” approach. This reflection made us research on new models, and we came up with the use of RL (Sutton & Barto, 1998). We are currently working on this topic but we have already achieved promising results, finding policies (sequence of actions) that appear to be better than those followed in the hospital, i.e., there are a higher number of patients within the desired target of Hb at the end of the treatment (Martin et al., 2006a).

Web Recommender Systems

A completely different application is described in this subsection, namely, the development of web recommender systems. The authors proposed a new approach to develop recommender systems based on collaborative filtering, but also including an analysis of the feasibility of the recommender by using a prediction stage (Martin et al., 2006b).

The very basic idea was to use clustering algorithms in order to find groups of similar users. The following clustering algorithms were taken into account: K-Means, FCM, HCA, EM algorithm, SOMs and ART. New users were assigned to one of the groups found by these clustering algorithms, and then they were recommended with web services that were usually accessed by other users of his/her same group, but had not yet been accessed by these new users (in order to maximize the usefulness of the approach). Using controlled data sets, the study concluded that ART and SOMs showed a very good behaviour with data sets of very different characteristics, whereas HCA and EM showed an acceptable behaviour provided that the dimensionality of the data set was not too high and the overlap was slight. Algorithms based on K-Means achieved the most limited success in the acceptance of offered recommendations.

Even though the use of RL was only slightly studied, it seems to be a suitable choice for this problem, since the internal dynamics of the problem is easily tackled by RL, and moreover the interference between the recommendation interface and the user can be minimized with an adequate definition of the rewards (Hernandez, Gaudioso, & Boticario, 2004).

Marketing

The last application that will be mentioned in this communication is related to marketing. One way to increase the loyalty of customers is by offering them the opportunity to obtain some gifts as the result of their purchases from a certain company. The company can give virtual credits to anyone who buys certain articles, typically those that the company is interested in promoting. After a certain number of purchases, the customers can exchange their virtual credits for the gifts offered by the company. The problem is to establish the appropriate number of virtual credits for each promoted item. In accordance with the company policy, it is expected that the higher the credit assignment, the higher the amount of purchases. However, the company’s profits are lower since the marketing campaign adds an extra cost to the company. The goal is to achieve a trade-off by establishing an optimal policy.

We proposed a RL approach to optimize this marketing campaign. This particular application, whose characteristics are described below, is much more difficult than the other RL approaches to marketing mentioned in the Background Section. This is basically because there are many more different actions that can be taken. The information used for the study corresponds to five months of the campaign, involving 1,264,862 transactions, 1,004 articles and 3,573 customers.

RL can deal with intrinsic dynamics, and besides, it has the attractive advantage that is able to maximize the so-called long-term reward. This is especially relevant in this application since the company is interested in maximizing the profits at the end of the campaign, and a customer who do not produce much profits in the first months of the campaign, may however make many profitable transactions in the future.

Our first results showed that profits using a policy based on RL instead of the policy followed by the company so far, could even double long-term profits at the end of the campaign (Gomez et al., 2005).

CONCLUSION AND FUTURE TRENDS

This paper has shown the capabilities and versatility of different AI methods to be applied to real-life problems, illustrated with three specific applications in different domains. Clearly, the methodology is generic and applies equally well to many other fields, provided that the information contained in the data is sufficiently rich to require non-linear modelling and is capable of supporting a predictive performance that is of practical value.

As a next future trend, it should be emphasized that AI methods are increasingly popular for business applications in recent years, challenging classical business models.

In the particular case of RL, the commercial potential of this powerful methodology has been significantly underestimated, as it is applied almost exclusively to Robotics. We feel that it is a methodology still to be exploited in many real applications, as we have shown in this paper.

KEY TERMS

Agent: In RL terms, it is the responsible of making decisions according to observations of its environment.

Environment: In RL terms, it is every external condition to the agent.

Exploration-Explotation Dilemma: It is a classical RL dilemma, in which a trade-off solution must be achieved. Exploration means random search of new actions in order to achieve a likely (but yet unknown) better reward than all the known ones, while explotation is focused on exploiting the current knowledge for the maximization of the reward (greedy approach).

Life-Time Value: It is a measure widely used in marketing applications that offers the long-term result that has to be maximized.

Reward: In RL terms, the immediate reward is the value returned by the environment to the agent depending on the taken action. The long-term reward is the sum of all the immediate rewards throughout a complete decision process.

Sensitivity: Similar measure that offers the ratio of positives that are correctly classified by the model. (Refer to Specificity.)

Specificity: Success rate measure in a classification problem. If there are two classes (namely, positive and negative), specificity measures the ratio of negatives that are correctly classified by the model.

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