AU2011100687A4 - A method of treating a patient - Google Patents

Abstract

The present invention relates to improved methods for delivering a drug such as thalidomide to a patient while reducing the risk of the occurrence of an adverse side 5 effect known or suspected of being caused by the drug. The methods permit the distribution to patients of these drugs, in ways wherein such distribution can be carefully monitored and controlled.

Description

P100/01il Regulation 3.2 AUSTRALIA Patents Act 1990 COMPLETE SPECIFICATION INNOVATION PATENT Invention Title: A method of treating a patient The following statement is a full description of this invention, including the best method of performing it known to us: 2 A method of treating a patient Field of the invention The present invention relates to improved methods for delivering a drug to a patient. Particularly, the present invention relates to methods for delivering a drug to a patient 5 while reducing the risk of the occurrence of an adverse side effect known or suspected of being caused by the drug. More particularly, the drug is a teratogenic or other potentially hazardous drug. The methods permit the distribution to patients of drugs, particularly teratogenic drugs, in ways wherein such distribution can be carefully monitored and controlled. 10 Background of the invention Many beneficial drugs are known or suspected of producing adverse side effects in certain individuals. These side effects may be manifest in the patient taking the drug, in a foetus carried by the patient, or in a recipient (or foetus carried by a recipient) of the bodily fluids of the patient. In some cases, administration of the drug may be acceptable 15 in some patients, but absolutely contraindicated in other patients. For example, drugs known or suspected of causing birth defects if taken by a pregnant woman (i. e. teratogenic drugs), may nonetheless be beneficial for treating certain conditions. However, because of the teratogenic properties of the drug, administration to pregnant women must be avoided. Other drugs are known which may be beneficially 20 employed in the general population, but must be avoided by individuals having a certain preexisting condition, or those concurrently taking certain other medication (s), due to adverse side effects which may develop in those individuals. One such drug which is known to produce adverse side effects, but which may nevertheless be beneficially employed in certain patients is thalidomide. Thalidomide is 25 a drug which was first synthesized in Germany in 1957. Beginning in 1958, it was marketed in many countries for use as a sedative, although it was never approved for use in the United States. After reports of serious birth defects, thalidomide was withdrawn from all markets by 1962. However, during the years it was used, it was 3 found to be effective in treating erythema nodosum leprosum (ENL), a condition of leprosy, and the US Food and Drug Administration (FDA) has made the drug available for this specific use via a program of the Public Health Service. In addition, treatments for other diseases, such as a number of neoplastic diseases including cancers, 5 rheumatoid arthritis, and macular degeneration, are also believed to be possible. The Australian Therapeutic Goods Administration (TGA) has approved an application by Celgene Pty Limited to market thalidomide for the treatment of erythema nodosum leprosum (ENL) and multiple myeloma in specified circumstances. The medical community anticipates that thalidomide will be used for treatment of additional 10 conditions and diseases, including those set forth above. However, due to the severe teratogenic risk of thalidomide, methods are needed to control the distribution of this drug so as to preclude administration to foetuses. In this regard, US Patent No. 6,045,501, to Elsayed et al., provides methods for delivering a drug to a patient while preventing the exposure of a foetus or other 15 contraindicated individual to the drug. US Patent No. 6,315,720, and related cases, to Williams et al., also provides methods for delivering a drug to a patient while preventing the exposure of a foetus or other contraindicated individual to the drug. Lenalidomide is also approved by the TGA for treatment of multiple myeloma (in 20 combination with dexamethasone). Lenalidomide is also indicated for patients with transfusion-dependent anemia due to low- or intermediate-1-risk myelodysplastic syndromes (MDS) associated with a deletion Sq cytogenetic abnormality with or without additional cytogenetic abnormalities. Due to its mechanism of action, a concern exists that lenalidomide may cause birth defects if it is taken during pregnancy. 25 Methods for monitoring and educating patients to whom a drug is distributed have been developed in connection with Accutane (isotretinoin). Accutane, which is a known teratogen, is a uniquely effective drug for the treatment of severe, recalcitrant, nodular acne. A pregnancy prevention program was developed, and the Slone Epidemiology Unit of Boston University designed and implemented a survey to evaluate these efforts.

4 The survey identified relatively low rates of pregnancy during Accutane treatment, which suggests that such a program can be effective. With more than about 325,000 women enrolled to date in the Accutane survey, it is also clear that such a large-scale study can be conducted. Enrollment in the Accutane survey is voluntary, however. Accordingly, 5 assessing the representativeness of the women who have been enrolled in the survey has been problematic, and it has been difficult to determine whether the survey results can be generalized to all female Accutane users. Thus, an improved survey is needed which would be representative of all users of a particular drug, such as thalidomide and lenalidomide, who obtain the drug through 10 legal distribution channels. Mechanisms are also required to ensure compliance with the program or to limit distribution of the drug to participants in the survey. Reference to any prior art in the specification is not, and should not be taken as, an acknowledgment or any form of suggestion that this prior art forms part of the common general knowledge in Australia or any other jurisdiction or that this prior art could 15 reasonably be expected to be ascertained, understood and regarded as relevant by a person skilled in the art. Summary of the invention The present invention is directed to a method of treating a patient with thalidomide by permitting a prescription for thalidomide to be filled by a pharmacy only 20 after a prescription approval code has been communicated to the pharmacy to authorise the dispensing of thalidomide to the patient, comprising the steps of: upon presentation by the patient of the prescription to the pharmacy, consulting a computer readable storage medium in which the patient, a prescriber and the pharmacy are registered, each patient having a unique patient identification number assigned to 25 the patient, and in which is recorded an assessment of whether the risk of an adverse side effect occurring in the patient is acceptable; generating a prescription approval code associated with the presentation by the patient of the prescription for thalidomide upon verifying that: 5 the patient, prescriber and pharmacy are registered in the medium; and the risk of an adverse side effect occurring in the patient for this presentation is acceptable; and communicating the prescription approval code to the pharmacy. 5 In one preferred embodiment, the prescription approval code is generated from a list stored in the computer readable storage medium. In another preferred embodiment the prescription approval code is generated after it is also verified that the patient is not pregnant. In a further preferred embodiment when the patient is a female of childbearing potential, 10 the prescription approval code is issued before the prescription is dispensed. In another embodiment, the method includes the further step of, upon presentation by a patient to a pharmacy of a prescription for lenalidomide to be dispensed, requiring generation of a prescription approval code, wherein the prescription approval code is generated only upon verifying that the patient is registered in the computer readable 15 storage medium using the patient's unique patient identification number. The present invention also relates to a method of reducing the risk of an adverse side effect known or suspected to be caused by a drug occurring in females of childbearing potential receiving the drug directly or indirectly, wherein the drug is thalidomide; the method comprising the steps of: 20 upon presentation by a patient to a pharmacy of a prescription for the drug to be dispensed, requiring the generation of a prescription approval code; wherein the prescription approval code is generated only upon: 6 (i) verifying that the patient is registered in a computer readable storage medium, the patient having a unique patient identification number; and (ii) the pharmacy confirming that the patient has been provided with 5 information about the drug. In one preferred embodiment, the prescription approval code is generated after it is also confirmed that the patient is not pregnant. In another preferred embodiment, when the patient is a female of childbearing potential, the prescription approval code is issued before the prescription is dispensed. 10 In a further preferred embodiment, the method includes the further step of, upon presentation by a patient to a pharmacy of a prescription for lenalidomide to be dispensed, requiring generation of a prescription approval code, wherein the prescription approval code is generated only upon verifying that the patient is registered in the computer readable storage medium using the patient's unique patient 15 identification number. In another embodiment, the patient is registered for lenalidomide in a second computer readable storage medium using the same unique patient identification number. In another preferred embodiment, the adverse side effect is a teratogenic side effect. In a further preferred embodiment, the prescription according to the invention contains 20 the unique patient identification number. The present invention also relates to a system for reducing the risk of an adverse side effect known or suspected to be caused by a drug occurring in females of childbearing potential receiving the drug directly or indirectly, wherein the drug is thalidomide; the system comprising: 7 upon presentation by a patient to a pharmacy of a prescription for the drug to be dispensed, requiring the generation of a prescription approval code; wherein the prescription approval code is generated only upon: (i) verification that the patient is registered in a computer readable 5 storage medium, the patient having a unique patient identification number; and (ii) confirmation from the pharmacy that the patient has been provided with information about the drug. A different form of the invention is directed to a method for dispensing one or more 0 drugs to a patient in need of the drug(s) so as to minimise the risk of an adverse side effect known or suspected of being caused by the drug(s), wherein one of the drugs is thalidomide; the method comprising the steps of: registering a patient, a prescriber and a pharmacy in a computer readable storage medium; 5 assigning a unique patient identification number to the patient; recording in a computer readable storage medium an assessment of whether the risk of an adverse side effect occurring in the patient is acceptable; and generating a prescription approval code associated with each presentation by the patient of a prescription to the pharmacy for dispensing, after consulting a 20 computer readable storage medium that confirms that: the patient, prescriber and pharmacy are registered in the medium; and the risk of an adverse side effect occurring is acceptable.

8 According to one preferred embodiment, the prescription approval code is generated after it is also confirmed that the patient is not pregnant. In another preferred embodiment, when the patient is a female of childbearing potential, the prescription approval code is issued before the prescription is dispensed. 5 In a further preferred embodiment, the method for dispensing the one or more drugs includes the further step of, upon presentation by a patient to a pharmacy of a prescription for lenalidomide to be dispensed, requiring generation of a prescription approval code, wherein the prescription approval code is generated only upon verifying that the patient is registered in the computer readable storage medium using the 0 patient's unique patient identification number. In a further preferred embodiment, the prescription according to the invention contains the unique patient identification number. In another preferred embodiment, the computer readable storage medium is consulted remotely. 5 The present invention also provides a system for dispensing one or more drugs to a patient in need of the drug(s) so as to minimise the risk of an adverse side effect known or suspected of being caused by the drug(s), wherein one of the drugs is thalidomide; the system comprising: registration of a patient, a prescriber and a pharmacy in a computer readable 20 storage medium; assignment of a unique patient identification number to the patient; recordal in the computer readable storage medium of an assessment that the risk of an adverse side effect occurring in the patient is acceptable; and 9 generation of a prescription approval code associated with each presentation by the patient of a prescription to the pharmacy for dispensing, after consultation of a computer readable storage medium that confirms that: the patient, prescriber and pharmacy are registered in the medium; and 5 the risk of an adverse side effect occurring is acceptable. The methods described herein provide advantageous and effective means for monitoring, controlling and authorizing the distribution to patients of drugs known or suspected of causing adverse side effects (e.g. thalidomide). The methods of the present invention include a variety of checks and balances which serve to limit 10 unauthorized and possibly inappropriate distribution of the drug. These methods are particularly applicable to distribution of teratogenic drugs, in which case the checks and balances may be particularly advantageous for preventing distribution of the drug to patients whose use of the drug may pose an unacceptable risk that a foetus carried by the patient or a recipient of the bodily fluids of the patient will be exposed to such drugs. 15 Accordingly, the present methods may be advantageously used to avoid exposure of foetuses to teratogenic drugs, thereby avoiding the terrible birth defects which may result from such exposure. As used herein, except where the context requires otherwise, the term "comprise" and variations of the term, such as "comprising", "comprises" and "comprised", are not 20 intended to exclude further additives, components, integers or steps. It will be understood that the invention disclosed and defined in this specification extends to all alternative combinations of two or more of the individual features mentioned or evident from the text or drawings. All of these different combinations constitute various alternative aspects of the invention. 25 Various modifications of the invention, in addition to those described herein, will be apparent to those skilled in the art from the foregoing description. Such modifications are also intended to fall within the scope of the appended claims.

10 Brief description of the drawings Figure 1 is an example of a consent form that is completed by a patient and prescriber as part of the patient's registration process. Detailed description of the embodiments 5 The present invention is directed generally to methods for the delivery of drugs known or suspected of causing an adverse side effect, especially teratogenic drugs, to patients. The present invention is particularly concerned with reducing the risk of an adverse side effect known or suspected to be caused by a drug occurring in a patient. That is, 10 reducing or minimizing the possibility that a contraindicated individual will be exposed to the potentially hazardous drugs. As used herein, the term "contraindicated" refers to any condition in a patient which renders a particular line of treatment, including the administration of one or more drugs, undesirable or improper. This condition may be preexisting, or may develop while the patient is taking the drugs, 15 including conditions which may result directly or indirectly from treatment with the drugs. Thus, contraindicated drugs include, for example, teratogenic drugs whose administration, for example, to pregnant patients is importantly avoided due to the risks to the foetus. Drugs may also be considered "contraindicated," as the term is used herein, if use of a drug by patients who are also taking another drug is known or 20 suspected of producing an adverse side effect in those patients, or in a foetus carried by such patients. The term "drug", as used herein, refers to any substance which is intended for use in the diagnosis, cure, mitigation, treatment or prevention of disease, or to affect the structure or function of the body. A teratogenic drug, as the term is used herein, is a 25 drug that is known or suspected of causing birth defects if taken by a pregnant woman. More specifically, it is a drug that is known or suspected of affecting, in a detrimental way, the development of the foetus. In particular, the drugs relevant to this invention are thalidomide and lenalidomide.

11 The term "adverse side effect" refers to any abnormality, defect, mutation, lesion, degeneration or injury which may be caused by taking the drug. The side effect may be one which is likely to arise in the patient or in a foetus carried by the patient. The side effect may also be one which is likely to arise in a recipient of the bodily fluid of the 5 patient, or foetus carried by such recipient. Preferably, the patient is a female of childbearing potential. That is, a female who is capable of becoming pregnant. The drug may be received by a female of child bearing potential either directly or indirectly. A direct route by which the drug may be received includes, for example, 0 ingestion of the drug. An indirect route by which the drug may be received includes, for example, through receipt of body fluids from a person taking the drug. The method of the present invention involves the generation of a prescription approval code upon the presentation by a patient to a pharmacy of a prescription for the drug to be dispensed. 5 In certain embodiments of the invention, the methods may require that the registered pharmacy communicates directly or indirectly with a computer readable storage medium for the generation of a prescription approval code in respect of each dispensing of the drug to the patient. The registration of the pharmacy is discussed in detail below. This approval code is preferably not provided unless the prescriber, the pharmacy, the 20 patient, the patient's risk group and the patient's informed consent have been properly registered in the storage medium, as discussed in more detail below. As used herein, the term "prescriber" refers to any individual who is capable of prescribing drugs, including, for example, a medical doctor. Thus, to comply with the present methods and receive approval to dispense the drug as 25 prescribed, the registered pharmacy need only obtain the prescription approval code. In this manner, the effort required by the pharmacy is minimized, and greater compliance with the present methods may efficiently and advantageously be achieved. Additionally, 12 the embodiments described herein provide greater assurance that all required further information has been obtained before the drug is dispensed to the patient, and thereby minimize the risk that an adverse side effect will occur. In practice, if the preconditions to filling a prescription are not met (e.g. informed 5 consent has not been registered), the prescription approval code will not be generated. The pharmacy and/or the Risk Management Center (RMC) may thereby be alerted to a potential breakdown of the risk management method and take appropriate action. As used herein, the term "Risk Management Center" or "RMC" refers to a centralised collection of information that manages the risk of adverse side effects known or 10 suspected of being caused by the drug occurring. The collected information may include, for example, specific details about patients (e.g. age, sex, contact details, and the like), information about the drug (e.g. new side effects, contraindications, and the like) and the preconditions that need to be satisfied before the prescription approval code is generated (e.g. informed consent, and the like). The information may be stored 15 by the RMC in forms that will be apparent to a person of ordinary skill in the art (e.g. a database). In a preferred embodiment, the information is stored in a computer readable storage medium. Typically, the provider or distributor of the drug is closely connected with the RMC. The RMC may be a department of the organisational structure of the distributor. 20 In certain embodiments of the present invention, the prescription approval code is only generated upon the pharmacy confirming that the patient has been provided with information about the drug. Typically, the pharmacy would provide the patient with the information. However, this does not preclude the patient from receiving the information in another way e.g. from the prescriber. 25 In another embodiment, the prescription approval code is generated after it is also confirmed that the patient is not pregnant. The confirmation may be made by the pharmacist identifying a negative result of a pregnancy test.

13 In another embodiment, when the patient is a female of childbearing potential, the prescription approval code is issued before the prescription is dispensed. According to the present invention, the prescription approval code is generated only after it is verified that the patient is registered in a computer readable storage medium. 5 Suitable computer readable storage media which may be employed for registration of the patients (as well as the prescribers and pharmacies, as discussed below) will be apparent to one of ordinary skill in the art, once armed with the teachings of the present application. The computer storage medium may be accessed in ways that will be apparent to a 0 person of ordinary skill in the art. For example, the computer readable storage medium may be accessed directly using an application adapted to generate queries and/or write data to the computer readable storage medium. If the computer readable storage medium is remotely located, access may be provided via a client application such as a web browser or other client side application e.g. a dedicated application for reading and 5 writing to the computer readable storage medium. The computer readable storage medium may be associated with a web browser adapted to dynamically generate web pages in response to requests received from a client side application. In order to become registered in the computer readable storage medium, the patient may be required to comply with various aspects of the methods described herein. The 20 registration of the patient may be carried out by a registered pharmacy, for example at the time of the patient's initial visit to the pharmacy. It has been found, however, that it may be more efficient, and better compliance with the methods of the present invention may be provided, if registration of the patient is carried out by a registered prescriber of the drug at the time the initial prescription is generated. 25 According to the present invention, once the patient is registered in a computer readable storage medium, as discussed above, the patient will be assigned a unique patient identification number (UPIN). A unique patient identification number means that no two patients are assigned the same number. In addition, a patient's UPIN will remain the same for as long as the patient is registered in the computer readable storage 14 medium. The number may be made up of, for example, one or more letters, numbers, symbols, and the like, or a combination of any of these. In one preferred embodiment, the UPIN is included on a script by the prescriber, along with details of the prescriber and any relevant test results (e.g. pregnancy test results). 5 In preferred form, the prescriber will typically have a registration card or form filled out for the patient, which includes information on the patient, such as the patient's name, sex, mailing address, date of birth, and the like. Information on the prescriber and dispensing pharmacy, such as the information described below for the registration thereof, may also be desirably entered on the patient registration card or form. The 10 completed card or form may then be forwarded to the manufacturer or distributor of the drug, or other authorized recipient of the registration form, for example, by mail, facsimile transmission or on-line transmission. Where registration is by mail or facsimile, entry of the registration into the computer readable storage medium may preferably include the use of optical character recognition (OCR) software. It is also possible that 15 the registration of the patient into the computer readable storage medium may also be achieved, for example, by telephone and/or through the use of an integrated voice response system. Preferably, information will also be collected from the patient that may be probative of the risk that a known or suspected side effect will occur if the drug is taken by the 20 patient. The type of information that is gathered from the patient will depend on the preconditions that need to be fulfilled before a prescription approval code is issued. The preconditions themselves may vary over time based on new information that becomes available about the drug (for example, new side effects, contraindications, and the like). Preferably, the new information is entered into a computer readable storage medium, 25 which allows the preconditions to be altered in accordance with the new information. In this way, the relevance of the preconditions can be maintained and centrally implemented, which will lead to an increase in the accuracy, efficiency and safety of the risk assessment process. The information gathered from the patient may also be compared with a predefined set 30 of risk parameters for the drug, which in turn define a plurality of risk groups, so that 15 analysis of the information will permit assignment of the patient to at least one of the risk groups. The preconditions discussed above may also correlate with the risk groups. Preferably, this risk group assignment is then also entered into the computer readable storage medium. This assignment may be performed by the prescriber, who may then 5 include the risk group assignment on the patient's registration card or form, or may be performed by another individual, such as a nurse, technician, or office personnel, who preferably interprets the information and assigns the patient to one of the risk groups, accordingly. An example of a risk group that may be established is one that includes patients to whom administration of the drug is strictly contraindicated. By assigning each 10 patient to a risk group, the steps that will be taken to minimize the chance that the drug is dispensed to a contraindicated patient, and to minimize the risk that a known or suspected adverse side effect will occur, can be tailored to suit the circumstances of that particular patient. As discussed above, it is preferable that a plurality of risk groups, each based upon a 15 predefined set of risk parameters, be established for the drug which is to be administered. As will be evident to those skilled in the art, the risk parameters to be considered and the risk groups defined by those parameters will be based upon factors which influence the risk that a known or suspected adverse side effect will occur if a patient receives the drug, and will vary depending upon the drug in question. Where the 20 drug is a teratogenic drug, for example, such risk parameters may include elements which would impact the risk of a foetus and/or a female of child bearing potential being exposed to the drug, such as the age, sex and reproductive status of the patient. For example, a first risk group may comprise female patients of child bearing potential; a second risk group may comprise female patients of non-child bearing potential; a third 25 risk group may comprise sexually active male patients; and a fourth risk group may comprise sexually inactive male patients. Preferably, the risk group is female patients of child bearing potential. It is preferred that for any given risk group, there may be defined a predetermined additional set of information which is to be collected from the patient.

16 This additional set of information may be obtained prior to the initial dispensing of the drug to the patient and/or may be obtained from the patient on a periodic basis. This information may include information not previously obtained from the patient, or may simply reiterate previously asked questions, and repeat diagnostic tests which were 5 conducted previously. The information may relate to the patient's conduct, or may relate to the patient's past or ongoing medical treatment, such as other procedures or medication which the patient may have received or is still receiving. For example, the additional set of information may be in the form of an interview with a doctor, a survey or questionnaire regarding the patient's behavior and compliance with risk avoidance 10 measures and may thus be probative of whether the risk of occurrence of an adverse side effect has increased, decreased or remained the same. Based upon the responses by the patient, the patient's risk group assignment may, if appropriate, be changed accordingly. The additional information may also include the results of certain diagnostic tests which 15 have been performed on the patient. Such diagnostic tests may be probative, for example, of the risk of exposure of a foetus to a teratogenic drug, may test for the presence of a risk factor for the adverse side effect of concern, or may be probative of the onset of that side effect. Where the use of combinations of more than one drug are known or suspected of causing an increased risk of the occurrence of a side effect, the 20 diagnostic testing may include testing for the presence of one or more of those drugs, or evidence of the use by the patient of such other drugs. Additionally, diagnostic tests may be probative of the concentration of one or more drugs, including the prescribed drug or drugs, to assure that appropriate dosing is maintained. Such diagnostic testing may be conducted on any bodily fluid or waste product of the 25 patient, including the blood, serum, plasma, saliva, semen or urine, as well as the faeces. Diagnostic testing may also be performed on a biopsy of any tissue of the patient or may include genetic testing, which may be indicative of a genetic predisposition to a particular adverse side effect. Other forms of diagnostic testing, such as diagnostic imaging, or tests which may be probative of the proper functioning of any 30 tissue, organ or system are also contemplated. Preferably, the additional information and/or diagnostic test results are obtained and entered in the computer readable 17 storage medium before the patient is approved to receive the drug. Additionally, where the information indicates that the risk of the adverse side effect occurring outweighs the potential benefit of the drug, the patient may be assigned to a risk group that will preclude approval of dispensation of the drug to that patient. 5 In the course of an examination of a patient, including patients suffering from one or more diseases and/or disorders such as, for example, ENL or multiple myeloma the prescriber may determine that the patient's condition would be improved by the administration of a drug such as, for example, a teratogenic drug, including thalidomide. Prior to prescribing the drug, the prescriber preferably counsels the patient, for example, 0 on the various risks and benefits associated with the drug. For example, the prescriber preferably discusses the benefits associated with taking the drug, while also advising the patient on the various side effects associated therewith. In embodiments of the invention wherein the prescriber assigns the patient to a specific risk group, the disclosure is preferably tailored to that risk group assignment. Thus, a patient who may 15 acquire a condition for which the drug is contraindicated is preferably counseled by the prescriber on the dangers associated therewith and advised as to risk avoidance measures which may be instituted. Preferably the patient is provided full disclosure of all the known and suspected risks associated with taking the drug. For example, in the case of teratogenic drugs, the 20 prescriber preferably counsels the patient on the dangers of exposing a foetus, either one which may be carried by the patient or one carried by a recipient of the bodily fluids of the patient, to the teratogenic drug. Such counsel may be provided verbally, as well as in written form. In preferred embodiments, the prescriber and/or pharmacist provides the patient with literature materials on the drug for which a prescription is contemplated, 25 such as product information, educational brochures, continuing education monographs, and the like. Thus, in the case of methods involving teratogenic drugs, the prescriber and/or pharmacist preferably provides patients with literature information, for example, in the form of the aforesaid product information, educational brochures, continuing education monographs, and the like, warning the patient of the effects of the drug on 30 foetuses. In the case of other drugs which are known or suspected of causing an adverse side effect, the patient is counseled as to the dangers of taking the drugs, and 18 of steps which may be taken to avoid those risks. For example, if the concomitant use of the drug and another drug, for example alcohol, is to be avoided, the prescriber and/or pharmacist advises the patient of the risks of drinking alcohol while taking the drug. With particular reference to counselling provided in connection with teratogenic drugs, 5 the prescriber preferably counsels female patients that such drugs must never be used by pregnant women. If the patient is a female of child-bearing potential (i. e., a female who is capable of becoming pregnant), the prescriber preferably counsels the patient that even a single dosage of certain teratogenic drugs, such as thalidomide, may cause birth defects. Accordingly, the patient is preferably counseled to avoid sexual 0 intercourse entirely, or if sexually active, to use appropriate forms of contraception or birth control. For both male and female patients, the prescriber preferably provides counsel on the importance of using at least two forms of effective birth control methods, with one form preferably being a highly effective hormonal method, and the other form preferably being an effective barrier method. The patients are preferably counseled to 5 use the birth control methods for a period of time prior to and during treatment with the teratogenic drug, as well as for a period of time after treatment with the drug has been terminated. In preferred embodiments, the patient is counseled to use at least two forms of birth control for at least about 4 weeks prior to initiation of treatment, during treatment, and for at least about 4 weeks after treatment has been terminated. It may be 20 desirable for the prescriber to personally provide female patients who are capable of becoming pregnant with one or more contraceptive devices or formulations. Male patients who are being prescribed a teratogenic drug are preferably counseled to use condoms every time they engage in sexual relations, since many teratogenic drugs may be found in semen. Male patients are also preferably counseled to contact their 25 prescriber if they have sexual intercourse without a condom, and/or if it is believed that they may have caused a pregnancy. As with female patients, it may be desirable for the prescriber to provide male patients who are capable of impregnating female patients with a contraceptive device or formulation. Other advice relative to birth control that the prescriber may provide to the patient would be apparent to one skilled in the art, once 30 armed with the teachings of the present application. If the prescriber who is prescribing the teratogenic drug is unaware of certain aspects of the available forms of birth control 19 and the advantages and disadvantages associated therewith, the patient should be referred to a prescriber who is knowledgeable on such matters, prior to being prescribed the involved drug. Counselling on teratogenicity, birth control, and the like is preferably given only to female patients who are capable of becoming pregnant, or to male 5 patients who are capable of having sexual relations with partners who are or can become pregnant. In this manner, unnecessary counselling, for example, to women who are no longer of child-bearing age or men who are incapable of sexual relations with such women, may be avoided. With further reference to methods involving teratogenic drugs, it is also preferred that 0 the prescriber advise the patient to not share the drug with anyone else, and particularly that the drug should be kept out of the reach of children as well as women of child bearing potential. In the case of female patients, particularly female patients of child bearing potential, the prescriber should give the patient a pregnancy test, preferably a serum pregnancy test, prior to and during treatment with the teratogenic drug. To begin 5 receiving the teratogenic drug and to continue taking the drug, female patients of child bearing potential should continue to have negative pregnancy tests. The patient is also preferably counseled by the prescriber to discard or return to the prescriber, pharmacy, manufacturer or distributor any unused portion of the prescribed drug. As would be apparent to one of ordinary skill in the art, once armed with the teachings 20 of the present application, one or more aspects of the counselling described above may be applicable, in certain circumstances, for drugs other than teratogenic drugs. In addition to receiving counselling on the drug being prescribed, including counselling, for example, on birth control, and prior to receiving a prescription for the drug, the methods of the present invention preferably involve requiring the patient to fill out an 25 informed consent form which is signed by the prescriber, as well as the patient. The prescriber should retain a copy of the informed consent form for his/her records. Verification that the patient has given his/her informed consent may also be registered in the computer readable storage medium and/or forwarded to the manufacturer or 20 distributor of the drug, or other authorized recipient of the registration form, for example, by mail, facsimile transmission or on-line transmission. Where registration is by mail or facsimile, entry of the registration into the computer readable storage medium may preferably include the use of optical character recognition (OCR) software. It is also 5 possible that the registration of the patient into the computer readable storage medium may also be achieved, for example, by telephone and/or through the use of an integrated voice response (IVR) system. Preferably, this verification is provided by the prescriber, and may be included, for example, with the patient registration information and risk group assignment. It has surprisingly been found that by having the prescriber, 10 rather than the pharmacy, verify the patient's informed consent, the methods of the present invention may operate more efficiently, leading to better compliance, and hence decreased risk that the adverse side effect will occur. By filling out and signing an informed consent form, the patient acknowledges that he/she understands the risks associated with taking the drug. In the informed consent 15 form, the patient preferably agrees to comply with the risk avoidance measures provided, and to behave in a manner which is consistent with the prescriber's counsel. These measures may include, for example, in the case of teratogenic drugs: . The patient agreeing to use at least one form of birth control, with female patients agreeing to use at least two forms of birth control; 20 . Female patients agreeing also to undergo pregnancy testing before, during and after treatment with the drug; * Male patients agreeing to avoid having unprotected sexual relations with a woman, particularly a woman of child-bearing potential during treatment with the drug; 25 * Patients agreeing to not share the drug with anyone, and acknowledging that they cannot donate blood while taking the drug; . Male patients agreeing to not donate sperm while taking the drug.

21 In addition, the patients will preferably agree to take part in a confidential patient survey and/or interview with a doctor, for example, before, during and after treatment with the drug. In this manner, the survey and interview may assist in identifying patients who engage in risky behavior, as well as patients who are non-compliant with the methods 5 described herein. The information obtained from the survey and/or interview is preferably also entered into the computer readable storage medium. Once entered into the computer readable storage medium, the prescriber, manufacturer and/or distributor of the drug may be able to glean therefrom information regarding the level of risk associated with the 10 administration of the involved drug to the various patients. Accordingly, it may be possible to identify, from among the entire population of registered patients, one or more subpopulations of patients for which the involved drug may be more likely to be contraindicated. In preferred embodiments, female patients will agree to complete some form of patient 15 survey and/or attend an interview as required, with male patients agreeing to complete a patient survey and/or attend an interview at least once every three to six months. The survey and/or interview may be conducted by mail, facsimile transmission, on-line transmission or by telephone. Preferably, the survey and/or interview is conducted by telephone through the use of an IVR system. This information will allow updating of the 20 preconditions that need to be fulfilled before a prescription approval code is issued. Such surveys may be very brief and limited to one or two questions, or may be much more detailed. After the patient has received counselling as described above, has filled out and signed an informed consent form, and it is determined that the drug which is to be prescribed is 25 not contraindicated for the patient (such as, for example, a negative pregnancy test in the case of female patients for whom a prescription is desired for a teratogenic drug), the prescriber may prescribe the drug to the patient. In preferred embodiments of the present invention, the amount of the drug which is prescribed to the patient is for a limited amount, preferably no more than about 28 days. Refills for the drug will not be 22 permitted without a renewal prescription from the prescriber, as discussed in detail below. In a further preferred embodiment, the prescription according to the invention contains the unique patient identification number. 5 In order to have the prescription filled, the patient preferably presents the prescription to a pharmacy that has been registered, as discussed in detail below. It is contemplated that the patient may bring the prescription to an unregistered pharmacy. If so, the pharmacy may take steps to become registered, for example, by immediately contacting the manufacturer of the drug. Once registration of the pharmacy is completed, the 0 distribution procedure described herein may resume, per the discussion hereinafter. Of course, this may introduce a delay into the prescription process, and the patient may desire to take the prescription for the drug to an alternate, registered pharmacy. If verification of such informed consent has not previously been registered in the computer readable storage medium, the prescription may not be filled. In this case, the pharmacy 5 may contact the prescriber to have an informed consent form filled out for the patient. As noted above, the drug is preferably prescribed and dispensed to the patient in a limited amount, with a prescription amount of no more than about 28 days being preferred, and preferably with no refills being permitted. Thus, for the patient to obtain an additional prescription, it is generally necessary for the patient to have a follow-up 20 visit with the prescriber. Such a follow-up visit preferably takes place at least each time the patient requires a renewal of the prescription, and possibly more often if the patient requires, for example, additional counselling. At the follow-up visit, the patient will preferably receive additional counselling regarding the risks and benefits associated with taking the drug, as well as further counselling on birth control (if applicable). In one 25 form of the invention, the patient also completes an additional patient survey and/or attends an interview with a doctor to provide current information regarding their lifestyle, including their sexual behavior and, if the patient is a female of childbearing potential, be administered a new pregnancy test. After receiving the counselling and completing the patient survey, and if the pregnancy tests for female patients are negative, the 30 prescriber may fill out a new prescription for the drug. As with the original prescription, 23 the renewal prescription is preferably for a limited period of time, with no more than about 28 days being more preferred. Preferably, the prescriber and the pharmacy are also registered in one or more appropriate computer readable storage media, as described in more detail below, as a 5 prelude to the registration of the patient. If the prescriber is not registered in the computer readable storage medium, the prescriber will be ineligible to prescribe the drug. Similarly, if the pharmacy is not registered in the computer readable storage medium, the pharmacy will be ineligible to dispense the drug. The computer readable storage medium in which the prescriber is registered may be 10 the same as, or different from, the computer readable storage medium in which the patients are registered. Once registered in the computer readable storage medium, the prescriber may be eligible to prescribe the drug to patients in need of the drug. Generally speaking, in order to become registered in the computer readable storage medium, the prescriber may be required to comply with various aspects of the methods 15 described herein including, for example, providing patient education and counselling, and the like, as described in detail above. The registration of the prescriber in the computer readable storage medium may be achieved by providing the prescriber, for example, by mail, facsimile transmission, or on-line transmission, with a registration card or form, preferably together with appropriate educational materials concerning, for 20 example, the particular drug for which the prescriber is being registered to prescribe, as well as suitable methods for delivering the drug to the patient, including the drug delivery methods described herein. The prescriber will preferably complete the registration card or form by providing information requested therein, and the registration card or form will preferably be returned to the manufacturer or distributor of the drug, or 25 other authorized recipient of the registration materials, for example, by mail, facsimile transmission or on-line transmission. Information which may be requested of the prescriber in the registration card or form may include, for example, the prescriber's name, address, and affiliation, if any, with one or more health care institutions. The prescriber's information in the registration card or form is then entered into the computer 30 readable storage medium. It is contemplated that the registration of the prescriber into 24 the computer readable storage medium may also be achieved, for example, by telephone, and/or through the use of an IVR system. The computer readable storage medium in which the pharmacies are registered may be the same as, or different from, the computer readable storage medium in which the 5 prescribers and/or patients are registered. Once registered in the computer readable storage medium, the pharmacies may be eligible to dispense the involved drug to patients who are in need of the drug. Generally speaking, in order to become registered in the computer readable storage medium, the pharmacy may be required to comply with various aspects of the methods described herein including, for example, registering 0 the patient (preferably also in a computer readable storage medium), ensuring that the patient complies with certain aspects of the drug delivery methods, as well as other aspects of the present methods, as described in detail below. As with the registration of the prescriber in the computer readable storage medium, the registration of the pharmacy may be achieved by providing the pharmacy, for example, by mail, facsimile 15 transmission, or on-line transmission, with a registration card or form, preferably together with appropriate educational materials concerning, for example, the particular drug for which the pharmacy is being registered to dispense, as well as suitable methods for delivering the drug to the patient, including the drug delivery methods described herein. The pharmacy may then have the registration card or form completed 20 by providing the information requested therein, which thereafter may be returned to the manufacturer or distributor of the drug, or other authorized recipient of the registration card or form, for example, by mail, facsimile transmission or on-line transmission. Information which may be requested of the pharmacy in the registration card or form may include, for example, the pharmacy's name, address, and affiliation, if any, with any 25 health care institution such as, for example, a hospital, health care organization, and the like. The pharmacy's information in the registration card or form is then preferably entered into the computer readable storage medium. It is contemplated that the registration of the pharmacy into the computer readable storage medium may also be achieved, for example, by telephone and/or through the use of an integrated voice 30 response system.

25 The drug is preferably supplied to the pharmacy (as well as the patient) in packaging, such as individual blister packs, which includes warnings regarding the risks associated with the drug, as well as the importance of various aspects of the present methods such as, for example, pregnancy testing and the use of contraception (in the case of 5 teratogenic drugs), and the dangers associated with sharing the drug with others, among other aspects. In certain embodiments, the prescriber may also receive reminders, for example, via mail, facsimile, or on-line transmission, from the manufacturer, distributor or other group or body providing oversight on drug distribution, that the prescriber has prescribed a 10 hazardous drug to patients which may be contraindicated, and that the involved patients may require additional counselling and diagnostic testing. Such reminders may preferably be delivered to the prescriber, for example, from about 14 to about 21 days after the previous prescription was filled. In respect of each filling out of a prescription (i.e. dispensing the drug), the pharmacy 15 preferably confirms, for example, by accessing a computer readable storage medium that the patient has been registered and is eligible to receive the drug. The computer readable storage medium may be accessed using an application adapted to generate queries and/or write data to the computer readable storage medium. If the computer readable storage medium is remotely located, access may be provided via a client 20 application such as a web browser or other client side application e.g. a dedicated application for reading and writing to the computer readable storage medium. The computer readable storage medium may be associated with a web browser adapted to dynamically generate web pages in response to requests received from a client side application. 25 When patient eligibility has been confirmed, the pharmacy may dispense the drug to the patient. If the patient is ineligible, the pharmacy generally may not dispense the drug to the patient. The pharmacy may then contact, for example, the prescribing prescriber or the manufacturer of the drug to initiate patient registration.

26 In preferred form, the pharmacy will be precluded from dispensing the drug if the patient has more than about 7 days of drug supply from the previous prescription, and/or if the new prescription was written more than about 14 days before the date the patient visits the pharmacy to have it filled. 5 The registration into one or more computer readable storage media of the prescriber, pharmacy and patient, according to the methods described herein, provide a means to monitor and authorize distribution of contraindicated drugs, including teratogenic drugs. Thus, the computer readable storage media may serve to deny access to, dispensing of, or prescriptions for contraindicated drugs, including teratogenic drugs, to patients, 10 pharmacies or prescribers who fail to abide by the methods of the present invention. As noted above, prescribers who are not registered in a computer readable storage medium generally may not prescribe the drug, and pharmacies who are not registered generally may not dispense the drug. Similarly, the drugs generally may not be prescribed and/or dispensed to patients who are not registered in a computer readable 15 storage medium. In addition, patients may be required to present an informed consent form to the pharmacy. Unless such a form is presented to the pharmacy, or verification of such informed consent has been provided by the prescriber and registered in the computer readable media (e.g. a UPIN), the patient generally may not receive the prescription for the drug. As noted above, only limited amounts of the drug may be 20 prescribed to the patient, with no refill prescriptions being permitted. Example The invention will now be described with reference to the following non-limiting example. It should be understood that the description following is illustrative only and should not be taken in any way as a restriction on the generality of the invention 25 described above. The following is an example of one embodiment of the present invention. As an initial step, the prescriber seeks to register a new patient. The prescriber themselves must also be registered before he/she is able to register a new patient.

27 The registration process requires that the patient complete a consent form, as shown in Figure 1. The form requires the patient to provide information such as their age and sex, and to state that he/she has been made aware of the risks associated with thalidomide. At this stage, counselling (as discussed further below) is also offered or required. If the 5 patient is a female of child bearing potential (FOCBP), she is required to state on the consent form that she is not and will not become pregnant, both while taking thalidomide and up to four weeks after she has ceased treatment with thalidomide. FOCBPs must also state that they will rely on a highly effective form of birth control (e.g. Intra Uterine Devices (IUDs), hormonal methods such as birth control pills, patches, 0 injections and implants, tubal ligation or partner's vasectomy) at all times during the treatment and undergo periodic pregnancy tests. If the patient is a male, he is required to state that he will use a barrier form of contraception (e.g. condoms) during the treatment and also up to four weeks after ceasing the treatment, particularly if he has sexual intercourse with a FOCBP. 15 The patient must also state that he/she will not donate blood during treatment and up to four weeks after ceasing treatment, and that he/she will not share their drug with anyone. Nor will a male patient donate sperm. The prescriber is also required to complete the consent form by providing information including whether the patient is a FOCBP and whether the patient has undergone any 20 other forms of therapy. The prescriber also has to state on the consent form that they have explained the risks associated with taking thalidomide to the patient. Once the initial consultation process and the consent forms have been completed, the prescriber forwards the completed consent forms to a RMC. The RMC enters the information provided by the prescriber into a computer readable storage medium. A 25 UPIN is then assigned to the patient and provided to the prescriber. Once the patient is assigned a UPIN, he/she may undergo counselling (if they haven't already done so during the initial consultation, as mentioned above). The aim of the counselling is to make the patient aware of the teratogenic risk associated with 28 thalidomide and the need to use appropriate contraception methods. If the patient is a FOCBP, the prescriber requires that the patient undergoes a pregnancy test before the patient can receive a prescription. The pregnancy test may be conducted at the time of the consultation or in the three days prior to the visit. If the result obtained is positive 5 (i.e. the patient is pregnant) the patient is taken off the program and no thalidomide treatment is provided to the patient. If the result is negative, thalidomide can be prescribed to the patient. The prescriber will then write a prescription for thalidomide and give it to the patient. The prescriber is required to ensure that the patient's UPIN appears on the prescription. 10 The prescription also contains the usual information such as the prescriber's details (including registration numbers) and the result of the pregnancy test (if the patient is a FOCBP). The patient is then directed to a registered pharmacy. The registered pharmacy has received, from the RMC, details of the type of information it needs to collect from the 15 patient for forwarding to the RMC, in order for a prescription approval code to be generated. Details that need to be provided include the pharmacy, the patient's UPIN and prescriber details, the dose prescribed, whether counselling was offered to the patient and the date and result of the pregnancy test (if applicable). The information is then forwarded to the RMC, where it is verified. The verification 20 process includes checking that the patient has been registered and that he/she does not fall into any risk groups for which thalidomide is contraindicated. Once the script is verified by the RMC a prescription approval code is assigned to the prescription by the RMC. The prescription approval code is then provided to the pharmacist, who may then dispense thalidomide to the patient. 25 If a prescription approval code is not provided to the pharmacist, the pharmacist will notify the patient and/or prescriber.

Claims (5)

1. A method of treating a patient with thalidomide by permitting a prescription for thalidomide to be filled by a pharmacy only after a prescription approval code has been communicated to the pharmacy to authorise the dispensing of thalidomide to the 5 patient, comprising the steps of: upon presentation by the patient of the prescription to the pharmacy, consulting a computer readable storage medium in which the patient, a prescriber and the pharmacy are registered, each patient having a unique patient identification number assigned to the patient, and in which is recorded an assessment of whether the risk of an adverse l0 side effect occurring in the patient is acceptable; generating a prescription approval code associated with the presentation by the patient of the prescription for thalidomide upon verifying that: the patient, prescriber and pharmacy are registered in the medium; and the risk of an adverse side effect occurring in the patient for this 15 presentation is acceptable; and communicating the prescription approval code to the pharmacy.

2. A method according to claim 1, wherein the prescription approval code is generated from a list stored in the computer readable storage medium.

3. A method according to claim 1 or claim 2, wherein the prescription approval code 20 is generated after it is also verified that the patient is not pregnant.

4. A method according to any one of the preceding claims, wherein, when the patient is a female of childbearing potential, the prescription approval code is issued before the prescription is dispensed. 30

5. A method according to any one of the preceding claims, wherein the method includes the further step of, upon presentation by a patient to a pharmacy of a prescription for lenalidomide to be dispensed, requiring generation of a prescription approval code, wherein the prescription approval code is generated only upon verifying 5 that the patient is registered in the computer readable storage medium using the patient's unique patient identification number.