WO2009063209A1

WO2009063209A1 - Marketing surveillance system and method

Info

Publication number: WO2009063209A1
Application number: PCT/GB2008/003835
Authority: WO
Inventors: Alan Grierson Wade; Gordon Macdonald Crawford
Original assignee: Patients Direct Limited
Priority date: 2007-11-15
Filing date: 2008-11-13
Publication date: 2009-05-22

Abstract

A method for the post marketing evaluation of a drug, in which a drug is given to a person along with an unique identifier which allows access to a drug evaluation system. The person is presented with one or more questions concerning the effect the drug has had on them and the person's responses are analysed to evaluate the drug. The present invention provides for direct communication between the person taking a drug and those undertaking post marketing evaluation without the involvement of a physician. Furthermore the evaluation may be initiated by the patient who may choose to access the drug evaluation system.

Description

Marketing Surveillance System and Method

The present invention relates to a marketing surveillance system and method and in particular to a system and method for the evaluation of drugs after they have been made available for public use.

Drugs are currently launched onto the market following the completion of clinical trials designed to fulfil the regulatory requirements of the licensing authorities. These trials are conducted typically on a patient population of 3000 - 10000 and the patients involved must satisfy stringent eligibility criteria. Patient groups such as the young, the elderly, pregnant or lactating females, and patients with underlying medical conditions or those on concomitant medications are frequently excluded. In addition ethnic groups are often not well represented in clinical trials. With patient populations of about 3000 in clinical trials, the only adverse drug reactions (ADRs) that are likely to have been excluded are those that occur more frequently than 1 in 1000. Since many millions of patients may be exposed to a new drug within months of its launch, it is essential to conduct post marketing surveillance in order to identify serious and uncommon events as well as serious but otherwise common events as soon as possible after the launch of the drug. In the United States in recent years, there have been a number of reports in which drugs and dietary supplements have been linked to serious health problems, which outweigh their potential benefits. According to a report in the Journal of the American Medical Association, adverse drug reactions resulting from correctly administered prescription drugs approved by the FDA (Food and Drug Administration) are responsible for over 100,000 deaths per year in the United States. There are also typically over 2.2 million annual occurrences of non-fatal but serious reactions and millions of complications and disabilities related to the unexpected effects of drugs and a variety of products, many of which remain unreported.

Since the thalidomide disaster in 1964 when almost 10,000 babies were born deformed in the countries where the drug was in common use, several hundred drugs have been withdrawn from the market of their licence and/or modified due to safety issues despite diligent scientific studies being performed before release to the market. It is well recognised that: o our understanding of a drug increases the longer and more widely it is used; o it is only through postmarketing evaluation (PME) following general release of a drug that a full assessment of rare (less than 1 in 5000) serious adverse events and common but less severe events can be detected; o general tolerability in routine use can only be assessed following marketing; o some groups are not well represented in trials; and o the switch of some drugs to OTC classification potentially exposes a completely different group of patients who are more difficult to define than those previously treated by prescription. No structured PME system is yet in place for this group.

In the US, the MedWatch programme allows healthcare professionals and consumers to voluntarily report serious problems that they suspect are associated with the drugs and medical devices that they prescribe, dispense or use.

Reporting can be done online, by phone or by submitting a form. The agency evaluates each report to determine how serious the problem is and may request additional information from the individual who filed the report before taking action. This scheme is very similar to the Yellow card Scheme in the UK. Up to 2007, over 250,000 side effects linked to prescription drugs including injuries and deaths are reported via Medwatch per annum. At the present time, Medwatch is focused exclusively on major safety considerations. In the US, the Food and Drug Administration (FDA) require that 'Physicians should report when there is a suspicion that the drug or device may be related to a serious adverse effect; they are not expected to establish the connection or even wait until evidence seems compelling. "

In the UK there are a number of methods used for the collection of postmarketing safety data. All are aimed at safety and the recordal of serious events with significant consequences. These methods are described below. The Yellow Card Scheme was set up in 1964 (after the thalidomide disaster) and provides the primary means of reporting safety concerns/adverse drug effects (ADE) of licensed medicines. Reports of suspected ADEs are received by the Committee on Safety of Medicines (CSM) of the Medicines and Healthcare Products Regulatory Agency (MHRA) directly from doctors, dentists, coroners, pharmacists and indirectly through pharmaceutical companies.

The results are added to a specialised computer system, Adverse Drug Reactions On-line Information Tracking (ADROIT) to facilitate rapid processing and analysis of reports. The information thus collected is the primary means of monitoring drug safety in normal clinical practice and has over the years provided many important early warnings of new adverse drug reactions. The reports provide evidence which can be used to identify possible risk factors for adverse reactions, such as age, concurrent disease or drug interactions, and whether dose reductions or special warning or precautions require to be issued. On occasions this evidence may result in a drug being withdrawn from the market. However, the Yellow Card Scheme relies on doctors and other health care professionals to voluntarily report incidents which they feel may be related to the medication. For physicians and other professionals this reporting is just one of many tasks and may not be seen as priority.

Despite the fact that ADEs are common, the majority of physicians have never completed a yellow card. In the 40 years since the scheme was set up, less than 500 000 reports have been received. As a result under-reporting is a major and well-documented problem. A recent paper published in the International Journal of Risk and Safety in Medicine and which studied Yellow Card reporting concluded that "the

Yellow Card Scheme is, in important respects, both chaotic and misconceived"

The Drug Safety Research Unit DSRU was set up in 1980 to conduct Prescription Event Monitoring (PEM) in a non- interventional observational cohort technique. It relies on the collection of individual prescriptions after they have been dispensed by pharmacists. The DSRU chooses specific drugs to investigate. It receives copies of all prescriptions dispensed for these drugs in England from the Prescription Pricing Authority. The DSRU then post a questionnaire to the prescribing doctor asking for details of any event that has occurred since the drug was taken. The information is then carefully collated and reported to the relevant authority, the MHRA. This system of post marketing surveillance is slow, (the average time between the drug being dispensed and the dispatch of the green form is six months) and relies on the patient reporting even relatively minor but potentially significant, problems to the doctor. There is good evidence that patients who suffer from a side effect frequently simply stop taking the medicine and either self medicate or await the natural resolution of their symptoms.

Pharmaceutical Company Studies PMS are large studies sponsored by pharmaceutical companies which attempt to monitor the safety of a licensed medicine as it is used in clinical practice. These studies are not non interventional in that, by their very existence doctors are encouraged to prescribe the new drug. In addition there is evidence that these studies have made only a limited contribution to our knowledge of drug safety and suffer from weak design, lack of standardisation and objectivity, and poor patient recruitment.

The feasibility of conducting postmarketing drug surveillance by record linkage has been assessed in Tayside, Scotland (Crombie et al., 1984) and utilised the fact that all hospital discharge data are already computerised by the area health board. The advantage of the system is the relatively low cost and the ability to extend follow-up simply by re-running the computer programmes. However this system can only ascertain adverse effects which are serious enough to require hospitalisation and observed drug-disease associations may de due to confounding factors and are difficult to validate.

In Australia, the system for the postmarket monitoring of adverse reactions is also one of voluntary reporting by health professionals and consumers. Each year the Adverse Drug Reactions Advisory Committee (ADRAC) receives about 12,000 reports. About one-third come from General Practitioners, just under one-third from hospitals, one- quarter from pharmaceutical companies and the remainder from specialists, community pharmacists and consumers. It is recognised that this system is limited by under-reporting and the lack of reliable exposure (usage) data. Furthermore, the information submitted in an adverse reaction report is often incomplete. The contribution from consumers is extremely small.

Most of the European Community (EC) countries have similar systems of voluntary spontaneous reporting of major safety issues to a national body. This reporting is usually only done by health professionals. All suffer from chronic under reporting, incomplete data, and potential filtering by the health professionals.

The central problem with the currently available systems is that of underreporting. Various reasons for underreporting have been put forward the most common of these are:-

• Patients do not report problems to the physician they simply stop taking the drug. This may become an increasingly important factor as more and more asymptomatic conditions are treated as a preventative measure

• Time -physicians are busy and this is just another task not directly related to patient care

• Physicians are inhibited from reporting due to anxieties about legal action if it can be shown that the drug they prescribed has caused harm.

• Physicians filter the information. Even if the patient reports to the physician, the physician may minimise the importance of the symptoms or not attribute the symptom to the drug and hence not make a report.

In Sweden, where reporting is mandatory, it is estimated that 85% of problems are not reported.

It is an object of the present invention to provide a system of post marketing drug evaluation that provides a rapid and accurate assessment of side effects. In accordance with the first aspect of the invention there is provided a method for the post marketing evaluation of a drug, the method the comprising the steps of: providing a drug to a person; providing the person with a unique identifier which allows access to a drug evaluation system, wherein the drug evaluation system once accessed requests the person to provide personal information including contact information to allow the person to be contacted; presenting the person with one or more questions concerning the effect the drug has had on them; and analysing information provided by the person to evaluate the drug.

The present invention provides for direct communication between the person taking a drug and those undertaking post marketing evaluation without the involvement of a physician. Furthermore the evaluation may be initiated by the patient who may choose to access the drug evaluation system.

In the context of the present invention, the term drug means any substance designed to have an effect on the health or wellbeing of a person, including prescription drugs, over the counter dugs, any herbal remedy, health food, "nutriceutical", tonic, potion, ointment or the like.

Preferably, the drug is prescribed by a physician and dispensed by a pharmacist.

Optionally, the drug is a non-prescription drug.

Preferably the unique identifier is provided in combination with information on the drug and the evaluation process. Preferably, the unique identifier is provided separately when the drug is dispensed.

Optionally, the unique identifier is provided in the drug's packaging.

Preferably, the unique identifier is alphanumeric code. Optionally, the unique identifier is a barcode.

Preferably, the drug evaluation system is provided on a secure Internet site.

Optionally, one or more hardcopy questionnaire is provided.

Preferably, the contact information comprises date of birth and/or name and/or address and/or gender.

Preferably, the contact information comprises the person' s e-mail address.

Preferably, the contact information comprises the person's mobile phone number. Preferably, the analysis comprises qualitative analysis of responses provided by the person.

Preferably, the analysis comprises a statistical analysis of the responses provided by the person.

Preferably, the step of presenting the person with one or more question comprises an initial series of questions followed by at least one further set of questions provided to the person after the initial set have been answered. Preferably, the person is contacted and prompted to participate in answering the at least one further set of questions thereby encouraging participation in the post marketing evaluation. Preferably, the contact and prompt is via e-mail.

Preferably, the contact and prompt includes a link to the secure internet site.

Preferably, the link is adapted to access a questionnaire which is associated with the person' s unique identifier such that the person is not required to log on.

Optionally, the contact is via an SMS message or similar message .

Optionally, the contact and prompt asks the person to access their e-mail account to participate further in the post marketing evaluation.

Optionally, the contact and prompt contains one or more questionnaire questions.

In accordance with the second aspect of the invention there is provided a computer system with software loaded thereon which contains program instructions for implementing the drug evaluation system of the method in accordance with the present invention.

The present invention will now be described by way of example only with reference to the accompanying drawings in which: figure 1 is the block diagram of a first embodiment of a method in accordance with the present invention; figure 2 is a block diagram of a second embodiment of a method in accordance with the present invention; figure 3 shows an introductory page of an embodiment of the drug evaluation system in accordance with a third embodiment of the invention; figure 4 shows another page from the embodiment of figure 3 in which the user is asked to enter their personal identification number; figure 5 shows another page from the embodiment of figure 3 in which the user is asked to provide personal details; figure 6 shows another page from the embodiment of figure 3 in which the user is asked to describe symptoms; figure 7 shows another page from the embodiment of figure 3 in which the user is provided with information concerning the evaluation process; figure 8 shows another page from the embodiment of figure 3 in which the user is provided with a final opportunity to amend the information they have given; figure 9 shows another page from the embodiment of figure 3 in which the user is informed about the next stage in the process; figure 10 shows the introductory page of the follow-up questionnaire in accordance with the present invention; figure 11 to figure 14 pages from the questionnaire; figure 15 is a physician consent form; figure 16 provides the user with a final opportunity to amend the information they have given.

An embodiment of the method of the present invention is shown in figure 1. In this embodiment, the method comprises providing a drug to a person, providing a unique identification number 5 to the person once they have decided that they wish to participate in the post marketing evaluation, obtaining information from the person through one or more questionnaire 7 and then analysing the data obtained from the person 9. It will be appreciated that this embodiment provides the basic features of the method employed in the present invention. In this and other embodiments of the present invention the person who participates in the post marketing evaluation does so without the direct input of the physician and provides information by means of the post marketing evaluation system as described herein.

Figure 2 illustrates a more detailed embodiment of the method of the present invention. In this embodiment, a patient visits a physician and is issued with a prescription for a drug 13. The patient then takes the prescription to a dispensing chemist who provides the prescribed drug to the patient 15. At this stage the patient is provided with information concerning the post marketing evaluation of the drug which they have been prescribed and patient is invited to participate in the post marketing evaluation of the drug. If the patient wishes to participate then the information to allow participation is provided along with the prescribed drug by the dispensing chemist. This may be in the form of the leaflet that describes the post marketing evaluation study, provides access to additional information on the study and provides a high unique identification number 17 that allows the patient to participate in the study. In this embodiment of the present invention the unique identification number allows the patient to log on to a secure website where the patient must enter personal details 19. Once this task has been completed one or more questionnaire is sent 21 to the patient and the patient's responses to the questions contained in the questionnaire are analysed 23 as part of the post marketing evaluation of the drug.

Figure 3 to figure 16 describe one embodiment of the present invention in which a post marketing evaluation is conducted using a drug evaluation system which is presented to the patient on one or more secure Internet page. The Internet is a particularly convenient medium for presenting a drug evaluation system because it is widely available and easy to operate. The features of the drug evaluation system could be replicated on another medium such as a cell phone, personal digital assistants (PDA) and or the like. Figure 3 shows the introductory page 25 of the drug evaluation system in accordance with the present invention. The introductory page 25 provides a statement concerning the aims of the evaluation, a link to other information on the company conducting the evaluation 29 and instructions on how to proceed with the evaluation of the particular drug that the patient has been prescribed 31 and 33. The next page 35 (shown in figure 4) provides information on the particular drug 37 which in this example is the flu vaccine along with instructions on how to enter the pin number 39, a field for entering the pin number 41, button 43 for submitting the pin number and links 45 and 47 for obtaining more information.

Figure 5 shows the page of the drug evaluation system in which the patient enters personal details 51. In addition the left hand side of this page 53 provides a step-by-step guide to allow the patient to navigate through the different pages of the system. The page requires the user to enter first name 55, surname 57, gender 59, e-mail address 61, each^' 65, postcode 67 and telephone number 69. In this example of the present invention, the patient is contacted by the evaluator via e-mail. E-mail contact provides a prompt to the use as well as quick and easy access to the system for the patient and as such increases the likelihood that the patient will participate fully in the evaluation. Once this page has been completed the patient moved on to the next page 71. In another embodiment of the present invention, the patient may also be contacted using SMS messages or other forms of electronic data transfer to receive reminders concerning their participation in the evaluation and to allow them to complete the evaluation questionnaire. The system actively prompts participation in the evaluation by contacting the patient periodically and inviting the patient to answer questions concerning their reaction to the drug.

Figure 6 is an example of the type of question that they be asked when conducting an evaluation. In this example 75, the patient is asked questions concerning the level and duration of discomfort after receiving a vaccination. A link to the other information on immunisation 79 is provided and the patient decides to navigate to the next page or the previous page using buttons 83 and 81 respectively.

Figure 7 85 provides information to the patient on how the evaluation process is to continue 87 and asks the patient to confirm 89 that they have read and understood this information. In this example, the evaluator will send one or more e-mails to the patient in order to obtain further information on the vaccine.

Figure 8 shows another field in the drug evaluation system in which the patient is invited to confirm that they wished to finish this stage of the evaluation 97 by clicking the finish button 101. The final part of this stage of the evaluation is shown in figure 9 in which the patient is thanked for registering.

After completing this initial stage of the evaluation process the patient receives an e-mail which provides the patient with a link to the website and invites them to log on to complete another part of the evaluation process. The second part of an evaluation process in accordance with the present invention is illustrated in figures 10 to 16. Figure 10 107 provides a message 109 thanking the patient for logging on and inviting them to enter the details.

Figure 11 111 begins the questionnaire 113. In this embodiment the patient is asked to confirm when they received the flu vaccine and whether they had any side- effects from the vaccine. If the patient answers no to this question then the evaluation process will end. If the patient answers yes, they will be taken to the page shown in figure 12 115 which asks them to describe the side-effects they have experienced 117. Figure 13 asks the patient to describe their response to experiencing the side effect in particular by describing whether they have had the side effect treated. Figure 14 123 contains a message 125 which thanks the patient for their participation and reminds the patient that they will be contacted again in six days. Figure 15 127 is a page 129 describes a situation where the patient has described a possibly significant side-effect of the vaccine. The page contains a doctor's consent form which will allow the evaluator to contact the patient's physician. Figure 16 provides the patient with an opportunity to edit his earlier responses or to finish. The evaluation process may continue thereafter in a similar manner to that described above with the user being prompted to participate via e-mail, SMS messages or the like.

In other embodiments of the present invention, the drug may be an over the counter drug, any herbal remedy, health food, "nutriceutical", tonic, potion, ointment or the like. The evaluation of these drugs can occur in a similar manner to that described above. As these products may be sold without the assistance or advice of a pharmacist, doctor or the like it is anticipated that the unique identifier will be provided in or on the packaging of the product.

By removing the physician from the process of post marketing evaluation and having the patient agree to participate at or before the time the drug has been taken, the present invention has a number of advantages with respect to other types of post marketing evaluation such as: o a more complete and reliable information on safety; o a better early warning of potentially serious adverse events; o more reliable information on tolerability; o a clearer picture of clinical usage; o unbiased/unfiltered by physicians; o Timely ie. be available as soon as possible after the launch of a drug; o Non interventional - collected without unduly influencing the use of the product; o relatively inexpensive to implement; o is applicable to over the counter (OTC) products as well as prescription medicines; and o allows the collection of 'benefit' or efficacy data in a systematic way.

Improvements and modifications may be incorporated herein without deviating from the scope of the invention.

Claims

1. A method for the post marketing evaluation of a drug, the method the comprising the steps of: providing a drug to a person; providing the person with a unique identifier which allows access to a drug evaluation system, wherein the drug evaluation system once accessed requests the person to provide personal information including contact information to allow the person to be contacted; presenting the person with one or more questions concerning the effect the drug has had on them; and analysing information provided by the person to evaluate the drug.

2. A method as claimed in claim 1 wherein, the drug is prescribed by a physician and dispensed by a pharmacist.

3. A method as claimed in claim 1 wherein, the drug is a non-prescription drug.

4. A method as claimed in any preceding claim wherein, the unique identifier is provided in combination with information on the drug and the evaluation process.

5. A method as claimed in claims 1, 2 and 4 wherein, the unique identifier is provided separately when the drug is dispensed.

6. A method as claimed in any preceding claim wherein, the unique identifier is provided in the drug's packaging.

7. A method as claimed in any preceding claim wherein, the unique identifier is alphanumeric code.

8. A method as claimed in any of claims 1 to 6 wherein, the unique identifier is a barcode.

9. A method as claimed in any preceding claim wherein, the drug evaluation system is provided on a secure Internet site .

10. A method as claimed in any preceding claim wherein, one or more hardcopy questionnaire is provided.

11. A method as claimed in any preceding claim wherein, the contact information comprises date of birth and/or name and/or address and/or gender.

12. A method as claimed in claim 11 wherein, the contact information comprises the person's e-mail address.

13. A method as claimed in claim 11 wherein, the contact information comprises the person's mobile phone number.

14. A method as claimed in any preceding claim wherein, the analysis comprises qualitative analysis of responses provided by the person.

15. A method as claimed in any preceding claim wherein, the analysis comprises a statistical analysis of the responses provided by the person.

16. A method as claimed in any preceding claim wherein, the step of presenting the person with one or more question comprises an initial series of questions followed by at least one further set of questions provided to the person after the initial set have been answered.

17. A method as claimed in claim 16 wherein, the person is contacted and prompted to participate in answering the at least one further set of questions thereby encouraging participation in the post marketing evaluation.

18. A method as claimed in claim 17 wherein, the contact and prompt is via e-mail.

19. A method as claimed in claim 17 or 18 wherein, the contact and prompt includes a link to the secure internet site.

20. A method as claimed in claim 19 wherein, the link is adapted to access a questionnaire which is associated with the person' s unique identifier such that the person is not required to log on.

21. A method as claimed in claims 17 to 20 wherein, the contact is via an SMS message or similar message.

22. A method as claimed in claims 17 to 21 wherein, the contact and prompt asks the person to access their e-mail account to participate further in the post marketing evaluation.

23. A method as claimed in claims 17 to 22 wherein, the contact and prompt contains one or more questionnaire questions.

24. A computer system with software loaded thereon which contains program instructions for implementing the drug evaluation system of the method in accordance with the present invention.

25. An item of packaging for packaging a drug, the item of packaging containing a unique identifier for use in the method of the present invention.