A questionnaire-based study was conducted among physicians and members of the general public (hereafter referred to throughout as “patients”) to evaluate attitudes and behavior around use of unlicensed drugs on the NHS. Separate physician and patient questionnaires were devised.

Two hundred and forty-nine (n = 249) medical doctors across a wide variety of medical disciplines took part in online interviews conducted between 3–10 March 2011. The interviews were designed to evaluate prescribers’ attitudes and concerns around use of unlicensed drugs and the influence that various factors may or may not have on prescribing decisions and priorities, as well as assessing the impact of the cost-saving challenges currently being faced by the NHS.

Patient questionnaires were conducted between 4–7 March 2011 and involved completion of an online interview by adults living in the UK (aged ≥18 years, n = 500). The questions asked were designed to assess knowledge of, and concerns around, the use of unlicensed drugs among the general population. Information was also captured around patient–physician interactions in terms of drug prescribing and the degree of trust patients have in their physicians.

To ensure the participating population was representative of the actual population, maximum and minimum quotas were set using the online questionnaire software for key population demographics. For example, once the maximum number of male interviews was met, subsequent questionnaires were only conducted in female participants.

Care was taken to ensure no open-ended questions were asked as part of the questionnaire. The data analysis was based on the numbers captured through the quantitative research. No specific treatments or conditions were mentioned in the course of the interviews. Figures for general population age, sex, and region were weighted where necessary to bring them into line with their actual proportions in the population.

For the purposes of the questionnaire, unlicensed prescribing was defined as “prescribing a treatment for a condition for which it has no license, is administered via a different route and/or where a formulation has been changed”.

An even mix (50/50) of male and female doctors and patients took part in the study, across a wide age range from 18 to ≥55 years (see Tables 1 and 2). 60% of participating physicians worked in secondary care and 40% in primary care; all had prescribing rights.⁶

There was little consensus among physicians on the required evidence base to confirm the safety of a therapy. The majority (62%) believed national or local guidelines to be sufficient proof of safety and 38% of the group felt that recommendation of drugs by their peers was also a sufficient measure.¹¹

The physicians believed the most important consideration when prescribing a therapy was its efficacy data (70%), followed by its safety (25%). Cost and convenience (eg, dosing frequency) were less important considerations.¹² Patients also believed safety and efficacy to be the most important two considerations, but the rank order was reversed with 63% believing safety and 30% efficacy to be the greatest prescribing influences (See Figure 2 and Table 3).¹³

Patient and physician views differed most greatly on the factors that least affect prescribing decisions. Almost two-thirds (64%) of patients believed cost to be the least important factor when prescribing compared with a lower 43% of physicians, suggesting physicians may have a greater awareness than patients of the role cost plays in prescribing decisions (see Table 3).¹²,¹³

Recruitment criteria and sample stratification:

• Physicians (medical doctors) who have prescribing responsibilities – 200 interviews
• General population (age 18+ years) – 500 interviews

Questionnaire length:

• 5-minute questionnaire (generally allows for 10–15 question items)

Method:

• Online (opted-in panels)

Objectives:

• Determine whether physicians are comfortable prescribing unlicensed drugs, what factors determine their prescribing behavior, whether they have concerns about the use of unlicensed drugs, and whether they expect the NHS cost-saving drive to affect their prescribing habits.
• Establish whether the general public have concerns about, or even familiarity with, unlicensed drugs, and their reported interactions with their physician when it comes to prescriptions.

Thank you for participating in this brief survey. This survey is strictly for research purposes, and should take no more than 10 minutes of your time. It is not intended to promote the sale of any product or device, and you will not be contacted for marketing purposes as a result of participating. Your responses will be kept confidential and anonymous, and nothing you say will be attributed to you personally.

We are now being asked to pass on to our client, details of adverse events that are mentioned during the course of market research. Although all your responses will, of course, be treated in confidence and anonymously, should you raise during the interview an adverse event in a specific patient, we will need to report this, even if it has already been reported by you directly to the company or the regulatory authorities using the MHRA’s ‘Yellow Card’ system.

In such a situation, you will be asked whether or not you are willing to waive the confidentiality given to you under the Market Research Code of Conduct specifically in relation to that adverse event. Everything else you mention during the course of the interview will continue to remain confidential, and you will still have the option to remain anonymous if you so wish.

• Are you happy to proceed on this basis?
• Yes – Continue
• No – Thank you and close
• First, some questions to confirm that you qualify for the study:

1. Where do you practice?
   • England..................................................................................................................................... 1
   • Wales ........................................................................................................................................ 2
   • Scotland..................................................................................................................................... 3
   • Northern Ireland......................................................................................................................... 4
   • None of these...................................................................................................... [TERMINATE]
2. Do you currently have prescribing responsibilities?
   • Yes.............................................................................................................................................. 1
   • No........................................................................................................................ [TERMINATE]
3. Are you involved in primary or secondary care?
   • Primary......................................................................................................................................... 1
   • Secondary...................................................................................................................................... 2

In the survey below we will be asking for your opinion on scenarios related to prescribing and the use of unlicensed treatments. When referring to a treatment being unlicensed, we will be using the following definition:

Without a marketing authorization (unlicensed) in the UK for a specific condition or if used with a variation in its licensed formulation or administration.

Throughout this survey, we understand that there are some difficult questions or grey areas. Please answer all questions to the best of your ability.

• 4. Below is a list of factors that you may or may not consider when selecting a treatment to prescribe for a specific condition. In general, how important are each of the following factors when prescribing a treatment? Please rank each of the factors below from 1 to 4, where 1 means it is the most important, 2 is the second most important, and so on. You can only use each number from 1 to 4 once. [RANDOMIZE ORDER OF ITEMS]
  Note: We understand that the factors below are not the only ones to be considered. However, please answer to the best of your ability based on the factors listed below.
  • The proven efficacy of the treatment for that condition ............................................................................ _______
  • The proven safety profile of the treatment for that condition .................................................................... _______
  • The treatment cost ...................................................................................................................................... _______
  • The convenience of the treatment (eg, once daily dosing) ......................................................................... _______
  • Do not agree with any of the above ........................................................................................................................ 9
• 5. When considering the safety of the treatments you might prescribe for a particular condition, with which of the following statements do you agree? (MULTIPLE RESPONSES ACCEPTED)
  • Only a license for use in the specific condition for which I am prescribing treatment provides sufficient evidence of safety ............................................................................................................................................................................ 1
  • A license for use in any condition provides sufficient evidence of safety .................................................................. 2
  • National or local prescribing guidelines (including NICE) provide sufficient evidence of safety, regardless of licensing ....................................................................................................................................................................................... 3
  • Peer recommendation (including in journals) or personal experience provides sufficient evidence of safety, regardless of licensing ................................................................................................................................................................... 4
  • I do not agree with any of these statements (ACCEPT NO OTHER RESPONSES) ....................................................................................................................................................................................... 8
  • Not sure (ACCEPT NO OTHER RESPONSES) ......................................................................................................... 9
• 6. When you come to prescribing, how often do you consider the licensed treatment option(s) available for the specific condition first?
  • Always ........................................................................................................................................................................... 1
  • Sometimes ...................................................................................................................................................................... 2
  • Occasionally ................................................................................................................................................................... 3
  • Rarely .............................................................................................................................................................................. 4
  • Never ............................................................................................................................................................................... 5
  • Don’t know ...................................................................................................................................................................... 9
• 7. Generally speaking, please indicate how comfortable you are prescribing an ‘unlicensed’ treatment (prescribing a treatment for a condition for which it has no license, is administered via a different route and/or formulation has been changed).
  • Very comfortable .............................................................................................................................................................. 1
  • Somewhat comfortable ..................................................................................................................................................... 2
  • Not very comfortable ........................................................................................................................................................ 3
  • Not at all comfortable ....................................................................................................................................................... 4
  • Don’t know ....................................................................................................................................................................... 9
• 8. In your opinion, which of the following, if any, do you believe are good reasons to select an unlicensed treatment over a licensed treatment for a specific condition? Please select all that apply. [RANDOMIZE. ACCEPT MULTIPLE RESPONSES.]
  • The unlicensed treatment is less expensive ....................................................................................................................... 1
  • The unlicensed treatment has fewer side effects ............................................................................................................... 2
  • The licensed treatment has been tried and did not work ................................................................................................... 3
  • There is no licensed alternative ......................................................................................................................................... 4
  • None of these ..................................................................................................................................................................... 8
  • Don’t know ........................................................................................................................................................................ 9
• 9. To what extent do you agree or disagree with the following statement? [ACCEPT SINGLE RESPONSE.]
  It is never appropriate to prescribe an unlicensed treatment if a licensed treatment is available
  • Strongly agree .................................................................................................................................................................... 1
  • Somewhat agree ................................................................................................................................................................. 2
  • Somewhat disagree ............................................................................................................................................................. 3
  • Strongly disagree ................................................................................................................................................................ 4
  • Don’t know ......................................................................................................................................................................... 9

To what extent are you concerned with each of the following when it comes to prescribing unlicensed medications? (RANDOMIZE)

• 13. Before today, how familiar would you say you were with the following GMC guidelines regarding prescribing unlicensed treatments?
  “An unlicensed drug should not be used in a condition where a licensed drug is available. When an unlicensed medicine is used, it raises questions on how reporting, interpretation, and the management of adverse events will be undertaken”
  • Very familiar .................................................................................................................................................................... 1
  • Somewhat familiar ............................................................................................................................................................ 2
  • Not very familiar ............................................................................................................................................................... 3
  • Not at all familiar .............................................................................................................................................................. 4
  • Don’t know ....................................................................................................................................................................... 9
• 14. Who, if anyone, do you think would be held responsible if a problem occurred following the use of an unlicensed treatment? Please select all that apply. [RANDOMIZE. ACCEPT MULTIPLE RESPONSES.]
  • The individual prescriber ................................................................................................................................................... 1
  • The patient ......................................................................................................................................................................... 2
  • The PCT manager or hospital trust .................................................................................................................................... 3
  • The lead physician responsible for a patient s care ........................................................................................................... 4
  • The hospital pharmacist ..................................................................................................................................................... 5
  • None of these ..................................................................................................................................................................... 7
  • No one would be held responsible ..................................................................................................................................... 8
  • Don’t know ........................................................................................................................................................................ 9

In the current economic climate, the National Health Service is being challenged to identify areas where cost savings can be found. Within this, expenditure on drugs has been identified as one route to reducing annual NHS expenditure.

• 15. What impact, if any, do you think the current NHS focus on cost saving will personally have on your prescribing choices:
  • It will have a significant impact on my prescribing choices............................................................................................... 1
  • It will have some impact on my prescribing choices.......................................................................................................... 2
  • It will have no impact at all................................................................................................................................................. 3
  • Don’t know......................................................................................................................................................................... 9

Taking into account the aforementioned anticipated changes to the NHS expenditure on drugs, to what extent are you concerned with each of the following when it comes to using unlicensed medication? (RANDOMIZE)

Thank you for participating in this brief survey. This survey is strictly for research purposes, and should take no more than 10 minutes of your time. It is not intended to promote the sale of any product or device, and you will not be contacted for marketing purposes as a result of participating. Your responses will be kept confidential and anonymous, and nothing you say will be attributed to you personally.

It is required that we pass on details of adverse events that are mentioned during the course of market research. (By “adverse events”, we mean side effects or other consequences of your treatment or medication.) Although all your responses will, of course, be treated in confidence and anonymously, should you mention an adverse event during the interview, we will need to report this, even if it has already been reported by you directly to your physician, to the manufacturer, or to any regulatory authority.

In such a situation you will be asked whether or not you are willing to waive the confidentiality given to you under the Market Research Code of Conduct specifically in relation to that adverse event. Everything else you mention during the course of the interview will continue to remain confidential, and you will still have the option to remain anonymous if you so wish.

• Are you happy to proceed on this basis?
• Yes – Continue
• No – Thank you and close
• First, some questions to confirm that you qualify for the study.

• 19. Are you…?
  • Male .............................................................................................................................................................................. 1
  • Female ........................................................................................................................................................................... 2
• 20. What is your current age? [TERMINATE IF NOT AGE 18+.]
  • Enter your age here: .................................................................................................................................__ __ years old
• 21. Where do you live?
  • North East ...................................................................................................................................................................... 1
  • North West ..................................................................................................................................................................... 2
  • Yorkshire and Humberside ............................................................................................................................................ 3
  • East Midlands ................................................................................................................................................................ 4
  • West Midlands ............................................................................................................................................................... 5
  • East of England .............................................................................................................................................................. 6
  • London ........................................................................................................................................................................... 7
  • South East ...................................................................................................................................................................... 8
  • South West .................................................................................................................................................................... 9
  • Wales ........................................................................................................................................................................... 10
  • Scotland ....................................................................................................................................................................... 11
  • Northern Ireland .......................................................................................................................................................... 12
  • Channel Islands ........................................................................................................................................................... 13
  • None of these ........................................................................................................................................ .[TERMINATE]

To what extent do you agree or disagree with each of the following statements? [RANDOMIZE]

• 26. When your doctor prescribes medication to you, how often do you ask questions about the medication?
  • Frequently ............................................................................................................................................................. 1
  • Often ..................................................................................................................................................................... 2
  • Rarely .................................................................................................................................................................... 3
  • Never ..................................................................................................................................................................... 4
  • Don’t know ............................................................................................................................................................ 8
  • My doctor never prescribes medication to me ....................................................................................................... 9
• 27. Which of the following comes closest to your opinion, to the best of your knowledge? (RANDOMIZE FIRST TWO OPTIONS)
  
  • Doctors can prescribe any medication they choose to treat a condition ................................................................. 1
  • Medication can only be prescribed for a condition if it has been approved for that specific condition .................................................................................................................................................................................. 2
  • Neither of these ........................................................................................................................................................ 8
  • Don’t know .............................................................................................................................................................. 9
  To receive a license for use in a particular condition, medicines must undergo strict regulatory processes. Once licensed, they continue to be subject to the UK’s safety monitoring and reporting procedures.
  If a medicine is used outside of its license (for a medical condition for which it doesn’t have a license), it is not subject to the same robust safety procedures.
• 28. How much would you say you know about the regulatory process that all medications need to go through to gain a license to be prescribed to patients?
  • A great deal ............................................................................................................................................................. 1
  • Some ....................................................................................................................................................................... 2
  • A little ..................................................................................................................................................................... 3
  • Nothing at all .......................................................................................................................................................... 4
  • Don’t know ............................................................................................................................................................. 9
• 29. When your doctor prescribes medication for you, what do you think are the most important factors about the medication that your doctor should consider.
  Please rank each of the factors below from 1 to 4, where 1 means it is the most important, 2 is the second most important, and so on. You can only use each number from 1 to 4 once. [RANDOMIZE ORDER OF ITEMS]
  • It works ............................................................................................................................................................. _____
  • It is safe ............................................................................................................................................................. _____
  • It is not expensive ............................................................................................................................................. _____
  • It is easy to take or administer .......................................................................................................................... _____
• 30. To the best of your knowledge, in which of the following situations would you think it acceptable for a doctor to prescribe you with a medication that wasn’t approved for a particular condition you might have (unlicensed) rather than medication licensed and approved for use for the condition (licensed)? Please select all that apply. [RANDOMIZE. ACCEPT MULTIPLE RESPONSES.]
  • If it is less expensive .................................................................................................................................................. 1
  • If the licensed medication has been tried first ............................................................................................................ 2
  • If there were no alternative treatment options ............................................................................................................ 3
  • If it is proven to be more likely to work for me than the licensed medication ........................................................... 4
  • If it is proven to have fewer side effects than the licensed medication ...................................................................... 5
  • None of these .............................................................................................................................................................. 8
  • Don’t know ................................................................................................................................................................. 9
• 31. If you were prescribed an unlicensed treatment when a licensed treatment is available, how would you feel? Please select all that apply. (RANDOMIZE.)
  • I would not have a problem with it – I trust my doctor ............................................................................................... 1
  • I would ask some follow up questions to learn more, then make a decision ............................................................... 2
  • I would be dissatisfied with my doctor ........................................................................................................................ 3
  • I would stop taking or refuse to take the treatment immediately ................................................................................. 4
  • None of these ................................................................................................................................................................ 8
  • Don’t know ................................................................................................................................................................... 9
• 32. If your doctor prescribed you a treatment that is not licensed for your specific condition, specifically because it costs less that a licensed alternative, how concerned would you be about its safety?
  • Very concerned .............................................................................................................................................................. 1
  • Somewhat concerned ...................................................................................................................................................... 2
  • Not very concerned ......................................................................................................................................................... 3
  • Not at all concerned ........................................................................................................................................................ 4
  • Don’t know ..................................................................................................................................................................... 9