Information Required Before Using Medicine

Published Date: 02 Nov 2017

ACKNOWLEDGEMENTS ii

LIST OF ABBREVIATIONS iii

ABSTRACT iv

1.INTRODUCTION 1

1.1 PATIENT INFORMATION LEAFLET (PIL) 1

1.1.1 PIL BACKGROUND INFORMATION 1

1.1.2 LAYOUT OF PIL 2

1.1.3 IMPROVING PIL READABILITY 2

1.1.4 LINK BETWEEN PIL AND NOCEBO EFFECT 4

1.2 NOCEBO EFEFCT 5

1.2.1 NOCEBO EFFECT DEFINTION 5

1.2.2 NOCEBO EFFECT MECHANISM 6

1.2.3 FACTORS AFFECTING NOCEBO EFEFCT 6

1.2.4 NOCEBO EFFECT IN CLINICAL STUDIES 8

2.AIM AND OBJECTIVES 10

2.1 AIM 10

2.2 OBJECTIVES 10

3.METHOD 11

3.1 ETHIC APPROVAL 11

3.1 POSTER 11

3.2 ETHICS FORMS 12

3.3 QUESTIONNAIRE 16

3.4 PIL 17

3.4.1 PIL GROUP A 18

3.4.2 PIL GROUP B 19

3.4.1 PIL GROUP C 20

3.5 INTELLIGENCE QUOTIENT (IQ) TEST 21

3.5.1 IQ TEST VERSION 1 22

 3.5.2 IQ TEST VERSION 2 25

3.6 POST QUESTIONNAIRE 28

3.7 DEBRIEF 30

3.8 LIMITATIONS OR DIFFICULTIES ENCOUNTERED 31

ACKNOWLEDGEMENTS

I would like to thank Dr Fletcher for his guidance during crucial steps of this project.

I also thank my friends and family who have supported me.

LIST OF ABBREVIATIONS

ACC Anterior cingulate cortex

ACTH Adrenocorticotropic hormone

AMAS Aston Medication Adherence Study

API Active Pharmaceutical Ingredient

CCK Cholecystokinin

CSM Committee on Safety of Medicines

EC European Commission

EU European Union

GI Gastrointestinal

GP General practitioner

GPhC General Pharmaceutical Council

HCP Healthcare Professional

IQ Intelligence Quotient

MA Market Authorisation

MHRA Medicines and Healthcare products Regulatory Agency

p probability (statistical)

PFC Prefrontal cortex

PIL Patient Information Leaflet

SPC Summary of Product Characteristics

ABSTRACT

INTRODUCTION

1.1 PATIENT INFORMATION LEAFLET (PIL)

1.1.1 PIL BACKGROUND INFORMATION

Before the Nocebo effect can be explained, Patient Information Leaflet (PIL) will be discussed. From 1999, every medicine sold in the UK must lawfully be provided with a PIL, regardless of method of buying. There are three main ways that a person can obtain a medicine1:

A non-pharmacy physical setting where there is no Healthcare Professional (HCP) involved in the transaction

Sold over the counter in a General Pharmaceutical Council (GPhC) registered pharmacy physical premise by or under the supervision of a pharmacist

Through prescription dispensed involving a pharmacist in a GPhC registered physical pharmacy

Another method that is becoming popular is from online Pharmacy retailers (i.e. ChemistDirect2) where limited advice is imparted regarding the medicine.

The Summary of Product Characteristics (SPC) contains comprehensive information about a medicine such as data pertaining to clinical trials, pharmacological, pharmacodynamics and pharmacokinetics plus an extensive list of reported side effects. The language used in the SPC is scientific and so aimed at HCPs like pharmacist, general practitioners (GPs) and nurses. PIL is effectively a patient friendly summary of the SPC and contains six key sections. (See Table 1 below)

People are unlikely to retain all the information that a pharmacist or a trained healthcare assistant conveys to them, even if a pharmacist is involved in selling of medicines. Therefore, a PIL can enhance (but not replace) advice obtained regarding the corresponding medicine from the Pharmacist.1 An Ipsos Market & Opinion Research International (MORI) survey of 1,864 British adults revealed that PIL is regarded as the third most reliable source of medicine information after medical doctors and pharmacist. Internet sources were fifth on the list but information online is often not regulated and can be anecdotal.3 A study showed that the four key sections a patient looks at from a PIL are side effects, the indication of drug, the dos and don’ts and the frequency the medicine should be taken. 3. Berry D C,

1.1.2 LAYOUT OF PIL

PIL must follow Title V of Council Directive 2001/83/EC standards edited by Council Directive 2004/27/EC and Council Directive 2010/84/EU and is controlled by Patient Information Quality, which is part of the Medicines and Healthcare products Regulatory Agency (MHRA) in the UK.1

Table 1: Six sections of PIL as outlined by Article 59 of 2001/83/EC

Section

Section Title

Information included in particular section

1

Identification of medicine and therapeutic indication

Drug name with form and strength and

medical condition(s) the medicine is authorised for

2

Information required before using medicine

Any cases when medicine must not be used,

drug interactions and if medicine is safe for pregnant or breast feeding woman.

3

Dosage instructions

Recommended route and frequency the medicine can be taken and the procedure if a dose is missed, overdose taken or sudden withdrawal effects (if relevant)

4

Side effects

Significant harmful effects of the medicine reported in order of probability. Adverse drug reactions (if relevant)

5

Storage conditions

Where the medicine should be kept at home (i.e. cool dry place or fridge)

6

Additional Information

Drug excipients, name & address of Market Authorisation Holder (MAH) and date PIL written or updated.

1.1.3 IMPROVING PIL READABILITY

There are also layout guidelines in Article 59(1) which including information on headings, font, colour, ordering of side effects and use of lay colloquial English language. A summary of recommended writing style, typeface and heading format is listed below:

Simple words of few syllables and sentences of less than 20 words

Use of bullet points (6 max in one list) instead of paragraphs

60-70 characters per line

Serif typeface font with font size 14 (headings) and 12 (main text) point

Avoid italics and underlining

Problems with PIL

As stated before, PIL is regulated by European union (EU) and national guidelines but there is still variability in the quality of PILs including PIL readability as indicated by a score from CSM Quality criteria for PILs . (Ab page 3) In 2003, the Committee on Safety of Medicines (CSM), Consumers’ Association (now Which?) and the National Audit Office asked for improvements in the quality of PIL. Some of the suggested improvements were to simplify PIL more (so patient does not miss important information) and increase patient understanding of risk of side effects used by HCP. (likelihood of side effect is perceived to be higher by patients) In 2004, CSM arranged a meeting with patients, carers and voluntary organisation to collate their thoughts on PIL such as:

Too much jargon and much negative information with not enough benefit of medicine

The information on PIL should reflect conversation with HCP

One PIL for all patient needs is not sufficient so there should be signposting to other sources like trusted organisations, websites and helplines

Supplementary information on lifestyle should be provided where appropriate (i.e. cholesterol medication)

Group target patients

From July 2005, the PIL of any new medicine must be tested by the MAH with a group target patients as outlined in Article 59(3) of 2001/83/EC.1 The minimum of 20 target patients can include people who occasionally take medication and young and elderly people. The test is successful when 90% of the patients can find the information requested and 90% of these comprehend the information.

Improve risk communication

To coincide with this new law, the CSM’s Working Group on Patient Information produced new improved guidance on the usability of PIL in areas like risk communication providing guidance on how to display side effects. This guidance included a glossary of side effects in lay language. (i.e. use of sleepiness instead of drowsiness) Section 4: Side Effects have a variability of representation of information as there is no EU guidance on how it should be displayed. Side effects can be ordered by verbal descriptors or numerically but CSM guidelines state that very severe or unwanted side effects should be listed regardless, especially if patient needs to seek medical help to combat the side effect. The appropriate words should be used "immediately" if urgent or "as soon as possible" or patients should be encouraged to report any other side effects not listed in PIL.

CSM also recommends that side effect risk should be mentioned numerically and at the moment, a larger proportion of PIL contains verbal descriptors. The verbal descriptors and numerical counterpart is shown in Table 2 below and research has shown that risk is overestimated in the patient’s mind. For example a common side effect (1 in 10) is thought to be around 1 in 6.

Table 2: Verbal descriptor and numerical side effect risk ref Ab risk SE

Verbal Descriptor

EU recommended numerical frequency

Very common

more than 10% (more than 1 in 10)

Common

more than 1% and less than 10% (less than 1 in 10 but more than 1 in 100)

Uncommon

0.1% to 1% (less than 1 in 100 but more than 1 in 1000)

Rare

0.01% to 0.1% (less than 1 in 100 but more than 1 in 1000)

Very rare

up to 0.01% (less than 1 in 10,000)

1.1.4 LINK BETWEEN PIL AND NOCEBO EFFECT

As stated before, a PIL must be harmonised with the Summary of Product Characteristics and so must not omit important information from the public. 1 After obtaining a medicine, one can read the side effects (some derived from preliminary data) on the PIL and may seek additional information from HCPs or internet. The side effects stated can trigger negative thoughts (especially after visiting internet sites) that inevitably could consciously or sub-consciously lead to the nocebo effect. (explained below)

Non adherence

A debate between a balance of comprehensive and necessary information on a PIL could be established if the nocebo effect is considered.21 Comprehensive warnings and side effects about medicine can influence an individual to discontinue medication but too little information on PIL can lead lost in trust in medication and/or HCP. (if HCP was involved in selling and/or recommending of medicine)

Non-adherence to medication is a major problem in the UK and is estimated that it costs NHS more than £500 million each year from the premier large scale (1 million prescriptions, 7,000 patient questionnaires and 7 focus groups) adherence project by the Aston Medication Adherence Study (AMAS). (REFERENCE)The study showed that 1 in 3 to 1 in 4 people living in Birmingham were non adherence to medication particularly diabetes, dyslipidaemia and hypothyroidism sufferers.

One rationale behind this high number was medication side effect anxiety and suggested a better understanding and information of medicines in the socially deprived areas of Birmingham are needed. Other reasons included variations of generic forms of medicine supplied by pharmacist and low number of symptoms from the diagnosed condition. Although further research is needed, some suggestions (like better comprehension of medicine) could be extended to rest of the UK.

Throughout rest of Europe, non-adherence is also a problem. In a MEDLINE and EMBASE (between 1989 and 2009) search in Germany, around 2 in 3 people understood the need for generic substitution but up to 1 in 3 people reported more nonspecific side effects as they though cheaper drugs were not as effective and more harmful. Once again, suggestions were made that patients were not armed with sufficient information from HCPs about generic prescribing. (REF)

The consequences of non-adherence are decreased quality of life, lower life expectancy and more avoidable admissions to hospital so there is an obvious reason why HCP must reduce the non-adherence rates. (REF NPC.NHS) 4

1.2 NOCEBO EFEFCT

1.2.1 NOCEBO EFFECT DEFINTION

The ‘placebo effect’ (taking an inert drug thinking it will have a positive effect) is an established term used mainly in trials. However, it is estimated that quarter of subjects link adverse side effects to the inert drug.4 This is classed as the ‘Nocebo effect’ and is the lesser recognised undesirable counterpart of the placebo effect. This term can be extended to any side effect patient (i.e. listed in PIL) thought to be linked to the Active Pharmaceutical Ingredient (API) of a drug, but not supported by physical evidence in that specific individual. (independent of drug pharmacological properties)

While the term was created by Walter Kennedy5 in 1961, significant interest and differentiation (from the placebo effect) of the nocebo phenomena arose in 1990s but its use in the medical setting is minimal due to ethical issues of causing harm (i.e. stress or anxiety) to patients. If HCPs are more aware of this effect, their wording (i.e. "high risk") of negative effects of medicines could be altered, whilst still acting within the best interest of the patient and not omitting vital information.6

Nocebo effect can be fatal as shown in the 1970s where a man died within the time frame predicted by doctors but later revealed he was incorrectly diagnosed with terminal liver cancer and cancer had not metastasised.7

1.2.2 NOCEBO EFFECT MECHANISM

Cholecystokinin (CCK) is the most studied neurotransmitter involved in the nocebo effect involving pain. CCK-A and/or CCK-B receptors are stimulated when pain expectation is verbally expressed to the subject (leading to hyperplasia) compared to increase in endogenous opioid when stated that pain will improve (placebo). 10, 11 There have been studies showing CCK antagonist (i.e. proglumide) can inhibit the nocebo hyperplasia effect but not hypothalamus pituitary-adrenal hyperactivity releasing Adrenocorticotropic hormone (ACTH) and cortisol (stress hormones). Conversely, benzodiazepine can inhibit both pathways showing link to anxiety. 12 Therefore, two different biochemical pathways for nocebo effect have been proposed as represented in Figure 1 below.

Figure 1 Nocebo Effect Mechanism 13

Decreased D2-D3 dopamine and µ-opioid neurotransmitter levels in nucleus accumbens, showed connections with nocebo effect in more recent times. 14

There have been four parts of the brain shown to be activated in the expectation of pain namely; insula, anterior cingulate cortex (ACC), prefrontal cortex (PFC) and thalamus.15 Consequently, more research is required, so scientists could produce new drugs that targeted specific parts of the brain and hopefully help to improve compliancy linked to pain.

1.2.3 FACTORS AFFECTING NOCEBO EFEFCT

Psychological conditions

Power of suggestion can lead to people reporting nonspecific side effects, especially people who are more prone to physiological traits such as anxiety, depression, somatisation (neurological process of emotional presenting as physical symptoms) and hypochondriacs.4

A randomized double blind trial (involving 105 patients) treating fatigue in advanced cancer, showed that people who suffered from anxiety and depression had a higher chance of reporting restlessness and tachycardia respectively. (REF Cancer. )

Gender and Age

In general, females and elderly are more likely to report nocebo effects. 9 (REF 8. Hrobjartsson A, Gotzsche PC) Journal of Psychosomatic Research 66 (2009) 323–328 Gender and

One study showed that it 30% females compared to 19% males reported nocebo effect (p= 0.01). A reason why elderly may report nocebo effect could be due to polypharmacy.

Shape and colour of medicine

It has been suggested that the shape and/or colour of medicine can influence participants’ side effects, concluding that blue and green represented drowsiness and red, orange and yellow pills were thought induce a stimulant effect.4

Past negative exposure to medicine

Someone who experienced a side effect from the same or similar drug in the past could be pre-conditioned to report nocebo effects. 4 (REF EVALUa)

Increased Awareness

A study suggested that individuals have an increased awareness of any changes in the body during illness. 4 Therefore, any symptom(s) while on medication is automatically connected (subconsciously) to the medicine and in some cases; it can be a symptom one would acquire normally from time to time even without the medication.

Relationship with HCP

Another factor is that situational settings and relationship with HCP, as little contact with a HCP can increase the chance of the nocebo effect.(4)

1.2.4 NOCEBO EFFECT IN CLINICAL STUDIES

One early double blind study involved 20 asthmatic participants to inhale a bronchodilator called isoproterenol (widen airways) but misinformed half of the participants that it was a bronchoconstrictor (told it would narrow airways). The conductance-thoracic gas volume ratio (measure of lung function) was calculated and shown that it was increased by only 20.1% (misinformed group) compared to 39.6% (other half) with p=0.02 (p<0.05) showing the nocebo effect was statistically significant.16

A randomised three centre trial of unstable angina sufferers showed that minor gastrointestinal (GI) side effects was six times more probable (p<0.001) when this side effect was mentioned in the consent form of aspirin or sulfinpyrazone than when omitted. The GI symptoms were so vast in few nocebo patients that they opted out of study.18

Another study featured females, proposed that independent from risk factors, the death rate for women who thought they were more disposed to heart attacks was 3.7 times higher.17

Studies on adverse sexual effects have also been carried out. (8, 36, 37). A well-known study involving finasteride drug given to 127 benign prostatic hyperplasia patients who were sexually active split into two groups. Group 1 were told the drug may cause decreased libido, erectile dysfunction and difficulties in ejaculation, while the group 2 were not given any adverse side effects. At 6 and 12 months after administration, it was noted group 1 complained significantly more sexual dysfunction effects (44% and 15% for group 1 and 2 respectively, p=0.03)

In an anti-migraine medication Medline/PubMed or CENTRAL search consisting of 73 clinical placebo controlled trials published until 2007, the reported side effects of the placebo groups were investigated. It was concluded that a high number of side effects and even adverse side effects like anorexia and memory problems (which can be experienced by patients taking anticonvulsants) were surprisingly reported by the placebo groups. (REF ANTI)

A three centre trial in Italy of 600 participants (Age 7-76 years old) with a past reaction to drugs showed that the average nocebo effect was 27% with no significant difference between the three centres. (chi-square, p= NS).Two thirds of the side effects were nonspecific symptoms like itching, dizziness and headache. (REF Evaluation of the nocebo)

Non-specific side effects can be caused by cancer patients today by reading the consent forms listing side effects, for example anticipatory nausea from radiotherapy. 8 The side effects are thought be felt in the early weeks of treatment and can be reduced by the HCP telling patient that it will subside and highlighting benefits of treatment.

A recent study involving thermal pain signals in Massachusetts, even showed that unconscious negative thoughts about medication existed before any information (verbal or visual) about the medicine were conveyed. A link was been proposed to the striatum, amygdala and primitive parts of the brain.19

A further recent study in University of New South Wales, Australia (82 people, 3:1 female to male ratio) claimed a new medication could improve sleep difficulties in one week. 20There were two groups which received verbal and written warnings about side effects; one side effect (group 1) and four side effects (group 2) while no side effects were mentioned in the third controlled group. Participants experienced the side effect (i.e. decreased appetite) conveyed to them at start of experiment (p=0.001)

AIM AND OBJECTIVES

As described before, the power of suggestion can be powerful and can produce placebo-induced side effects. This project is essentially testing the nocebo effect from PIL.

2.1 AIM

The aim of this project will be to investigate the nocebo phenomena caused by side effects listed in a PIL.

2.2 OBJECTIVES

During the project, the following objectives will be fulfilled:

Investigate if listing side effects of an inert drug (placebo) influences the amount of side effects reported.

Evaluate differences in age and gender in reporting nocebo effect.

How people interpret the verbal descriptor side effect risk "common" numerically.

METHOD

3.1 ETHIC APPROVAL

As this project required human participants and there was deception involved, (participants think they are taking tablet that will improve their Intelligence Quotient (IQ) and the un proven side effects listed in PIL) ethics approval was required. This methodology was approved by delegates of Ethics Committee (Dr Reem Kayyali and Dr Nick Freestone) in Kingston University in late January 2013. (See Ethics approval forms in Appendix)

Placebo Drug

The inert pill that subject took was 3 x vitamin C 500mg tablets (one tablet a day) as it has a low evidence of efficacy (REF) The subjects were observed taking the first dose.

3.1 POSTER

Once ethics was approved, Kingston university students were recruited through posters around prominent position around the university (i.e. display board in Town House, main building ground and second floor) There was an entry to £20 prize draw for participants that enter as an incentive to take part. There were two rooms booked on Wednesday (from 12/02/13 to 20/03/13) and Friday (from 08/02/13 to 22/03/13), so people can complete the IQ test in quiet. However, if participants were unavailable on Wednesday or Friday, the experiment was carried out in other quiet areas like the library.

3.2 ETHICS FORMS

K number:

Participant Information sheet

You are being invited to take part in a MPharm final year project. Before you decide whether or not to take part, it is important for you to understand why the research is being done and what it will involve. Please take time to read the following information sheet carefully before deciding whether or not to participate. If you consent to take part, then you will be asked to sign an informed consent form. If you decide not to take part there will be no disadvantage to you and we thank you for your time in considering our project. If after reading this information sheet, you are still unsure or uncertain about anything, then I am happy to answer any questions you may have. You should not sign the consent form until your queries have been resolved and you are happy to volunteer.

What is the purpose of the study?

The primary aim of this study is to test if a new pill can increase intelligence.

Why have I been chosen?

Students are ideal audience to test this new drug as they are studying and this pill can help them in their studies.

Do I have to take part?

No. This research study is done purely on a voluntary basis. If you choose to take part after reading this information sheet, I will ask you to sign a consent form. You are free to withdraw from this study at any point without disadvantage and without having to provide a reason.

What will happen to me if I take part?

You will be asked to complete a short questionnaire, sit a short IQ test and take 3 tablets of the new medicine over 3 days. Then you will be invited to come back and fill out a post questionnaire and sit another IQ test.

What are the possible benefits of taking part?

This drug can improve your intelligence and could help you if your job interview requires verbal, numerical reasoning test.

What are the possible disadvantages and risks of taking part?

There maybe some side effects of the medicine.

What happens when the research study ends?

You will be under no obligation to volunteer again. Contact details for myself/ourselves plus project supervisor are included at the end of this information sheet should you wish to discuss the findings.

Will my taking part be kept confidential?

All information collected during the course of the study will be kept strictly confidential and in secure storage. Responses will be anonymised before analysis so that it will not be possible to identify you or any other participant. Only I and the project supervisor will have access to this dataset.

Any personal information collected will be immediately destroyed, except that required by the

University research policy.

Who is organising and funding the study?

This study is part of my final year project for Maters of Pharmacy (MPharm) degree, within the School of Pharmacy, Faculty of Science, Engineering and Computing at Kingston University. None of the investigators stands to gain financially from this study.

What will happen to the results of the research study?

The results will be part of my dissertation which will be made available in the Faculty of Science Learning Resources Centre (library) at Kingston University for others to view. In addition, findings arising from this study may be presented at national and international conferences as well as published in scientific journals. It will not be possible to identify you or others from any such publications with results being aggregated for the whole group. In such cases where an interview is used, if you permit for the interview to be recorded and transcribed, participants will always be referred to by pseudonyms.

Please contact me or my supervisor Dr Fletcher if you have any questions about this project.

Who has reviewed the study?

The Kingston University Faculty of Science, Engineering and Computing Research Ethics Committee has reviewed and approved this study.

In addition, this project is being supervised by Dr John Fletcher.

Contact for further information.

Further information may be obtained from:

Researcher Details: Dawar Qhoraish, [email protected]

Supervisor Details: Dr John Fletcher, Room Pr-218,Penrhyn Road, [email protected], phone:62192

If you become concerned about any issue that may have been raised by you participating in this study, please contact Dr John Fletcher

Thank you for taking the time to read this information sheet

CONSENT FORM

I have been fully briefed and am willing to take part in this experiment involving taking three doses of the drug (Smartiq). I understand that my data will be confidential. I give permission for the researcher to use the data collected from this experiment to be used as part of his project. I am under no obligation to finish the experiment and can opt out at any time.

Participant Full name

Participant Signature

/

Date

Thank you

Researcher Name : Dawar Qhoraish

Researcher email: [email protected]

Supervisor Name: Dr John Fletcher

Supervisor email: [email protected]

3.3 QUESTIONNAIRE

There was a pre questionnaire to rule out subjects with clinically diagnosed anxiety and depression as this can affect nocebo effect.

Questionnaire

Are you currently taking any medication(s)?

Yes No

Are you currently taking any medication(s)?

Are you currently taking any medication(s)?

If yes, please state which medication(s) below and inform the researcher

Do you have any illnesses or diseases?

Yes No

If yes, please state which illness or disease below:

Are you currently taking any medication(s)?

Are you currently taking any medication(s)?

Do you have any known allergy/allergies to any food or medication?

Yes No

Are you currently taking any medication(s)?

Are you currently taking any medication(s)?

If yes, please state which allergy/allergies below:

What do you think your IQ is?

70-90 (Below normal) 110-119 (Above normal)

90-109 (Normal) 120-140 (Very intelligent)

160+ (Genius)

What is your gender?

Male Female

What is your age?

18-24 25-30

31-40 40+

3.4 PIL

A fictional simple PIL was created following the guidelines in 2001/83/EC and Quality criteria for PILs.1,22 Participants were split into three groups; first two groups will contain two opposing non-psychological side effects as carried out in other study 20 (i.e. diarrhoea and constipation & increased and decreased appetite) and third group PIL will not contain any side effects. Group A displayed the likelihood of side effect numerically compared to verbal descriptor in group B.

The side effects were carefully chosen to be non-specific as these were reported in the clinical studies of nocebo effect (See 1.2.4) and are summarised in table 3 below.

Table 3 Summary of side effects listed in fictional PIL

Side Effect

PIL group

Brief description(12)

Some non-drug related cause(s)(12)

Diarrhoea

A

Loose bowel movements.

Uncooked meat, Poor hand hygiene

Constipation

B

Decreased bowel movements

Low fibre diet

Increase appetite

A

Urge to eat more than usual

Low sugar level

Decreased appetite

B

Lower desire to eat than usual

Smoking

Headache

A and B

Pain in head or upper neck

Stress, weather

Fatigue

A and B

Lack of energy

Insufficient sleep

Itching

A and B

Urge to scratch

Allergy, insect bite

Insomnia

A and B

Inability to sleep normally

Caffeine, stress

Dry mouth

A and B

Lack of production of saliva

Dehydration

The study was a randomised double blind study. Subjects were randomised into one of the three groups by a random 1-90 number order generator carried out by the supervisor. The matching of the participant number to specific group was kept blind to the researcher until the end of recruitment.

A potential issue could arise when people carried out the first step of the experiment as a group and discussed the side effects listed in the PIL they were given and realised they were different. Therefore, the IQ test was given before and after taking three vitamin c tablets so people could quantify the placebo effects.

The three PIL are in the subsequent three pages.

3.4.1 PIL GROUP A

PATIENT INFORMATION LEAFLET FOR Smartiq

Please read of all of this leaflet carefully because it contains important information.

In this leaflet:

What is this medicine and what is it used for?

Before you take this medicine

How to take this medicine

Possible Side Effects

Storing this medicine

What is this medicine and what is it used for?

This medicine contains natural ingredients that can increase your intelligence.

Before you take this medicine

This medicine can only be taken for adults aged 18 and over.

How to take this medicine

Swallow one tablet every day with water.

Possible Side Effects

Affects less than 1 in 10 but more than 1 in 100: Diarrhoea, Headache, Increase appetite

Affects less than 1 in 100 but more than 1 in 1,000: Fatigue, Itching, Insomnia

Affects less than 1 in 1,000 but more than 1 in 10,000: Dry mouth

Storing this medicine

Store in a cool dry place (<25oC)

Keep out of the reach and sight of children

3.4.2 PIL GROUP B

PATIENT INFORMATION LEAFLET FOR Smartiq

Please read of all of this leaflet carefully because it contains important information.

In this leaflet:

What is this medicine and what is it used for?

Before you take this medicine

How to take this medicine

Possible Side Effects

Storing this medicine

What is this medicine and what is it used for?

This medicine contains natural ingredients that can increase your intelligence.

Before you take this medicine

This medicine can only be taken for adults aged 18 and over.

How to take this medicine

Swallow one tablet every day with water.

Possible Side Effects

Common: Constipation, Headache, Decreased appetite

Uncommon: Fatigue, Itching, Insomnia

Rare: Dry mouth

Storing this medicine

Store in a cool dry place (<25oC)

Keep out of the reach and sight of children

3.4.1 PIL GROUP C

PATIENT INFORMATION LEAFLET FOR Smartiq

Please read of all of this leaflet carefully because it contains important information.

In this leaflet:

What is this medicine and what is it used for?

Before you take this medicine

How to take this medicine

Possible Side Effects

Storing this medicine

What is this medicine and what is it used for?

This medicine contains natural ingredients that can increase your intelligence.

Before you take this medicine

This medicine can only be taken for adults aged 18 and over.

How to take this medicine

Swallow one tablet every day with water.

Possible Side Effects

This drug is not known to have any side effects

Storing this medicine

Store in a cool dry place (<25oC)

Keep out of the reach and sight of children

3.5 INTELLIGENCE QUOTIENT (IQ) TEST

Improvement in IQ was chosen as Kingston university students are in academia and so are more likely to take part in a project if it indirectly assists with their studies. Participants sat a condensed version of an IQ test before and after the second dose of the inert pill to make the study more believable.

The IQ test questions were taken from one website which separated IQ in seven areas of intelligence: Verbal, mathematical, spatial, visualization, classification, logic and pattern recognition. (REF) The IQ tests questions were trialled out with 10 non Kingston university students to obtain a rough view of four easy questions, 5 medium difficulty questions and 5 hard questions.

The order of which IQ version was carried out first was partially randomised but if there were groups carrying out at same time, then the same IQ version was given to each person in the group. This is in case participants discussed questions and therefore the second IQ test mark will be biased. Although this project focuses of the nocebo effect, the placebo effect in terms of improvement of test mark was also analysed.

3.5.1 IQ TEST VERSION 1

IQ test

Instructions: You have 15 minutes to complete test. Please circle your answer

1. Rearrange the following letters to make a word and choose the category in which it fits.

RAPETEKA

A. city

B. fruit

C. bird

D. vegetable

2. Which one of the sets of letters below can be arranged into a five letter English word.

A. A T R U N

B. P O D E B

C. R N A S L

D. M O H A T

E. E T L R N

3. Which number should replace the question mark?

17

8

5

5

13

7

5

4

6

12

6

3

10

6

4

?

A. 4

B. 5

C. 6

D. 7

4. Library is to book as book is to

Binding Copy Page Cover

A. page

B. copy 

C. binding 

D. cover

5. Which diagram results from folding the diagram on the left?

6.  Pick the piece that's missing from the diagram below

A

B

C

D

7. Which word does not belong?

apple, marmalade, orange, cherry, grape

A. apple

B. marmalade

C. orange

D. cherry

E. grape

 

8. Which number does not belong?

4

32

144

17

28

122

18

64

188

322

14

202

32

17

122

202

322 

9.  Which of the cubes is the same as the unfolded cube below?

A

B

C

D

10. At the end of a banquet 10 people shake hands with each other. How many handshakes will there be in total?

A. 100

B. 20

C. 45

D. 50

E. 90

11. Which figure is the odd one out?

12. The day before the day before yesterday is three days after Saturday. What day is it today?

A. Monday

B. Tuesday

C. Wednesday

D. Thursday

E. Friday

13. Which number should come next in this series?

25,24,22,19,15

A. 4

B. 5

C. 10

D. 14

14. Find the picture that follows logically from the diagrams to the right.

 3.5.2 IQ TEST VERSION 2

IQ test

Instructions: You have 15 minutes to complete test. Please circle your answer

1. What is the missing letter?

E

C

O

B

A

B

G

B

N

D

B

?

K

H

L

O

M

2. Find two words, one from each group, that are closest in meaning.

Group A

raise

floor

stairs

Group B

top

elevate

basement

raise and elevate

raise and top

floor and basement

stairs and top

floor and elevate

3. How many four sided shapes does this diagram have?

A. 5-10

B. 11-15

C. 16-20

D. 21-25

E. 26-30

4. Which is the next number in the series: 4, 5, 8, 17, 44, ?

A. 80

B. 125

C. 112

D. 60

E. 84

5. Which of the following figures is the odd one out?

6. Which number should replace the question mark?

 

8

5

21

35

32

12

32

28

31

4

?

28

A. 3

B. -2

C. -6

D. 48

7. Which of the following figures is the odd one out?

8. Which of the following diagrams is the odd one out?

9. Please enter the missing figure: 13, 57, 911, 1315, 1719, ?

A. 2123

B. 1879

C. 3002

D. 5004

E. 1784

10. If you begin to fold along the dotted line, which of the following figures would follow the figure given below?

11. Which number should come next in the series

1, 3, 6, 10, 15,

A. 8

B. 11 

C. 24 

D. 21

E. 27

12. Which of the diagrams follows?

 

13. Which number should come next in this series?

3,5,8,13,21,

A. 4

B. 21

C. 31

D. 34

14. Find the picture that follows logically from the diagrams to the right.

 

3.6 POST QUESTIONNAIRE

A post experiment questionnaire was handed to subjects after three days of experiment. Side effect experienced, when they experienced side effect (if applicable) and their perception on the verbal descriptor "common" side effect risk was noted. Also, people were asked to review their thoughts of their IQ score and if they would buy the medication.

K number:

Post Questionnaire

Did you experience any side effect(s) whilst on this medicine? (Tick all that apply)

Itching

Diarrhoea Diarrhoea

Insomnia

Headache

Dry mouth

Increase appetite

Fatigue

Decreased appetite

Constipation

If other, please state below:

Before first tablet Diarrhoea

After first tablet Diarrhoea

When did you start experiencing this/these side effect(s)? (Tick all that apply)

After third tablet

ird tablet Diarrhoea

After second tablet Diarrhoea

If you were you suffering from any of the side effect(s) before you took the first tablet,

please state which below:

1 in 5 or less

Less than 1 in 10 but more than 1 in 50

What are the chances of someone experiencing a common side effect of a drug?

Less than 1 in 10 but more than 1 in 100

Less than 1 in 5 but more than 1 in 10

What do you think your IQ is now after taking the tablet?

70-90 (Below normal) 110-119 (Above normal)

90-109 (Normal) 120-140 (Very intelligent)

160+ (Genius)

No

Yes

Would you buy this medicine?

Please briefly expand on your answer below: (Use sheet overleaf if needed)

3.7 DEBRIEF

The subjects were debriefed on 26/04/13 about the true objectives of the study and the following was emailed to all participants.

Dear All,

Thank you for taking part in my project. The winner of the £20 Amazon voucher was participant number 10 and has been emailed.

Now that I have all my participants, I can reveal that the aim of my project was not to investigate if IQ score was improved but to test "Nocebo effect of Patient Information Leaflet (PIL)." The project was to investigate if people will are more likely to report side effects if listed in a PIL than if not listed in a PIL. Everyone was randomly put into three groups and each group contained different information on side effects section of the patient information leaflet. Group 1 had side effects including diarrhoea, increase appetite, whilst group two side effects were constipation and decreased appetite. (Two opposing side effects) Group 1 also listed the likelihood of a side effect in numbers (i.e. Affects less than 1 in 10 but more than 1 in 100) whereas, group 2 stated the chance of side effect in descriptive words. (i.e. common) Group 3 was the control group and did not have any side effects listed. Group 3 was the control group and no side effects were listed.

The "herbal drug" that you took was Vitamin C 500mg tablets which rarely has any side effects in the 500mg strength.

Although there has been some studies linking vitamin C with improvement in IQ scores, these studies have not been conclusive and mostly carried out in school children. Although vitamin C is crucial in brain development, it is unlikely that three low strength vitamin C tablets will improve IQ. Vitamins need to be taken for at least a few months to have an appreciable effect to the body and vitamins are not substitutes for vitamin C in diet. (i.e. oranges, strawberries, red and green peppers)

Increasing IQ is not easy and is not achieved in a few days. Some ways that you can gradually build up IQ include playing "brainpower" games (like scrabble), exercising regularly (increase visual stimulation) and sleeping an adequate amount of hours. (around seven hours)

Feel welcome to email me if you have any questions you have regarding this project or would like a summary of results.

The IQ tests that you carried out is attached in this email with answers.

Below are some online links relating vitamin C and IQ:

http://www.iqtestexperts.com/iq-vitamins.php

http://journals.cambridge.org/download.php?file=%2FPNS%2FPNS51_03%2FS0029665192000454a.pdf&code=c3338c551a6ccb5a9f1f376d4cb1ef35

http://www.cabdirect.org/abstracts/19911429980.html;jsessionid=414311EE79B8E8B23E60203D5669BE45?gitCommit=4.13.29

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2885294/

Below are some online links suggesting how IQ may be improved:

http://www.brainstrom.org/2012/07/26/want-to-make-yourself-smarter-here-are-a-few-scientifically-proven-ways/

http://www.articlesbase.com/self-improvement-articles/the-8-pillars-of-intelligencehow-to-increase-iq-1900438.html

http://www.fitbodyhq.com/mind/how-to-increase-your-intelligence/

http://science.howstuffworks.com/life/inside-the-mind/human-brain/5-ways-get-smarter.htm#page=0

3.8 LIMITATIONS OR DIFFICULTIES ENCOUNTERED

The main limitation with this project was quantity of participants. From the first two weeks, the participant number was low as people as many stated they did not have time for second part of the experiment even with the £20 prize draw money. Attempts were made from March to target participants in the main Kingston university canteen and corridors especially one or two hours before the start time of the booked rooms on Wednesday and Friday.

Females were hard to recruit as most were worried it will cause them harm and did not want to take the risk. Males were sceptical that wouldn’t work at all and it’s a placebo

Another problem was that ethics approval took longer than expected and recruitment could not start until early February.

Some participants may have taken vitamin C tablets before and recognised that the tablet was vitamin C (i.e. from the fruity smell) and therefore knew it was not a new pill.

Three people dropped out during the experiment. One while taking the first IQ test and two after taking the first dose. This made numbers in each of three groups uneven as they were randomised by the supervisor.