National Placebo Initiative

The Appropriate Use Of Placebos In Clinical Trials

Synthesis Report Of The Citizen Consultation On The Appropriate Use Of Placebos In Clinical Trials Held March To May, 2003

Submitted by the Public Involvement Coordinating Committee of the National Placebo Working Committee
January 2004
Sponsored by Health Canada and the Canadian Institutes of Health Research

Table Of Contents

Context
1. Dialogue Sessions
   1.1. The Approach
   1.2. Synthesis Report
   1.3. Participation
   1.4. Key Findings
      1.4.1. A Role For Placebo-Controlled Trials
      1.4.2. Selective Use Of PCTs
      1.4.3. Integration Of The Three Approaches
      1.4.4. A Trustworthy System
      1.4.5. Patient Autonomy
      1.4.6. Patient Protection
      1.4.7. Rigorous Science Within An International Context
      1.4.8. Access To New Drugs
      1.4.9. The Role Of Research Ethics Boards
   1.5. Learning From The Scenarios
   1.6. Evaluation
   1.7. Conclusion
2. Alternative Feedback Guide
   2.1. Participation
   2.2. Key Findings
   2.3. Evaluation
Appendix 1: Sample Agenda For The Dialogue Sessions
Appendix 2: Participant Chart For The Dialogue Sessions

The Appropriate Use Of Placebos In Clinical Trials Synthesis Report Of The 2003 Citizen Consultation

Context

In 2001, Health Canada and the Canadian Institutes of Health Research launched the National Placebo Initiative. It arose out of the recognition that there were two policies that had different definitions for the appropriate use of placebos in clinical trials¹. The goal of the Initiative is to promote the development of a common placebo policy through stakeholder and public consultations.

A National Placebo Working Committee (NPWC) was established to assist in this work. It was given the mandate to write a report including recommendations for the appropriate use of placebos. The committee's final report will include a response to the findings of the citizen consultation².

A sub-group of the NPWC coordinated the public consultation. This group, called the Public Involvement Coordinating Committee (PICC), developed a two-part consultation process with citizens. The first part consisted of five dialogue sessions held between March and May 2003. The sessions took place in Edmonton, Vancouver, Halifax, Montréal and Ottawa. The second part, called the Alternative Feedback Guide, was a redesign of the dialogue guide to allow individual input, either via the Internet or on paper.

1. Dialogue Sessions

   1.1 The Approach

The process chosen for the sessions was deliberative dialogue. One World Inc, a Canadian expert in this methodology, was contracted to design and implement the dialogue sessions.

Deliberative dialogue is a structured, facilitated process that helps people work through important issues. In such a dialogue, participants reason and talk together in a way that goes beyond a debate, the presenting of positions or a casual discussion.

In these sessions, it offered a way for participants to:

• build a shared understanding of an issue and its complexities;
• clarify the assumptions and values underlying different viewpoints;
• arrive at common ground that can act as the foundation for policy development, and test the common ground against real-life situations.

A dialogue guide and video were prepared for the sessions. The guide provided a primer on placebo-controlled trials (PCTs) and presented three approaches to placebo use in clinical trials. These approaches were:

1. Maximize patient protection,
2. Maximize medical knowledge
3. Maximize patient autonomy.

The sessions³ began with the video, which presented an overview on the current use of placebos in clinical trials, the policies that guide its use and the different perspectives that people hold about the future use of PCTs. Participants then asked questions of resource people who attended the sessions. Following this, participants engaged in a two-hour dialogue based on the guide. In the afternoon, they developed their common ground based on the morning's dialogue. They tested their common ground against three real-life scenarios. Participants finished the session by offering final reflections on their common ground; modifying it as they felt was appropriate.

   1.2. Synthesis Report

This report was prepared using the reports from each of the five citizen dialogue sessions. These provided several sources of data. A note-taker was present at each session and recorded the discussions, including all perspectives raised. Participants also completed worksheets to record their reflections on the scenarios and these were compiled in the session reports. All flipcharts were recorded. A compilation of the completed evaluation forms was also included in the session reports. All comments were noted without attribution.

In this final report, an effort was made to reflect the language and expressions used by citizens during the sessions while consolidating main themes and ideas. Key findings were chosen by doing a search of the main themes that emerged consistently in the dialogue and by an analysis of the responses to the scenarios.

   1.3. Participation

Sixty-nine people participated in the dialogues. A breakdown of participation by session is provided in Appendix 2. Health Canada 's Office of Consumer and Public Involvement did the recruitment for four of the sessions. Six demographic factors were considered in recruitment: age, gender, ethnicity, education, occupation and religion.

Overall, more women than men attended the sessions; 45 women compared to 24 men. Compared to the demographics for their city, participants tended to be better educated, particularly in terms of the numbers having advanced degrees, i.e. Master or Doctorate. The age breakdown was fairly representative with the exception that there were relatively few participants in the 15-24 age bracket. These latter two findings are perhaps not surprising given the dialogue topic.

The number of people from visible minorities was about half the number that would have been expected based on demographics. On average, about one-third to one-half of participants in each session had participated in a clinical trial at some time or knew a close associate who had.

   1.4. Key Findings

For many participants, a discussion on clinical trials was new; let alone on placebo-controlled trials (PCTs). Thus, there was much to learn on the current reality of clinical trials. Some of the concerns raised and recommendations made apply to both clinical trials and PCTs. For example, a number of participants had concerns about the current system of informed consent. This included a call for all clinical trial participants to know the results of their trials and the arm of the trial that they were in, e.g. receiving a placebo or experimental treatment. Informed consent is a crucial underpinning of all clinical trials, not just PCTs. However, ensuring a high standard in terms of the informed consent process was often a consideration in determining whether a PCT was appropriate or not. Thus participants' concerns about clinical trials were not unrelated to those around PCTs.

      1.4.1. A Role for Placebo-Controlled Trials

Participants clearly supported the use of placebos and PCTs as an important tool in medical research and advancement. They felt it was a necessary and valid part of developing and testing new treatments. However, it is also important to note that this support of PCTs was conditional. People said the PCTs had to be scientifically-justified; there had to be an appropriate process in place for informed consent and potential conflicts of interests needed to be minimized.

      1.4.2. Selective Use of PCTs

While the role of PCTs for medical research was affirmed, participants felt their use should be selective. In particular, it would appear that the use of PCTs became less appropriate as the perceived seriousness of the condition being treated increased. This seemed to be based on an assessment of perceived risk for the trial patients. For example, as evidenced by participants' responses to the first scenario, they were very open to the use of PCTs when the condition or ailment the treatment is designed for is a relatively minor one. This was true even if there was an existing treatment available.

Another consistent factor in the determination of the appropriateness of PCTs was the perceived vulnerability of patients. This was related to the medical risk but also included concerns about a person's vulnerability to persuasion and her/his capacity to judge clearly whether to participate in a PCT or not. This concern was raised most clearly in Scenario 3, which looked at treatment for a mental illness. In cases of vulnerability, participants often looked to patient advocacy groups to play a mediation or ombudsman role.

      1.4.3. Integration of the Three Approaches

In the dialogue guide, there were three approaches proposed for the appropriate use of placebos in clinical trials. These were:

Approach 1: Maximize Patient Protection
Some people say that experts need to determine when it is acceptable to withhold treatment from a patient in order for them to participate in a PCT. They say that PCTs should be strictly regulated in Canada and when proven treatment exists, only be allowed under very restricted conditions.

Approach 2: Maximize Medical Knowledge
Some people say that PCTs can give essential information about the safety and efficacy of new drugs and are ethical when the rights, safety and well-being of participants can be assured. They should be offered to appropriate patients whenever they are scientifically needed and do not pose an undue risk.

Approach 3: Maximize Patient Autonomy
Some people say that the current system of regulating placebo-use is paternalistic. Patients don't have the opportunity to make their own choices about being involved in PCTs and potentially having early access to experimental drugs. These people say that patients should have more leeway to determine for themselves when they wish to participate in a PCT.

In all five sessions, participants wrestled with the principles embedded in each of these approaches. They found much of value in each. Further details are provided in later sections. Overall, participants felt that all three approaches needed to be integrated into a policy and practise on appropriate placebo use.

However, as a direction for the future, participants recommended that more emphasis should be put on patient autonomy. As one session commented, "The two existing policies both need to be moderated towards a more patient-centred approach."

That does not mean that all sessions put patient autonomy as the highest priority. Even for the two sessions that did, nuances of how the three principles needed to work together were appreciated. For example, two sessions said that patient autonomy should not jeopardize the quality of the research results. However, even in this case, people felt that the principle of autonomy could be enhanced through the greater involvement of patients and citizens on Research Ethics Boards.

      1.4.4. A Trustworthy System

People called for a system that was accountable and trustworthy. They were concerned that the current system of regulating PCTs left room for numerous conflicts of interest, which might mean that the interests of patients would not come first. For example, there was concern about whether a doctor who is also a researcher in a particular PCT could give a patient unbiased advice about whether to participate in that particular PCT or not. Participants called for a system that minimizes potential conflicts of interest and that makes conflicts of interest explicit when they do occur, recognizing that it may be impossible to eliminate them all.

      1.4.5. Patient Autonomy

While patient autonomy was not the highest priority in all sessions, all did conclude that it needed to be much more strongly reflected in decisions about appropriate placebo use. As one session commented, "Patient autonomy needs to be a first consideration."

Embedded in this concept of patient autonomy were the ideas of patient as partner and patient choice. Patients should be given the choice, whenever possible, to participate in PCTs and they should be treated as partners in the process.

As noted above, assessment of risk and vulnerability altered the rating given to autonomy as the highest principle. As one participant suggested, "Autonomy is on a sliding scale of risk". As potential risk increases, other considerations such as patient protection became a higher priority. Participants saw Research Ethics Boards as being crucial players in helping to set the framework for patient autonomy and modelling the principle through a greater inclusion of patients and citizens on these Boards.

      1.4.6. Patient Protection

Patient protection was considered to be important and in one session was the central consideration. However, even in this case, the participants called for the principle to be implemented with rigour but not without flexibility. In a second session, participants agreed that the crucial factor was to have a system of checks and balances in place that work to protect a patient. A third session reinterpreted patient protection to be a focus on patient health. Participants suggested this focus might reduce the possible paternalistic interpretation of the protection principle.

A premise of the protection approach is that withholding proven treatment, as may happen in a PCT, is a violation of the duty of care. This notion, a cornerstone of health professions, is that a professional should put patients' best interests first and foremost. Certainly, participants did not debate that a doctor should put a patient's interests first. (Indeed there was a consistent concern that the total system of PCTs and clinical trials needed to minimize possible conflicts of interest at all levels.) However most felt that asking a patient if they wanted to participate in a PCT was not a violation of the duty of care. Indeed, in response to scenarios that looked at this issue, several participants commented that the question is not whether it is OK for the doctor to ask the patient. The question is whether the doctor has the right not to ask the patient if she/he wishes to participate. This comment underscores the tension that exists between an emphasis on patient autonomy and "informed choice" and one on patient protection.

      1.4.7. Rigorous Science within an International Context

There is no doubt that participants highly valued the advancement of medical knowledge. For many, the need to ensure that research was scientifically rigorous was a foundation for all the PCT work. As participants in one session commented, "If the trial is not scientifically sound, it is not ethical." Thus people suggested for example, that patient choice to participate in a PCT should not jeopardize the quality of research and the validity of results.

Participants also valued the international dimension of research. They supported the idea of Canada being a leader in medical knowledge and accepted that there may be some risks involved in doing this. They did not want Canada to potentially miss out on new drugs or treatments and were concerned this could happen if the Canadian system did not allow for many PCTs. They appreciated the need for Canada's policies and guidelines to be harmonized with the international standards, as long as that did not mean that Canada weakened its standards. In other words, Canada's policies should not fall to meet the potentially lowest common denominator acceptable to the international community.

      1.4.8. Access to New Drugs

One reason for the strong support of research was the opportunity to benefit from new drugs and treatments. Having early access to new drugs was a major selling point. If the system cannot truly provide this, people's support for the approach of Maximizing Medical Knowledge may well weaken. While this issue of access to new drugs is pertinent for all clinical trials, it was an important weighting in the trade-offs people were making in determining appropriate placebo use. It was of concern to people for example, that patients who had participated in a PCT may not have access to an experimental drug that had been of benefit to them, once the trial was over.

      1.4.9. The Role of Research Ethics Boards

It is clear from these dialogues that Research Ethics Boards are not well known by the Canadian public. Their role and composition was not evident to the majority of participants. This being the case, some of the suggestions participants made about Research Ethics Boards may already be the status quo. In general, they saw Research Ethics Boards as playing a crucial role in:

1. ensuring a valid, objective process in considering PCTs,
2. providing some of the checks and balances required in the system,
3. safeguarding patient rights, e.g. ensuring that informed consent is respected, and that there is full disclosure about the PCT and its results.

It was also clear that at low to medium levels of vulnerability-risk (as expressed in Scenarios 1 and 2), participants expected Research Ethics Boards to uphold the principle of patient autonomy as the first consideration. They should ensure that PCTs are being run well, that the rules are being followed and that patients have the information they need to make their own decisions about participating. Research Ethics Boards should not be screening out PCTs at low to medium levels of risk, as could happen in a patient protection approach.

Participants were very surprised to find out that there is currently little consistency in the decisions made by Research Ethics Boards. They were concerned that in some parts of the country, Research Ethics Boards may act more restrictively in terms of patient choice than in other parts. Thus a person living in one area may have less opportunity to participate in a PCT because the Research Ethics Board for their hospital or region is stringently applying a Patient Protection approach. Or the reverse could be true - risk may be under-assessed by one Research Ethics Board. People were also concerned that not all Research Ethics Boards use the same policy to guide their decision-making or interpret it consistently.

A clear recommendation from all the sessions was for much greater consistency across Research Ethics Boards. While participants recognized that this is an issue for all clinical trials, they also considered it to be a crucial factor in determining appropriate placebo use in Canada. Consistency is essential in ensuring an accountable and trustworthy system. Participants appreciated that, even with increased consistency, a Research Ethics Board in one area may still make a different decision in one hospital than another. This may be for very practical reasons, e.g. no capacity for another trial in their hospital. For this reason, participants felt that it was important that information on the decisions made by Research Ethics Boards, including their reasons for a particular decision, be disclosed and accessible.

A second clear recommendation was that Research Ethics Boards⁴ should have more patient and/or citizen representation. In addition, their participation should be seen as crucial, not token. This may mean providing appropriate education and information to patient/citizen representatives to ensure they can more fully participate in the discussions.

   1.5. Learning from the Scenarios

The three scenarios that were developed for the dialogue sessions were constructed to test out areas of concern to the National Placebo Working Committee. In all three scenarios, effective treatment ⁵ was available. (Among professionals, there is already an acceptance of PCT use in situations for which no effective treatment exists. The controversy begins in situations where there is already a proven treatment.) The first scenario involved a minor ailment (acne) for which current treatment was effective but with some side effects. The second scenario presented an ailment (high blood pressure) that over time could have serious effects, but that for the time of a PCT was of relatively low risk. The third scenario explored a higher risk ailment (depression), which involved psychological discomfort and/or pain.

Based on these scenarios, the following directions for a placebo policy were given by participants:

1. In cases of a minor ailment, patient autonomy is paramount and patients should be given the choice to participate or not. Research Ethics Boards should not be screening out PCTs at this level, even if proven treatment already exists. They should work to ensure that patients have the information they need to make an informed decision to participate or not. It is acceptable for physicians to ask patients if they wish to participate even if it means coming off current medication for the time of the trial.

2. In cases where the health risk is low for the duration of the trial, PCTs were seen as appropriate. Patients should be given the choice, based on good information, as to whether they want to participate or not. Even in cases where the PCT was testing a "me-too" drug (which means it is similar to a drug already on the market), participants still supported PCT use, but by a smaller majority than with Scenario 1. For some the fact that the drug may only offer marginal improvement meant that the possible added risk of a PCT was no longer acceptable. Others felt that patients should have the right to choose for themselves, as what is marginal improvement for some might be significant for others.

3. In cases where the risk was judged to be higher and psychological pain was involved, the majority felt that PCTs were not appropriate if alternative types of trials were available, e.g. Active Control Trials⁶ (ACTs.) For many participants, the illness given in Scenario 3 was seen as life-threatening, due to a possible risk of suicide. Thus as one group said, "In life-threatening situations, patient protection comes first. Severe discomfort or pain is not acceptable." The groups were split about whether it was acceptable for newly diagnosed patients, e.g. those not yet receiving any medication, to be asked to participate in a PCT.

   1.6. Evaluation

At the end of each session, participants were asked to complete an evaluation form. The results were very positive for all assessed components of the sessions, with the average ratings on all questions being above four on a five-point scale. People found the resources prepared for the sessions - the dialogue guide and the video - to have been useful, easy to understand and informative. They felt that people had been able to share their perspectives in a collaborative way and most said they would like to participate in another dialogue session. Most also said that, as a result of the session, they were more knowledgeable about PCTs and the factors that need to be considered in assessing their use.

Participants stated that they found deliberative dialogue to have been a very useful way to address complex issues. Most felt that, collectively, they had provided insights and information that will be useful for determining appropriate placebo use in clinical trials in Canada. A number mentioned having a greater sense of confidence and trust in Health Canada and CIHR after having been through the session. This seemed to be both because they now knew more about what these bodies do and because they felt there was an openness to listen to and truly consider the input of citizens.

   1.7. Conclusion

The dialogue sessions were designed to provide input for determining appropriate placebo use in clinical trials in Canada. In particular, the process was designed to get citizens' perspectives on some of the controversial issues in the professional debate on placebo use in Canada today. Based on these five dialogues, the following summary of participants' views is offered:

1. PCTs are valuable and an acceptable part of advancing medical knowledge.
2. Research using PCTs must be valid and justifiable.
3. A patient-centered approach needs to be fostered.
4. Patient autonomy (choice) should be more strongly reflected in decisions about appropriate placebo use and take clear precedence in cases of low to medium risk.
5. Patient protection (or health) may need to trump patient autonomy at higher levels of risk and/ or patient vulnerability. Interpreting when this needs to happen requires more patient and citizen participation on Research Ethics Boards.
6. PCTs can be acceptable even when alternative proven treatments are available.
7. PCTs can be acceptable even if the treatment to be tested is a me-too drug.
8. There needs to be greater consistency and transparency in the decision-making of Research Ethics Boards across the country.

The appropriate use of placebos in clinical trials in Canada was not an easy topic for participants to dialogue on. It is complex and the controversy surrounding PCTs has both components of science and ethics. However, participants in every session were able to reach important elements of common ground that could provide direction for placebo use in clinical trials in Canada.

2. Alternative Feedback Guide

The Public Involvement Coordinating Committee (PICC) developed the Alternative Feedback Guide to the Appropriate Use of Placebos in Clinical Trials to give an opportunity for Canadians who could not attend the dialogue sessions to provide input. The electronic tool is a modified version of the dialogue guide booklet developed for the citizen dialogue sessions. The content of the electronic document (also available in print) was very similar to the dialogue guide, except for a few additions to help frame the process for individual respondents. Additions such as a Question and Answer section at the beginning of the text were provided to help respondents go through the document without the benefits of face-to-face explanations on the complex issues of placebo use in clinical trials. Contact information for regional Office of Consumer and Public Involvement (OCAPI) staff was provided. They could answer any questions (by email or phone) the respondents may have.

Respondents were asked to answer questions on the three different approaches presented in the guide. Unlike the face-to-face meetings, questions on the scenarios were optional. All related documentation was available on the website.

   2.1. Participation

A total of 35 individuals⁷ completed the Alternative Feedback Guide. The majority of respondents were from the Toronto and Manitoba/Saskatchewan areas, which had been specifically targeted. From Toronto, most of the respondents had originally been selected to participate in a face-to-face dialogue in Toronto, which was cancelled due to the SARS outbreak in that city. Manitoba/Saskatchewan was targeted because it had not been possible to hold a face-to-face dialogue session in these provinces. Most respondents sent in their feedback via email. Two individuals who responded on the web mentioned some difficulty in sending back the replies.

   2.2. Key Findings

Respondents appreciated aspects of all three approaches. In particular, they valued:

• Patient autonomy for decision-making regarding their personal situation. This included a strong emphasis on access to high quality information to help patients make decisions about being involved in trials.
• Safeguards to ensure the safety of the PCT participants. This included a system of regulation and approval that is consistent across the country. The role of Research Ethics Boards was seen as important in this respect. Respondents said they needed to have adequate resources and training to do their job.
• Quicker access to new medication within a regulated framework for PCTs. A strong research community participating in international studies was seen as key. However the advancement of medical knowledge should not overshadow the patients' welfare.

While patient autonomy was considered to be a fundamental principle, respondents were cautious as to how the principle could be operationalized. In particular they were concerned that patient autonomy may put too much pressure on some patients. They suggested that some might not understand the risks involved. There is room for error or manipulation due a patient's sickness, lack of knowledge, desperation etc. In addition, respondents commented that patient autonomy should not compromise good science.

The scenarios gave a chance for respondents to think about the application of their views on PCTs. As the questionnaire took most people more than 75 minutes to complete, the number completing this optional section dropped to 22. However there are interesting and consistent findings from the first two scenarios. These are:

1. For a minor condition, it is considered acceptable to ask a patient to stop their current medication to try an experimental treatment, as long as it is the patient's decision and the patient is closely monitored while on the trial.
2. Research Ethics Boards should not screen out PCTs involving minor conditions or discomfort, on this basis alone.
3. It is appropriate to ask a patient to consider participating in a PCT even when effective treatment is available, if the patient has the option to make his or her own decision about participating, after being well-informed of the possible risks involved.
4. It is considered acceptable to use PCTs when the medication being tested is a me-too drug.

Sixteen people responded to Scenario 3. They were divided in terms of whether it is appropriate to use PCTs to test treatments for conditions involving psychological discomfort or pain. On the issue of whether Active Control Trials were better to use than PCTs, most indicated that PCTs were preferable as they involved less people and were more manageable.

   2.3. Evaluation

The subject was of great interest to the respondents. Most mentioned they had learnt a great deal going through the documentation and were now more aware of the issues surrounding placebo use in clinical trials. They were pleased that they could contribute to the process. As one person said, "It is nice to be asked".

In general, the responses on the evaluation form were lower (between 3 and 4 on a five point scale) than in the face-to-face dialogue sessions. However, the evaluations still indicate that most people found the process informative and felt that their input would be useful to Health Canada and the Canadian Institutes of Health Research. Most people indicated that it took them more than 75 minutes to complete the questionnaire, but this was not considered to be unreasonable.

Appendix 1: Sample Agenda for the Dialogue Sessions

Health Canada and the Canadian Institutes of Health Research
The Appropriate Use of Placebos in Clinical Trials
Public Consultations, March 2003

9:00 - 9:30	Welcome and introductions
9:30 - 10:00	Video presentation and discussion
10:00 - 10:30	Introduction to deliberative dialogue
10:30 - 10:45	Break
10:45 - 12:30	Deliberative dialogue using the dialogue guide
12:30 - 1:15	Lunch
1:15 - 2:00	Exploring common ground
2:00 - 2:30	Scenario 1
2:30 - 2:45	Break
2:45 - 3:15	Scenario 2
3:15 - 4:00	Scenario 3
4:00 - 4:30	Wrap-up and evaluation

Appendix 2: Participant Chart for the Dialogue Sessions

Session	Date	# of Participants	Gender	Age	Education
Edmonton	March 15	15	6 M 9 F	0 (15-24) 2 (25-44) 3 (45-54) 3 (55-64) 7 (65 +)	Community College: 1 Baccalaureate: 6 Postgraduate: 8
Vancouver	March 16	17	6 M 11 F	2 (15-24) 9 (25-44) 0 (45-54) 4 (55-64) 2 (65 +)	HS students: 2 HS graduates: 3 Community Coll.: 3 Baccalaureate: 6 Postgraduate: 3
Halifax	March 22	10	2 M 8 F	0 (15-24) 3 (25-44) 3 (45-54) 2 (55-64) 2 (65 +)	HS: 1 College: 2 Baccalaureate: 2 Postgraduate: 5
Montreal	March 23	10	3 M 7 F	0 (15-24) 2 (25-44) 3 (45-54) 2 (55-64) 3 (65 +)	No diploma: 1 College: 3 Baccalaureate: 5 Postgraduate: 1
Ottawa	May 10	17	7 M 10 F	1 (15-24) 4 (25-44) 5 (45-54) 5 (55-64) 2 (65 +)	High School: 4 College: 3 Baccalaureate: 8 Postgraduate: 2

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¹Placebo-controlled trials (PCTs) are studies in which a placebo is given to one group of participants, while the drug being tested is given to another group.

²Consultations with other stakeholders are also being held. There was a multi-stakeholder conference in March 2002. An electronic consultation with stakeholders is planned to begin in November, 2003. For more information on these consultations or the work the NPWC, visit the CIHR Web site.

³The agenda is provided in Appendix 1.

⁴Currently all Research Ethics Board must have at least one community representative.

⁵Proven or effective treatment: Drug or therapy previously proven to be effective and safe for a patient's condition.

⁶An active control trial is a clinical trial where an experimental drug is compared against a drug that is already available on the market.

⁷There were also a number of people who did not complete the Alternative Feedback Guide, but used the opportunity of the website to express concerns or raise issues about PCTs. All such comments were sent to the National Placebo Working Committee.