GlaxoSmithKline (GSK) Response to World Health Organization International Clinical Trials Registry Platform (ICTRP) Consultation September 2005

Transcription

1 GlaxoSmithKline (GSK) Response to World Health Organization International Clinical Trials Registry Platform (ICTRP) Consultation September 2005 Introduction GlaxoSmithKline (GSK) is committed to enhancing transparency of clinical trial information. In September 2004 we launched the GSK Clinical Trial Register which currently contains over 1000 study summaries of completed clinical trials of marketed medicines. In addition we recognise that publicly available internet-based registration of ongoing clinical trials can provide a stimulus for increased participation in clinical research. It also provides an important reference point to track the subsequent disclosure of clinical trial results. We have therefore committed to posting all patients trials initiated on or after November 1 st 2004 to clinicaltrials.gov using the minimum data set identified in the report from the World Health Organization (WHO) Technical Consultation on Clinical Trials Registration Standards Meeting (25-27 April 2005). In keeping with the report from this meeting, one or more of the following fields may be regarded as sensitive for competitive reasons and the release of the information delayed: primary outcome; key secondary outcomes; intervention; target sample size; and official scientific title of the study. This information will be disclosed, at the latest, after the drug is first approved in any country for the indication being studied. We therefore welcome the opportunity to provide comments on: WHO Registration Data Set Unique ID Assignment Register Certification Key Points WHO Registration Data Set (see also detailed comments in the table) We note that the terminology used in the proposed WHO Registration Data Set differs from that agreed at the WHO April meeting. To avoid confusion and ensure consistency, we urge WHO to use the terminology agreed for the minimal data set at the World Health Organization (WHO) Technical Consultation on Clinical Trials Registration Standards Meeting (25-27 April 2005). This terminology is also used by the International Committee of Medical Journal Editors (ICMJE) 1 1 Is This Clinical Trial Fully Registered? A Statement From the International Committee of Medical Journal Editors JAMA, June 15, 2005 Vol 293, No. 23

2 While we consider proposals to use controlled vocabularies for trial registration have merit, there are a number of practical issues to be overcome (e.g. where there is no generic name for the investigational medicine or where the primary outcome is unprecedented). In addition agreement would be needed on the vocabulary to be used and this would need to be implemented in all primary registers. Resolution of these issues is likely delay the WHO Platform. We suggest that WHO build the Platform using the minimal data set agreed at the WHO meeting in April and consider enhancements on an ongoing basis once the platform is up and running. A number of data elements include additional information to that agreed at the WHO meeting in April. For example, contact information for funding sources and the inclusion of ethics committee ID numbers. It is of vital importance that the information essential to meeting the primary objectives of trial registration are included while not unnecessarily distracting trial sponsors and/or consuming additional resources. We consider the additional information unnecessary. Unique ID Assignment The diagrams to illustrate the process of assigning a WHO Clinical Trial Unique ID (WHO CT UID) are, without explanation, extremely difficult to follow. Nonetheless, the need for a WHO CT UID as an additional number has not been demonstrated and the process appears to risk delay of registration of trials. The number assigned by the primary register (e.g. clinicaltrials.gov) can adequately serve as the unique clinical trial number for registration purposes. We are also opposed to WHO assigning a WHO CT UID because an additional number risks causing considerable confusion. We are opposed to the proposal for ethics committees/irbs to approve the WHO Registration Data set. Requiring an ethics committee/ IRB to confirm registration is outside of their normal remit, and could place an additional burden on already overburdened ethics committees/irbs which could lead to additional expense and occasional delay in approval and initiation of clinical trials, a result that would run counter to stakeholder interests. As an alternative the sponsors of primary registers should have a mechanism in place to spot-check records against the trial protocol. We do not support proposals to register trials before ethics committee/irb approval because it does not aid patient enrollment or increase the ability to track the subsequent disclosure of clinical trial results. Sponsors have an obligation to devote resources to promptly complete the registration of clinical trials. However the resources required to continually update information on clinical trial registers because of changes agreed with ethics committees/irbs could be considerable. A requirement to register clinical trials prior to IRB approval (i.e., before their initiation) is likely to result in more changes to records than if registration took place at the start of patient

3 enrollment. Importantly, registration before IRB approval does not align with providing patients with the opportunity of participation as at this time the trial s location is not established and the trial is not open to recruitment. Furthermore, given the diverse and complex nature of how Ethics Committees/IRBs around the world are governed and operate, gaining agreement to changes to their remit is likely to be particularly challenging (eg may require legislative change) and may unnecessarily delay this WHO initiative. We do not support the requirement to use the WHO unique identification number on informed consent documents. This is not practical as the number will be assigned after the informed consent documents have been reviewed by ethics committees/irbs and inclusion of such a number is likely to delay finalization of informed consent documents and recruitment of patients. Moreover the benefit of including such a number on informed consent documents is not apparent. Register Certification Reference is made to an escrow mechanism as the mechanism to delay certain data elements. However the WHO meeting in April did not agree such a mechanism and concluded that WHO will convene a group to develop to develop a mechanism. This should therefore be removed from the register certification requirements.

4 . GSK Comments on WHO Registration Data Set Old Name Item Definition/Explanation GlaxoSmithKline Comments Field Value New Name Unique trial number Trial registration date Register and Trial ID # Date of Registration in Register Select Certified Register Trial ID # Secondary IDs Other Trial ID#s Issuing Authority Select name of Certified Register submitting the CT-UID request (the trial's " Register"), and that register's registryspecific unique ID assigned to this trial. 1 Jan Date when initial WHO Registration Data Set was submitted to the Register DD/MM/YYY. ID Number Click to add more Other identifying numbers and issuing authorities besides the Register. Include at least the name and trial ID# from: the Research Ethics Board of the main study site, and all other certified and noncertified trial registries that have issued a number to this trial. Other ID numbers (e.g., sponsor name and number, funding agency and grant number) may also be submitted. There is no limit on the number of Other Trial ID numbers that can be provided. The need for a WHO CT-UID has not been demonstrated. The primary register ID number can be used for registration purposes. Agree with the definition. This should be established by the Register as described by ICMJE The old name Secondary IDs should be retained. This is the term agreed at the WHO meeting in April and is the term used in the ICMJE criteria. The Research Ethics Board identification number should not be a required secondary ID: 1. The purpose of this number is for the Ethics Research Board to identify the trial in correspondence 2. Not all Ethics Research Boards use a number. Some ethics committees identify the study by an abbreviated title 3. For trial registration/search purposes the Register s

5 unique ID number is sufficient 4. For multicentre multinational trials there will be many Ethics Boards and Ethics Board ID numbers. Posting all this information is not necessary may cause confusion, and will be a significant resource burden. We agree with the ICJME definition: May be assigned by sponsors or other interested parties (there may be none) Clinicaltrials.gov also notes that there may be none 4. Funding source(s) Funding Source(s) Name Address or Contact Information Source(s) of monetary support for the trial (e.g., funding agency, foundation, company). It is not necessary to provide the address or contact information for funding sources. This information is not relevant to the objectives of trial registration and if needed could be obtained from the research contact. Click to add more The ICMJE criteria do not include Address or Contact Information and should be deleted. 5. sponsor Sponsor Name Address or Contact Information The individual, organisation, group or other legal person taking on responsibility for securing the arrangements to initiate, manage and finance a study (including arrangements to ensure that the design of the study meets appropriate standards and to ensure appropriate conduct and reporting). The primary sponsor is normally the main applicant for regulatory authorisation to begin the study. It may or may not be the main funder. It is not necessary to provide the address or contact information for the primary sponsor. This information is not relevant to for the objectives of trial registration and if necessary could be obtained from the research contact. The ICMJE criteria do not include Address or Contact Information

6 6. Secondary sponsor(s) Secondary Sponsor(s) Name Address or Contact Information Click to add more Additional individual, organisation or other legal person that has agreed with the primary sponsor to take on responsibilities of sponsorship. A secondary sponsor may have agreed o o o to take on all the responsibilities of sponsorship jointly with the primary sponsor; or to form a group with the primary sponsor in which the responsibilities of sponsorship are allocated among the members of the group; or to act as the sponsor s legal representative in relation to some or all of the trial sites. The definition should include the term if any as there may not be any secondary sponsors. It is not necessary to provide the address or contact information for the secondary sponsor. This information is not relevant to for the objectives of trial registration and if necessary could be obtained from the research contact. The ICMJE criteria do not include Address or Contact Information. 7. Responsible contact person Contact Person address address of the person who will respond to queries from the public The old name responsible contact person should be retained. This is the term agreed at the WHO meeting in April and is the term used in the ICMJE criteria Agree with this definition. However an address or telephone contact number should be permitted. A name should not be required. 8. Reseach Contact Person Lead Principal Investigator Name Affiliation Name and affiliation of the person with legal and scientific responsibility for the trial. For a multi-center study, enter the lead Principal Investigator. The old name research contact person should be retained. This is the term agreed at the WHO meeting in April and is the term used in the ICMJE criteria The research contact may or may not be the lead principle investigator. It may be a contact within the sponsor s organisation. In addition the name of the person should not be required. An address or

7 telephone contact number should be permitted. We agree with the ICMJE definition: Person to contact for scientific inquiries about the trial Title of the study Official scientific title of the study Public Title Protocol title intended for the lay public. The old name title of the study should be retained. This is the term agreed at the WHO meeting in April and is the term used in the ICMJE criteria. Scientific Title Scientific title, including the intervention name, condition, and primary outcome. Example: "A Randomized Controlled Trial of Chocolate on Beck Depression Scores in Patients with Seasonal Affective Disorder" Agree with this definition. The definition should align with the ICMJE criteria which states that this can be omitted if the researchers wish. The old name official scientific title of the study should be retained. This is the term agreed at the WHO meeting in April and is the term used in the ICMJE criteria Scientific titles should include the intervention name and condition. However there should not be a requirement to include the primary outcome of the study (in terms of the measurement used). This information is provided separately and need not be included in detail in the trial title. We regard the ICMJE definition to be more pragmatic: This title must include the name of the intervention, the condition being studied, and the outcome (eg, The

8 International Study of Digoxin and Death from Congestive Heart Failure) The definition should make it clear that registration of this field may be delayed for competitive reasons as agreed at the WHO meeting in April. 11. Research ethics review Research Ethics Board Approval Yes Whether or not this trial has received final research ethics board approval at the time that the CT-UID was requested. The old name research ethics review should be retained. This is the term agreed at the WHO meeting in April and is the term used in the ICMJE criteria. To ensure trials are registered in a timely fashion, this definition should be Whether or not this trial has received at least one research ethics board approval. 12. Condition Disease or Condition Studied Controlled Term 1 Click to add more disease(s) or condition(s) studied (e.g., depression, breast cancer). Select the appropriate controlled vocabulary term. Agree with the definition. However use of a controlled vocabulary term requires further detail as to the vocabulary to be used and the agreed use of these terms in all primary registers. This is not a requirement for ICMJE and was not agreed or discussed at the WHO meeting in April. 13. Intervention(s) Intervention(s) Intervention name Controlled Term 1 Duration, other details The specific name of the intervention(s) being studied, selecting the generic name where applicable (e.g., zidovudine, self'- hypnotic relaxation) from the controlled vocabulary. For multi-armed studies, the intervention(s) for each arm should be Intervention names should be provided. However the use of controlled vocabulary terms may not be practical as some interventions may have only have a compound number and the controlled

9 Click to add more interventions described. If an active control is used, be sure to enter in the name(s) as well. For each intervention, describe other intervention details (duration, mode of administration, etc) vocabulary would need to be regularly updated. This may delay registration of trials. We agree with the ICMJE definition and suggest this is used. A description of the study and comparison/control intervention(s) (for a drug or other product registered for public sale anywhere in the world, this is the generic name; for an unregistered drug the generic name or company serial number is acceptable). The duration of the intervention(s) must be specified. The definition should make it clear that registration of this field may be delayed for competitive reasons as agreed at the WHO meeting in April. 14. Key inclusion and exclusion criteria Inclusion and Exclusion Criteria Eligibility criteria for participant selection, including age and gender criteria. Be sure to include all clinically relevant criteria. The old name key inclusion and exclusion criteria should be retained. This was agreed at the WHO meeting in April and is the term used by the ICJME. This enables important information to be registered while not providing the detail which is not relevant to meet the objectives of trial registration. 15. Study type Study type Randomized? Controlled? Yes Yes A trial is "randomized" if participants are/were assigned to intervention groups by chance. A trial is not randomized if participants are/were expressly assigned to intervention groups. A trial is "controlled" if participants can/could have been assigned to receive a Agree with the definition

10 16. Anticipated trial start date Date of First Enrollment placebo, an active control, or a dose comparison, or a historical control will be/was used. 1 Jan Estimated date of enrollment of the first participant if trial has not yet started recruitment, or the actual date of first enrollment if the first participant has already been enrolled (DD/MM/YYYY). Agree with the definition 17. Target sample size Target Sample Size Number of participants that this trial plans to or had planned to enroll. Agree with the definition. The definition should make it clear that registration of this field may be delayed for competitive reasons as agreed at the WHO meeting in April. 18. Recruitment status Recruitment Status at Time of CT-UID Request Not yet recruiting Recruitment status of this trial at the time that the CT-UID was requested. o Not yet recruiting: participants are not yet being recruited or enrolled o Recruiting: participants are currently being recruited and enrolled o No longer recruiting: participants are no longer being recruited or enrolled o Completed: participants are no longer being recruited; data analysis is complete o Suspended: recruiting or enrolling participants has halted but potentially will resume o Terminated: recruiting or enrolling participants has halted and will not resume This definition should align with the ICMJE definition: Is this information available (yes/no) (if yes, link to information). 19. outcome Outcome(s) Outcome Name Controlled Term 1 Timepoints Outcomes are specific measurements or observations used to measure the effect of experimental variables in a study. The Outcomes are the specific measures that will be used to determine the The use of controlled terms could be problematic where the sponsor has developed a novel endpoint/outcome for the trial. This risks delaying registration of the trial. This is not a

11 Click to add more effect of the intervention(s). Select the controlled vocabulary term for each and every primary outcome of the trial. Also provide all the timepoints at which each outcome is to be measured. Examples: Outcome Name: all cause mortality, Timepoints: one year; Outcome Name: score on a depression rating scale, Timepoint: 6,12, and 18 weeks requirement for ICMJE and was not agreed or discussed at the WHO meeting in April. The definition should make it clear that registration of this field may be delayed for competitive reasons as agreed at the WHO meeting in April. 20. Key secondary outcomes Secondary Outcomes Outcome Name Controlled Term 1 Timepoints Click to add more Outcomes are specific measurements or observations used to measure the effect of experimental variables in a study. Secondary outcomes are measures other than the primary outcomes that will be used to evaluate the intervention(s), and that are specified in the study protocol. Select the controlled vocabulary term for each secondary outcome of the trial. Also provide all the timepoints at which each outcome is to be measured. Examples: Outcome Name: cardiovascular mortality, Timepoint: 6 months; Outcome Name: functional status, Timepoint: 4 and 8 weeks The old name key secondary outcomes- should be retained. This was agreed at the WHO meeting in April Providing all secondary outcomes is not necessary to meet the objectives of trial registration. Time points should not be required. For some trials this information will be overly complicated for primary and key secondary outcomes. Also note that the main protocol register clinicaltrials.gov restricts the number of characters for this field. The definition should make it clear that registration of this field may be delayed for competitive reasons as agreed at the WHO meeting in April.