Presentation Guidelines

Request for Expedited Review:

Sponsors must request Expedited Review of their clinical trial or projects through Consortium Headquarters. In return, CUOG Headquarters will:

Issue a letter to formally engage the Sponsor in the review process inclusive of details and financial terms. Please note that the full cost of the Expedited Review will be borne by the Sponsor requesting the review as per the letter of engagement. Make all necessary arrangements to organize the review Issue a call for Consortium Reviewers Sign a blanket confidentiality Agreement of behalf of the Consortium Provide the names and addresses of Reviewers to the Sponsor so that Sponsor can send all relevant materials (i.e. protocol, investigational brochure, related publications) directly to Reviewers, prior to the date of the review.

Review Team:

Through a centralized Call for Reviewers, the Consortium will bring together a cross section of available members, consultants and experts to form a Reviewer team lead by the Head Reviewer. Depending on the scope and scale of the project the Reviewer Team usually consists from 4-7 persons as follows:

Head Reviewer – usually a senior Clinician and a senior member of Consortium Chairman and or 1 other member of the Board of Directors 1-3 additional clinician members of the Consortium (Active or Associate) Associate Members ( as required) possessing expertise in a given area: (i.e. pre-clinical, epidemiology, statistician) External Consultant (as required) i.e. Medical specialists from other required therapeutic background (eg. radiation and medical oncologists, nephrologists, microbiologists, endocrinologists , etc.)

Expedited Review Charges:

The Sponsor requesting a CUOG Expedited Review will bear all expenses relating to the Expedited Review at cost. Charges incurred may involve some of the following: transportation, parking, accommodation, reviewer honoraria, room rental, food and beverage, teleconferencing, audio-visual, administrative on-site fee, and 20% corporate surcharge. CUOG makes every effort to keep these costs to a minimum.

Call For Sites:

A Call for Sites, is the “Go Ahead – Signal” which signifies to all CUOG investigators that the clinical trial or project has been satisfactorily reviewed, all negotiations have been completed, and the project is ready for clinical trial participation. Investigators wishing to participate in the study, are required to communicate their interest to CUOG headquarters within 10 business days. CUOG then forwards a “Short-List” of interested investigators directly to the Sponsor. The final selection of sites is made entirely at the Sponsor’s discretion.

General Information:

1 On – Site and Teleconference reviews generally last approximately 2-3 hours and cover experimental and clinical data.

2 It is the responsibility of the Sponsor to send the protocol and all presentation materials directly to all reviewers well before the date of review.

3 All Reviewers must receive the protocol and presentation materials prior to the review date. The entire review team, under the direction of the head reviewer, will be responsible for creating the FIRST draft of the reviewer assessment report (RAP). A copy of this first draft review will be sent to all reviewers and the sponsor just before the actual review occurs. It is desirable for the SECOND draft of RAP to be completed before the review meeting ends, since the Sponsor will anticipate a finalized report within 15 business days.

4 All Reviewers will receive Evaluation Forms to write down their comments. At the end of the meeting, completed Evaluation Forms must be sent directly to the head reviewer with a copy to Consortium Headquarters. Following the review, if evaluation forms are not fully completed, then they must be faxed or emailed to the both the Head Reviewer with a copy to Consortium Headquarters ASAP.

5 Agenda: In brief the Sponsor will meet with Consortium Reviewers for approximately 1.5 hours, the Reviewers will then confer privately for approximately 30 minutes, then invite the Sponsor back for a further 30 minute question period and wrap up. A FINAL AGENDA WILL BE SENT OUT PRIOR TO THE REVIEW.

6 As stated above, following the review meeting, all Reviewer Evaluation Forms must be sent to the Head Reviewer immediately after the review so that the final assessment report can be prepared. The Head reviewer will send a composite (DRAFT) report to all reviewers following the review meeting via fax or email. The Head reviewer is responsible for producing a finalized assessment report by editing the document based on the final reviewer comments. All reviewers will be expected to comment on all drafts of the report in a timely manner. The head reviewer will seek final consensus from the review team to accept or reject the project, rank the project (low, medium, high) and determine whether the study should proceed through the consortium.

7 Scale of Remuneration and Charges: The Head Reviewer will receive a $3000 honorarium. All additional Reviewers will each receive a $2000 honorarium. These honorariums will be paid to reviewers from the Consortium upon completion of the Reviewer Assessment Report (RAP). The full and final cost of the review will borne by the sponsor.

8 Reviewers who have been confirmed, but who feel that they cannot accommodate these guidelines must inform Consortium Headquarters immediately, so that a replacement reviewer can be found.

Presentation Guidelines

Pharmaceutical Sponsors requesting Expedited Review of their clinical trials and projects may use the following Guidelines to structure the content of their presentation. These guidelines will assist the Reviewers in preparing Assessment Reports and also guide the Review Meeting agenda.

Acknowledging that clinical trials and projects are unique and will be reviewed at varying stages of their overall clinical or project development these guidelines should be customized meet meeting objectives.

Pharmaceutical Sponsors will be expected to assemble a presentation team of 2-5 of their scientific experts and company representatives who will be responsible to fully present all aspects the project to the Consortium Reviewers.

Pre-Clinical Presentation Guidelines:

  • State Purpose of trial and describe the rational for the use of drug:
  • Pharmacology of Study Medication
  1. Fully describe the pharmacokinetics
  2. What is the proposed dosage of the medication
  3. What is the solubility and pKa?
  4. Is there a range of efficacy? Is this dose-dependent?
  5. How is the drug metabolized?
  6. What adverse medical conditions will affect metabolism?
  7. What is the mechanism of action?
  8. Are there other medications similar to this drug? If so provide history.
  9. Provide a comparison of the advantages and disadvantages of test drug to existing other medications
  10. Describe any potential drug interactions
  11. Provide additional relevant information regarding pharmacology not covered in Section B.
  • Animal Models

What animal model(s) was used in initial trials of this drug? Why was this particular model(s) and animal(s) chosen? If more than one model was used, were results comparable? What were the doses of drug used in the model? Is the human dosage being tested comparable to the effective dosage found in the model? If not, why is the human dose equivalent, higher or lower? Has a proposed clinical effect been correlated with in vivo work? Describe the transition from animal model to human clinical trial(s). What are the long-term effects of this drug? Provided additional relevant information regarding the Model.

  • Drug Administration

Are drug effects dose-related? In what clinical scenario is this drug effective? Provide additional relevant information on drug administration.

Intravesical maintenance BCG in both arms. 50% will received ZD 1839 (Iressa) at 250mg po day x 3 years

Clinical Trial Presentation Guidelines

1 Trial Scope:

  • State purpose of the trial
  • State the intended overall sample size, and recruitment expectation from Consortia sites.
  • Describe the expected level of improvement.
  • What is the proposed overall duration of the trial? When is the study scheduled to begin or Is it currently ongoing. State expected start-up and closure dates.
  • Has a projected time line or critical path of logistical events been established? (i.e. site selection, study initiation, regulatory approval, investigator meeting, interim analysis, etc.)
  • Is the study seeking Canadian, North American or international involvement?
  • Will the study drug be provided by sponsor or does it have to be prescribed?

2 Rational for use of drug

3 Brief review of pre-clinical findings

4 Type of clinical condition/disease state

5 Randomization Procedures: Comment if the study is blinded, unblinded, double-blind etc., and describe the randomization strategy.

6 Clinical Update:

  • Experience in human subjects
  • Available preliminary clinical trial(s) data
  • Placebo Group?
  • Clinical Endpoints (primary, secondary, surrogate etc.)

7 Description of inclusion / exclusion criteria

8 Dosing:

  • Single Dose vs. Dose-ranging
  • Method of drug administration (e.g. oral, continuous or intermittent i.v. infusion, rectal, etc.)
  • Duration of drug administration (hours, days)?
  • Describe method of dealing with placebo group

9 Description of main side effect profile:

  • What are the serious adverse events (SAEs)?
  • What are the requirements for side effect monitoring (i.e. laboratory interventions: blood test(s) imaging, bioassay(s), etc.)?
  • If laboratory interventions, how will this affect the patient (e.g. frequency of tests, number of needle punctures etc.)

10 Initial Assessments:

  • History and Physical
  • Clinical Scales (e.g. International Prostate Symptom Score, Sexual Function Inventory Questionaire)
  • Objective Functional Assessments (Flow, PVR, etc.)
  • Diagnostic Maneuvers (Cystoscopy)
  • Imaging
  • Labs

11 Outcome Measures:

  • What? When? How often are evaluations performed?
  • Clinical scales
  • Clinical recurrence/survival
  • Imaging
  • Quality of Life Assessments

12 Describe the rationale for determining how the study is to be powered and related parameters necessary to achieve statistical significance.

13 what regulatory approvals (tpp/ fda) are needed? Are pending? Describe time line to meet regulatory approvals.

14 Safety Monitoring:
Describe Method of Safety Monitoring (composition of DSMB, internal vs. external DSMB)

15 Ethical Considerations?
Are there any known ethical consideration or anticipated barriers in obtaining local IRB approval?

16 Stopping Rules

17 Are there any proposed Add-On Studies as follows (if so will additional funding be provided)?

  • Pharmaco-economic
  • Open Label
  • Compassionate Use
  • Post-Marketing Surveillance
  • Pediatric
  • Other

18 Mandatory Site Requirements:
Describe any mandatory site requirements (i.e. specialized diagnostic equipment and specialized medical services) that are unique to this protocol.

19 Funding:

  • Is there a proposed study Budget?
  • Has the per patient cost been identified?
  • All Consortium sites will receive the same per case funding and overall study budget.
  • All Consortia investigators will receive individual clinical trial payments either directly from Sponsor or c/o the Consortium. The Consortium will work with the Sponsor to determine the optimal study budget. In addition to the per patient cost, the study budget must allow for pass through start-up fees, and a fixed administrative institutional/professional overhead

20 Disclosure of Study Results:
The Consortium acknowledges that all study data, in the context of the clinical trial or project, is owned by the Sponsor, but strongly recommends that, any study results, regardless of positive or negative outcome, be made available to the public. Ideally Sponsor should at their discretion agree to select an appropriate medium to disclose study results, including but not limited to, investigator meetings, published abstracts, journal articles, oral or poster presentation(s), press-release.

21 Clinical Trial Committee Membership:
Will there be an opportunity for CUOG representative(s) to join any pre-existing or proposed committees or serve in the following capacity?:

  • Steering Committee
  • DSMB
  • Clinical Trial Consultant – Liaison
  • Canadian Principal Investigator

CUOG requests that the Sponsor submit a written Response to the Assessment Report. CUOG then distributes a copy of both CUOG Assessment Report and Sponsor’s Response to all members of the Consortium informing them of the content and status of the given project or trial.

A positive outcome of the Assessment Report and Company Response will likely result in a Call for Sites (clinical trial participation) which is centrally dispatched by CUOG Headquarters.