Clinical Trial in Nut Shell

Screening and Recruitment of Study Subjects in Clinical Research

Screening and Recruitment of Study Subjects

It is important that the Investigator resolves all questions from his/her staff concerning the interpretation of inclusion/exclusion criteria.

The Investigator should be able to dedicate time to the recruitment of suitable trial subjects – the consultation time for recruitment of each subject is likely to be longer than the time required for normal consultation.

The Investigator must ensure the unbiased selection of an adequate number of suitable study subjects as defined by the Protocol.

The Investigator must allow study subjects who meet the inclusion criteria the opportunity to decide for themselves whether or not to be entered into the study.

The Investigator must document the identification of subjects who entered trial screening by completing a subject screening/enrolment log.

Obtain Informed Consent from All Trial Subjects

The concept of obtaining informed consent is considered to be the heart of GCP.  Informed consent is the process by which a study subject voluntarily confirms his/her willingness to participate in the trial. Only study subjects who have fully understood all aspects of their participation in the trial can make proper judgements and give their consent to participate in the trial.

  Information on disease prevention and transmission must be provided to the study subjects for the whole of the trial period. Before any subject enters a trial, and before any study-related procedures begin, written informed consent must be obtained from the subject and/or his/her legally acceptable representative. In the case of a screening test which requires biological specimens to be collected prior to entering a trial, two types of consent form must be obtained, one for biological specimen collection and analysis, and the other for participation in the study after satisfactory laboratory results respecting the inclusion criteria have been obtained. Study subjects found ineligible at screening (for medical reasons) should receive supportive counselling, any necessary and available treatment and referral for continued counselling.

The Investigator can delegate the consent process to an appropriately qualified person; however, the Investigator should see the subject afterwards to ensure that the consent has been properly

obtained.  Verbal and written information given to the trial subject should be in simple terms and in his/her first language.  Medical terms should be avoided.

The Investigator/designated person should perform informed consent procedures fully with each subject during recruitment:

Ø      The informed consent form should be personally dated and signed by the trial subject and/or his/her legally acceptable representative as well as the Investigator/designated person responsible for the informed consent procedures.

Ø      If the study subject and/or legally acceptable representative is (are) unable to read, an impartial witness for the Investigator should be present during the entire informed consent discussion. After oral approval by the study subject and/or legally acceptable representative, the witness must sign and personally date the informed consent form and attest that the information was accurately explained and apparently understood, and that informed consent was given freely by the subject and/or legally acceptable representative. The subject and/or legally acceptable representative should personally sign and date the form if capable of doing so.

Ø      The study subject and/or legally acceptable representative should be given a copy of the signed and dated informed consent form and any other written information.

Ø      The original signed and dated informed consent form should be kept in the Investigator's File with the study subject’s data.

Trial subjects and/or their legally acceptable representatives should be kept informed throughout the trial of any new findings or information about the tested product which might be of consequence to their participation in the trial. They should receive updates of the signed and dated consent form as well as copies of any amendments to the written information. Updates of the original signed and dated consent form should be kept in the Investigator's File.

Study Subjects Data and Documents For Clinical Research

Study Subjects Data and Documents For Clinical Research

Ø            All signed and dated informed consent forms (for enrolled and screened subjects).

Ø            Study subject screening and/or enrolment log.

Ø            Study subject identification list.

Ø            Copy of all Case Report Forms (CRFs).

Ø            Copy of the Serious Adverse Event form.

Ø            Copy of documentation of CRF corrections.

Ø            All study subjects source documents including laboratory results.

Ø            Copy of all subjects CRFs retrieval certificate.

During the clinical research studies

The trial can be initiated (begin screening and/or enrolment of trial subjects) only after the Clinical Monitor has satisfactorily conducted a Trial Initiation Monitoring Visit and the TDR Clinical Coordinator has given written authorization.

Investigator’s File, Including Storage and Retention

On initiation of the study, the Investigator must prepare a file containing documents related to the trial.  During the study, the Investigator is responsible for updating the File and regularly adding trial-related documents.

The Investigator should keep the File in a locked cabinet, in a secure area accessible only to the Investigator and authorized study staff.  The Investigator File and associated source documents should be retained for the time agreed with TDR/sponsors. Patient identification codes should be kept for at least 15 years after completion of the trial. Written approval from sponsors must be obtained prior to destroying records.

The Investigator's File contains:

Ø      Administrative and Regulatory Documents

Ø      Composition of IEC/IRB.

Ø      Local regulatory requirements.

Ø      IEC/IRB and other authorities’ written approval for all documents (protocol, informed consent(s) and any written information including advertisements for recruitment of study subjects).

Ø      IEC/IRB and other authorities’ written approval for protocol amendments.

Ø      Correspondence with the Ethics Committee and the Authorities, including:

·         Protocol submission.

·         Amendment submission, if any.

·         Protocol modification notification, if any.

·         Interim report/written summaries of the trial, if applicable.

·         Final Report/written summaries of the trial, if applicable.

·         Product importation authorization.

Ø       Correspondence about product importation.

Ø       For studies under IND, a copy of the completed and signed Form FDA 1572.

Ø       Investigator’ s and Co/Sub-investigators’ C.V.s

Ø       New Investigator and Sub-investigators’ C.V.s, if appropriate.

Ø       Authorized Staff Form (ASF).

Ø       Technical Services Agreement (TSA) signed/dated by both parties.

Ø       Signed confidentiality agreement.

Ø       Signed agreement stating that products will not be used before the Trial Initiation

Ø       Monitoring Visit has been made and approval from the TDR Clinical Coordinator obtained.

Ø       Copy of the insurance certificate/other insurance.

Ø       ICH GCP guideline.

Ø       TDR/TDP investigator’ s SOPs.

Ø       Study Archiving Form (copy).

Ø       Copy of the Investigator's interim report/written summaries of the trial to the IEC/IRB and authorities, if applicable.

Ø       Copy of the Investigator's final report/written summaries of the trial to the IEC/IRB and authorities, if applicable.

Correspondence and Monitoring

Ø       Correspondence with TDR/sponsoring agencies (including the telephone call, E-mail etc).

Ø       Notes of meetings with TDR/sponsoring agencies.

Ø       Summary list of site visits (copy).

Ø       Trial Initiation Monitoring Report (copy).

Ø       Notification by Investigator to TDR/Sponsor of serious adverse event and related reports.

Ø       Documentation of serious adverse event reporting by TDR/Sponsor to other investigators.

Ø       Correspondence about important requests.

Ø       Investigator interim report/summaries of the trial for TDR/sponsoring agencies, if applicable.

Ø       Investigator final report/summary of the trial for TDR/sponsoring agencies, if applicable.

Trial Documents

Ø       General documents

Ø       Investigator’ s brochure, with updates, if any

Ø       Approved protocol and amendments, signed and dated by the Investigator(s) and sponsoring agencies, and new protocol amendments, if any.

Ø       Approved informed consent and any other written information including all translations, and advertisements for recruitment of study subjects.

Ø       Informed consent procedure.

Ø       Clinical Trial Final Report (if available during the Study Closeout Visit).

Data reporting

Ø       Blank CRF.

Ø       Blank SAE/UAE forms.

Ø       Blank source document if not existing on site.

Ø       Case Report Form completion procedure.

Ø       Adverse event reporting procedure.

Ø       Blank screening and enrolment log.

Product

Ø       Product certificate/batch release.

Ø       Certificate of extension of the batch expiry date, if applicable.

Ø       Dispatch notes (original) and acknowledgement of receipt (copy) (in case of new delivery).

Ø       Randomization list/envelope or acknowledgement of receipt.

Ø       Randomization list/envelope or randomization list/envelope retrieval certificate.

Ø       Code Breaking list/randomization envelope retrieval certificate.

Ø       Subject assignment list.

Ø       Product management procedure.

Ø       Product exportation/importation authorization

Ø       Product accountability log.

Ø       Product management form.

Ø       Return of unused products form, or product destruction certificate if destroyed on site.

Ø       Temperature recording log, if appropriate (especially for vaccines/biologicals).

Ø       Other products-related trial documents.

Laboratory specimens.

Ø       Laboratory certification/normal ranges/update of normal values.

Ø       Reactive dispatch note and acknowledgement of receipt.

Ø       Specimen management procedures (collection, performing assay, storage, results).

Ø       Subject specimen collection log.

Ø       Shipment note, if appropriate.

Ø       Temperature recording log, if appropriate (deep frozen samples).

Ø       Record of retained laboratory specimens, if any, to document the location and identification of retained specimens if assays need to be repeated.

Ø       Other laboratory specimen related trial documents.

Ø       Specimen management procedures (collection, performing assay, storage, results).

Ø       Subject specimen collection log.

Ø       Shipment note, if appropriate.

Ø       Temperature recording log, if appropriate (deep frozen samples).

Ø       Record of retained laboratory specimens, if any, to document the location and identification of retained specimens if assays need to be repeated.

Ø       Other laboratory specimen related trial documents.

Trial supplies/equipment

Ø       Material/equipment dispatch note (original) and acknowledgement of receipt (copy).

Ø       Return of trial material/equipment certificate (copy).

Ø       Trial document dispatch note (original) and acknowledgement of receipt (copy) (CRFs, all trial logs).

Ø       Return of trial document certificate (copy).

Probe Tuning :NMR

Probe Tuning :NMR

Probe tuning must be matched to the sample in order to minimize pulse widths and maximize sensitivity.  Although the effects are small for routine proton spectra, they can be dramatic for more complex pulse sequences.  Although the tuning changes between different organic solvents usually do not justify the effort to tune, if you are changing from an organic solvent to water or D₂O, retuning the probe is usually worthwhile.  If you are starting a long experiment, you will want to check the probe tuning.

The wobb command allows you to tune and match a probe in an easy way even when the coil is heavily mistuned and mismatched. First copy the parameters for the nucleus you wish to observe.

Now enter the acquisition window by clicking Acquire/Observe fid window and start the wobble routine by clicking on Acquire/Acquisition parameter setup/Tune probehead. Alternatively enter acqu and then wobb via the keyboard. The acquisition is started and after a few seconds the wobble curve is displayed and refreshed continuously. A vertical line is drawn at the center frequency

(SFOx) to provide optical information on the frequency which is to be tuned. The horizontal axis of the coordinate system is scaled in MHz and labeled accordingly. Useful information like nucleus, tuning frequency, frequency of the minimum of the wobble curve and wobble width, is displayed in the information window. Simultaneously the LED display on the preamplifier is set and refreshed accordingly. The wobble curve shows a dip downwards which changes while you turn the tune or match knobs of the probe.  Example displays in Figure. 

1. Turn the tune knob (tune sliders on the indirect probe) so that the dip moves towards the center of the screen. Keep on turning until the dip is exactly in the center across the vertical line.

2. Turn the match knob (match sliders on the indirect probe) so that the dip becomes deeper. Keep on turning until the base of the dip is at a minimum. This occurs at the zero level line for most probes.

3. On most probes the matching influences the tuning and vice versa, so repeat steps 1 and 2 until the dip is exactly in the center of the screen and its base at minimum level. Then the probe is tuned and matched.

When you are finished with tuning and matching stop wobb by activating the stop button or by entering stop via the keyboard.