<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT04400656</url>
  </required_header>
  <id_info>
    <org_study_id>19CX5601</org_study_id>
    <nct_id>NCT04400656</nct_id>
  </id_info>
  <brief_title>PROState Pathway Embedded Comparative Trial</brief_title>
  <acronym>IP3-PROSPECT</acronym>
  <official_title>PROState Pathway Embedded Comparative Trial</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Imperial College London</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Imperial Clinical Trials Unit (ICTU)</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Wellcome Trust</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Imperial College London</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The proposal will explore a trial design called the cohort-multiple RCT (cmRCT) or as it has&#xD;
      been recently coined, the Trials WithIn Cohorts (TWICS) design. This design has been used in&#xD;
      a number of disease areas, both benign and cancer. Prostate conditions have been chosen since&#xD;
      they are extremely common and if malignancy occurs the majority of men with the disease are&#xD;
      regarded as living with a chronic condition due to its long natural history and in which&#xD;
      innovative approaches, interventions, treatments or changes in management might have a&#xD;
      significant patient benefit and impact on the NHS. It therefore fits the cmRCT design very&#xD;
      well. Nonetheless, the lessons learned in this study will be of relevance to other disease&#xD;
      spaces.&#xD;
&#xD;
      The TWICS or cmRCT design is currently being used in elderly patients, risk of falls,&#xD;
      depression, hip fracture, Yorkshire Health Study, scleroderma, breast cancer, colorectal&#xD;
      cancer, bladder cancer and kidney cancer, to name a few. In total, a recent systematic review&#xD;
      showed that there were 18 ongoing cmRCT studies with 6 in the UK.&#xD;
&#xD;
      The acceptability and feasibility of the cmRCT in the prostate pathway will be tested. This&#xD;
      is the first time this method will be tested and therefore piloted. In the first part of the&#xD;
      study, the following will be evaluated. What is the accrual rate? What do patients and their&#xD;
      healthcare professionals think of the cmRCT design? Is the data collected robust? What are&#xD;
      the resource requirements of such a study?A number of novel interventions or changes in the&#xD;
      pathway will then be tested and compared to standard care in the cohort that was recruited.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      TRIAL AIMS&#xD;
&#xD;
      The pilot phase of PROSPECT is interested in investigating the a) acceptability and&#xD;
      feasibility of establishing the cohort of men, i.e. putting the questions of Point of Consent&#xD;
      One to men being referred for investigation of prostate cancer, and b) observing the cohort&#xD;
      over the study period and collecting data on the participants pertaining to their disease,&#xD;
      their treatment and their health status.&#xD;
&#xD;
      A) Acceptability&#xD;
&#xD;
      AIM 1.1: To determine what proportion of men with a clinical suspicion for prostate cancer&#xD;
      will participate in an cmRCT.&#xD;
&#xD;
      OBJECTIVE 1.1a: To evaluate proportion of patients approached who agree to participate in the&#xD;
      longitudinal cohort. This will be done by calculating the participation rates from men&#xD;
      approached for invitation to PROSPECT.&#xD;
&#xD;
      AIM 1.2: To explore barriers and facilitators to implementation of a cmRCT in order to&#xD;
      improve and inform patient and/or physician trial information, study processes,&#xD;
      interventions, and recruitment and retention of patients. This will be carried out by&#xD;
      qualitative assessments in the following areas.&#xD;
&#xD;
      OBJECTIVE 1.2a: To investigate by interview the patient experiences and perspectives on;&#xD;
&#xD;
        -  Trial participation,&#xD;
&#xD;
        -  The point at which men are approached by the research team to enter the cohort,&#xD;
&#xD;
        -  Barriers and facilitators to consent to participate in the cohort,&#xD;
&#xD;
        -  Barriers and facilitators to consent to future random selection to undergo a new&#xD;
           healthcare intervention,&#xD;
&#xD;
        -  Acceptability of monitoring of health status and the tools used to do this in the&#xD;
           cohort.&#xD;
&#xD;
      OBJECTIVE 1.2b: To investigate by interview the experiences and perspectives of healthcare&#xD;
      professionals (doctors, nurses and admin staff) on;&#xD;
&#xD;
        -  Trial design and information to patients and healthcare professionals,&#xD;
&#xD;
        -  Feasibility of future random invitation of participants to interventions,&#xD;
&#xD;
        -  Tools used for measuring health status.&#xD;
&#xD;
      B) FEASIBILITY&#xD;
&#xD;
      AIM 2.1: To determine the feasibility of recruitment and logistical implementation of&#xD;
      PROSPECT in different data collecting centres based in different institutions. This will be&#xD;
      broken down into the following sub-questions;&#xD;
&#xD;
      OBJECTIVE 2.1a: Evaluating how the patients are successfully identified and the option of how&#xD;
      inclusion in the trial is presented to them.&#xD;
&#xD;
      OBJECTIVE 2.1b: Evaluate patient questionnaire response rates for pre-treatment quality of&#xD;
      life.&#xD;
&#xD;
      OBJECTIVE 2.1c: Evaluate patient questionnaire response rates at pre-determined intervals&#xD;
      following on from the point of recruitment into the trial to determine how to promote optimal&#xD;
      patient response rate and improve data collection.&#xD;
&#xD;
      OBJECTIVE 2.1d: To evaluate completeness and fidelity of clinical data on the men who&#xD;
      participate in the cohort.&#xD;
&#xD;
      STUDY DESIGN&#xD;
&#xD;
      Design&#xD;
&#xD;
      The key features of a cmRCT are;&#xD;
&#xD;
        1. Explicitly consented recruitment of a large cohort of patients with the condition of&#xD;
           interest.&#xD;
&#xD;
        2. Regular measurement of relevant outcome measures for the whole cohort prospectively in&#xD;
           the long-term.&#xD;
&#xD;
        3. Facility to re-approach cohort participants, who are randomly selected from eligible&#xD;
           patients within the cohort, inviting them to undergo intervention of interest to&#xD;
           researchers with eligible patients not randomly selected entering the control standard&#xD;
           care group (see study flowchart 3.3 / 3.4).&#xD;
&#xD;
        4. &quot;Patient-centred&quot; informed consent. The consent process aims to replicate that used in&#xD;
           the routine health care setting. Once the patient has been randomly selected for a&#xD;
           randomised novel intervention from the eligible patients within the cohort, the second&#xD;
           consent process should include detailed and specific information pertaining to the&#xD;
           particular intervention or change in management they are being invited to undergo for&#xD;
           comparison. Such information will be written and advised using patient representatives&#xD;
           and undergo review following submission to REC.&#xD;
&#xD;
        5. Comparison of the outcomes in the randomly selected patients with the outcomes in&#xD;
           eligible patients not randomly selected.&#xD;
&#xD;
        6. Capacity for multiple randomised controlled trials over time within the cohort&#xD;
           simultaneously.&#xD;
&#xD;
      CONSENT&#xD;
&#xD;
      For men who are participating in the cmRCT there are two points of consent:&#xD;
&#xD;
      POINT OF CONSENT ONE&#xD;
&#xD;
      At Point of Consent One men who are referred for investigation of prostate cancer will be&#xD;
      asked two questions. The first question relates to whether they are willing to join the&#xD;
      cohort and have data collected directly from them over time on a regular basis. This data&#xD;
      will include health-related quality-of-life data (at recruitment, 0-6, 6, 12, 18 &amp; 24 months&#xD;
      post recruitment), linkage to their medical records so that researchers can know what happens&#xD;
      to them over time, and access to other data about them held on national health registry&#xD;
      databases. Also, at point of consent one, prospective participants will be asked (second&#xD;
      question) whether they agree to being randomly selected in the future to interventions or&#xD;
      changes in management in order to compare to standard care. It will be explained that this&#xD;
      second invitation will be on a random basis. In other words, everyone eligible within the&#xD;
      cohort will have the same chance of being randomly selected. The patient would still have the&#xD;
      option of saying 'no' after the random selection when they are approached.&#xD;
&#xD;
      POINT OF CONSENT TWO&#xD;
&#xD;
      The second point of consent is the invitation to undergo an intervention or change in&#xD;
      management that the research team wishes to compare to standard care. Participants will have&#xD;
      already agreed to the possibility of being invited to undergo intervention at Point of&#xD;
      Consent One (i.e. enrolment into the cmRCT). The participant will have been randomly selected&#xD;
      from amongst all the eligible men for the given intervention from within the large cmRCT&#xD;
      cohort prior to being approached by the trial team. Then, the trial team will approach the&#xD;
      participant and invite him to undergo the intervention. This will entail a comprehensive&#xD;
      consent process that pertains directly to the intervention being proposed in a&#xD;
      patient-centred manner. The participant can agree or refuse to undergo the intervention. If&#xD;
      he does not wish to undergo the treatment he will continue under follow-up in PROSPECT.&#xD;
&#xD;
      Participants undergoing intervention will continue to have follow-up in the same manner as&#xD;
      men who have not been randomised from within the cohort and thus provide outcome data to form&#xD;
      the control arm. Comparison of the outcomes of those men who underwent trial intervention&#xD;
      against those who did not will allow us to analyse the effectiveness of the intervention in&#xD;
      as robust a manner as possible given that the key feature of randomisation when creating the&#xD;
      control vs. the intervention arms has been preserved. As such, the control arm of the cmRCT&#xD;
      will be similar to the intervention arm in all features, known and unknown, except the&#xD;
      intervention of interest. This will allow for the maintenance of epistemological superiority&#xD;
      of the data produced for evaluating new tests or treatments whilst getting to this point in a&#xD;
      way that might be more acceptable to patients and therefore more likely to be successful and&#xD;
      efficient for researchers.&#xD;
&#xD;
      The second stage of PROSPECT will be to investigate and evaluate in a similarly careful&#xD;
      manner the feasibility and acceptability of randomising men from the cohort of eligible men&#xD;
      to interventions or changes in management that require evaluation, following submission to&#xD;
      REC. As part of the cmRCT design, these men randomly selected are re-approached and invited&#xD;
      to consider undergoing the intervention of interest. Patients who are randomly allocated to&#xD;
      the control arm will also receive standard of care, and are not informed about their&#xD;
      participation in the control arm. This additional consent will be obtained at the time of&#xD;
      consent for the cohort study.&#xD;
&#xD;
      STUDY SETTING AND POPULATION&#xD;
&#xD;
      All men referred for investigation of prostate cancer. The inclusion criteria for this cohort&#xD;
      is deliberately broad.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">September 8, 2020</start_date>
  <completion_date type="Actual">August 31, 2022</completion_date>
  <primary_completion_date type="Actual">August 31, 2022</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Other</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>1.1a Acceptability - Rate of consent to inclusion</measure>
    <time_frame>6 months</time_frame>
    <description>Rate of consent to inclusion to PROSPECT cohort at the original point of contact by the research team. This will be calculated on an ongoing basis and will be reviewed at 6 months and one year from opening and at the end of the study period</description>
  </primary_outcome>
  <primary_outcome>
    <measure>1.1a Acceptability - Rate of consent to inclusion</measure>
    <time_frame>1 year</time_frame>
    <description>Rate of consent to inclusion to PROSPECT cohort at the original point of contact by the research team. This will be calculated on an ongoing basis and will be reviewed at 6 months and one year from opening and at the end of the study period</description>
  </primary_outcome>
  <primary_outcome>
    <measure>1.1b Acceptability - Experiences and perspectives of patients</measure>
    <time_frame>22 months</time_frame>
    <description>To investigate by interview the experiences and perspectives of patients who:&#xD;
Consented to inclusion in the cohort study,&#xD;
Declined to enter into the cohort,&#xD;
Consented to inclusion in the cohort initially but who subsequently requested to leave the cohort,&#xD;
Structured thematic interviews will be conducted by the researchers who will follow the Interview Questionnaire Template. The interviews will be recorded and transcribed in house before analysis and theme-based extraction of the reasons behind men's decision regarding inclusion in the cohort. Recruitment for qualitative interviews will continue until no further themes emerge.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>1.1e Acceptability - Opinions of healthcare professionals</measure>
    <time_frame>6 months</time_frame>
    <description>The opinions of healthcare professionals who regularly look after men with prostate problems will be sought through semi-structured interviews that focus on implementation, practicality and efficiency of PROSPECT. There will be a different Interview Questionnaire Template for interviews with healthcare professionals.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>1.1e Acceptability - Opinions of healthcare professionals</measure>
    <time_frame>12 months</time_frame>
    <description>The opinions of healthcare professionals who regularly look after men with prostate problems will be sought through semi-structured interviews that focus on implementation, practicality and efficiency of PROSPECT. There will be a different Interview Questionnaire Template for interviews with healthcare professionals.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>2.1a Feasibility - Participants approached vs referral</measure>
    <time_frame>22 months</time_frame>
    <description>Evaluation of the number of men approached to enter PROSPECT against the number of men referred to the participating centres for investigation of prostate cancer.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>2.1b Feasibility - Review of the pathway by which PROSPECT approach men to invite them to the cohort.</measure>
    <time_frame>22 months</time_frame>
    <description>PROSPECT will conduct a review of the pathway by which they approach men to invite them to the cohort. Part of this will be included in the qualitative interviews with men and healthcare professionals. Particular points of interest will be the timing of consent process, the trial personnel who gain consent, and the number of men who give consent who are subsequently not diagnosed with prostate cancer.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>2.1c Feasibility - Quality of Life</measure>
    <time_frame>6 months</time_frame>
    <description>Participants will be given a standard Quality of Life Questionnaire (EQ5D-5L) at the point at which they consent to inclusion into PROSPECT. Data completeness will be calculated at 6 months after opening and on an ongoing basis as long as the study is open.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>2.1c Feasibility - Quality of Life</measure>
    <time_frame>12 months</time_frame>
    <description>Participants will be given a standard Quality of Life Questionnaire (EQ5D-5L) at the point at which they consent to inclusion into PROSPECT. Data completeness will be calculated at 12 months after opening and on an ongoing basis as long as the study is open.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>2.1d Feasibility Outcome - Disease specific Quality of Life</measure>
    <time_frame>Recruitment to cohort</time_frame>
    <description>All participants will be asked to complete questionnaires on disease specific quality of life at the following points;&#xD;
Recruitment to cohort.&#xD;
0-6, 6, 12, 18, 24 months from recruitment to cohort&#xD;
Yearly questionnaires thereafter during inclusion in the cohort if trial remains open (i.e., post pilot phase).&#xD;
PROSPECT will use three self-reporting quality of life validated questionnaires. The responses from the questionnaires will be of value as they will provide an informative vignette of the experience of men after the diagnosis of prostate cancer and they can be compared against the experience of men who are investigated for but not diagnosed with prostate cancer. In terms of evaluating the feasibility of the cmRCT design, PROSPECT will calculate the rates of response from participants with these questionnaires. Questionnaire response rates will also inform PROSPECT of the understanding of the acceptability of the cmRCT design study to patients.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>2.1d Feasibility Outcome - Disease specific Quality of Life</measure>
    <time_frame>0-6 months from recruitment to cohort</time_frame>
    <description>All participants will be asked to complete questionnaires on disease specific quality of life at the following points;&#xD;
Recruitment to cohort.&#xD;
0-6, 6, 12, 18, 24 months from recruitment to cohort&#xD;
Yearly questionnaires thereafter during inclusion in the cohort if trial remains open (i.e., post pilot phase).&#xD;
PROSPECT will use three self-reporting quality of life validated questionnaires. The responses from the questionnaires will be of value as they will provide an informative vignette of the experience of men after the diagnosis of prostate cancer and they can be compared against the experience of men who are investigated for but not diagnosed with prostate cancer. In terms of evaluating the feasibility of the cmRCT design, PROSPECT will calculate the rates of response from participants with these questionnaires. Questionnaire response rates will also inform PROSPECT of the understanding of the acceptability of the cmRCT design study to patients.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>2.1d Feasibility Outcome - Disease specific Quality of Life</measure>
    <time_frame>6 months from recruitment to cohort</time_frame>
    <description>All participants will be asked to complete questionnaires on disease specific quality of life at the following points;&#xD;
Recruitment to cohort.&#xD;
0-6, 6, 12, 18, 24 months from recruitment to cohort&#xD;
Yearly questionnaires thereafter during inclusion in the cohort if trial remains open (i.e., post pilot phase).&#xD;
PROSPECT will use three self-reporting quality of life validated questionnaires. The responses from the questionnaires will be of value as they will provide an informative vignette of the experience of men after the diagnosis of prostate cancer and they can be compared against the experience of men who are investigated for but not diagnosed with prostate cancer. In terms of evaluating the feasibility of the cmRCT design, PROSPECT will calculate the rates of response from participants with these questionnaires. Questionnaire response rates will also inform PROSPECT of the understanding of the acceptability of the cmRCT design study to patients.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>2.1d Feasibility Outcome - Disease specific Quality of Life</measure>
    <time_frame>12 months from recruitment to cohort</time_frame>
    <description>All participants will be asked to complete questionnaires on disease specific quality of life at the following points;&#xD;
Recruitment to cohort.&#xD;
0-6, 6, 12, 18, 24 months from recruitment to cohort&#xD;
Yearly questionnaires thereafter during inclusion in the cohort if trial remains open (i.e., post pilot phase).&#xD;
PROSPECT will use three self-reporting quality of life validated questionnaires. The responses from the questionnaires will be of value as they will provide an informative vignette of the experience of men after the diagnosis of prostate cancer and they can be compared against the experience of men who are investigated for but not diagnosed with prostate cancer. In terms of evaluating the feasibility of the cmRCT design, PROSPECT will calculate the rates of response from participants with these questionnaires. Questionnaire response rates will also inform PROSPECT of the understanding of the acceptability of the cmRCT design study to patients.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>2.1d Feasibility Outcome - Disease specific Quality of Life</measure>
    <time_frame>18 months from recruitment to cohort</time_frame>
    <description>All participants will be asked to complete questionnaires on disease specific quality of life at the following points;&#xD;
Recruitment to cohort.&#xD;
0-6, 6, 12, 18, 24 months from recruitment to cohort&#xD;
Yearly questionnaires thereafter during inclusion in the cohort if trial remains open (i.e., post pilot phase).&#xD;
PROSPECT will use three self-reporting quality of life validated questionnaires. The responses from the questionnaires will be of value as they will provide an informative vignette of the experience of men after the diagnosis of prostate cancer and they can be compared against the experience of men who are investigated for but not diagnosed with prostate cancer. In terms of evaluating the feasibility of the cmRCT design, PROSPECT will calculate the rates of response from participants with these questionnaires. Questionnaire response rates will also inform PROSPECT of the understanding of the acceptability of the cmRCT design study to patients.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>2.1d Feasibility Outcome - Disease specific Quality of Life</measure>
    <time_frame>24 months from recruitment to cohort</time_frame>
    <description>All participants will be asked to complete questionnaires on disease specific quality of life at the following points;&#xD;
Recruitment to cohort.&#xD;
0-6, 6, 12, 18, 24 months from recruitment to cohort&#xD;
Yearly questionnaires thereafter during inclusion in the cohort if trial remains open (i.e., post pilot phase).&#xD;
PROSPECT will use three self-reporting quality of life validated questionnaires. The responses from the questionnaires will be of value as they will provide an informative vignette of the experience of men after the diagnosis of prostate cancer and they can be compared against the experience of men who are investigated for but not diagnosed with prostate cancer. In terms of evaluating the feasibility of the cmRCT design, PROSPECT will calculate the rates of response from participants with these questionnaires. Questionnaire response rates will also inform PROSPECT of the understanding of the acceptability of the cmRCT design study to patients.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>2.1e Feasibility - Data collection</measure>
    <time_frame>24 months after opening PROSPECT and yearly thereafter in order to monitor any trends</time_frame>
    <description>Feasibility of collecting data from the participating centres evidenced by the completeness of data for cohort participants including; i. Subject Data: age, co-morbidities, ECOG/WHO Performance Status, ethnic risk, family risk ii. Disease Characteristics: PSA, MRI (volume, score), biopsy findings (cancer or not, grade if cancer, length of maximum cancer, other pathology), TNM stage if cancer iii. Treatment Data: modality, follow-up, adjuvant and salvage treatments, mortality Analysis will be conducted at one year after opening the PROSPECT and yearly thereafter in order to monitor any trends in improving or faltering data accrual on participants, as long as the study is open.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Qualitative Outcome Measure 1- Trial Participants</measure>
    <time_frame>22 months</time_frame>
    <description>The integrated qualitative component will explore patients who;&#xD;
Consented to inclusion in the cohort study,&#xD;
Declined to enter into the cohort,&#xD;
Consented to inclusion in the cohort initially but who subsequently requested to leave the cohort&#xD;
Structured thematic interviews will be conducted by the researchers who will follow the Interview Questionnaire Template. The interviews will be recorded and transcribed in house before analysis and theme-based extraction of the reasons behind men's</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Qualitative Outcome Measure 2 - Healthcare participants</measure>
    <time_frame>6 months</time_frame>
    <description>The opinions of healthcare professionals who regularly look after men with prostate cancer will be sought through conducting semi-structured interviews that focus on ethics, implementation, practicality and efficiency of PROSPECT. There will be a different Interview Questionnaire Template for interviews with healthcare professionals.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Qualitative Outcome Measure 2 - Healthcare participants</measure>
    <time_frame>12 months</time_frame>
    <description>The opinions of healthcare professionals who regularly look after men with prostate cancer will be sought through conducting semi-structured interviews that focus on ethics, implementation, practicality and efficiency of PROSPECT. There will be a different Interview Questionnaire Template for interviews with healthcare professionals.</description>
  </secondary_outcome>
  <enrollment type="Actual">139</enrollment>
  <condition>Prostate Cancer</condition>
  <condition>Non-metastatic Prostate Cancer</condition>
  <condition>Metastatic Prostate Cancer</condition>
  <condition>Prostate Adenocarcinoma</condition>
  <condition>Metastatic Prostate Carcinoma in the Soft Tissue</condition>
  <condition>Prostate Cancer Metastatic</condition>
  <eligibility>
    <study_pop>
      <textblock>
        All men referred for investigation of prostate cancer&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Men aged 18 years old and over who are referred for investigations for urinary&#xD;
             symptoms or elevated serum prostate specific antigen (PSA) levels or other risk&#xD;
             factors for possible prostate malignancy.&#xD;
&#xD;
          2. An understanding of the English language sufficient to understand written and verbal&#xD;
             information about the trial and consent process.&#xD;
&#xD;
          3. Estimated life expectancy of 5 years or more.&#xD;
&#xD;
          4. Signed informed consent.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        1. Men who are unable to give informed consent.&#xD;
      </textblock>
    </criteria>
    <gender>Male</gender>
    <gender_based>Yes</gender_based>
    <gender_description>Men with possible prostate malignancy</gender_description>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Hashim Ahmed</last_name>
    <role>Principal Investigator</role>
    <affiliation>Imperial College London</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>West Middlesex University Hospital</name>
      <address>
        <city>Isleworth</city>
        <state>Middlesex</state>
        <zip>TW7 6AF</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ashford &amp; St Peter's Hospitals (ASPH) NHS Foundation Trust</name>
      <address>
        <city>Chertsey</city>
        <state>Surrey</state>
        <zip>KT16 0PZ</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Imperial College Healthcare NHS Trust</name>
      <address>
        <city>London</city>
        <zip>W6 8RF</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United Kingdom</country>
  </location_countries>
  <verification_date>September 2022</verification_date>
  <study_first_submitted>May 11, 2020</study_first_submitted>
  <study_first_submitted_qc>May 19, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">May 22, 2020</study_first_posted>
  <last_update_submitted>September 22, 2022</last_update_submitted>
  <last_update_submitted_qc>September 22, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">September 23, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>prostate cancer</keyword>
  <keyword>Non-metastatic Prostate Cancer</keyword>
  <keyword>Metastatic Prostate Cancer</keyword>
  <keyword>Prostate Adenocarcinoma</keyword>
  <keyword>Metastatic Prostate Carcinoma in the Soft Tissue</keyword>
  <keyword>Prostate Cancer Metastatic</keyword>
  <keyword>Clinical Trial Design</keyword>
  <keyword>cohort multiple randomised controlled trial</keyword>
  <keyword>cmRCT</keyword>
  <keyword>Trials Within Cohorts</keyword>
  <keyword>TWICS</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Prostatic Neoplasms</mesh_term>
    <mesh_term>Adenocarcinoma</mesh_term>
  </condition_browse>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT04400656
org study id: 19CX5601
nct id: NCT04400656
lead sponsor: 
collaborator: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
The proposal will explore a trial design called the cohort-multiple RCT (cmRCT) or as it has
      been recently coined, the Trials WithIn Cohorts (TWICS) design. This design has been used in
      a number of disease areas, both benign and cancer. Prostate conditions have been chosen since
      they are extremely common and if malignancy occurs the majority of men with the disease are
      regarded as living with a chronic condition due to its long natural history and in which
      innovative approaches, interventions, treatments or changes in management might have a
      significant patient benefit and impact on the NHS. It therefore fits the cmRCT design very
      well. Nonetheless, the lessons learned in this study will be of relevance to other disease
      spaces.

      The TWICS or cmRCT design is currently being used in elderly patients, risk of falls,
      depression, hip fracture, Yorkshire Health Study, scleroderma, breast cancer, colorectal
      cancer, bladder cancer and kidney cancer, to name a few. In total, a recent systematic review
      showed that there were 18 ongoing cmRCT studies with 6 in the UK.

      The acceptability and feasibility of the cmRCT in the prostate pathway will be tested. This
      is the first time this method will be tested and therefore piloted. In the first part of the
      study, the following will be evaluated. What is the accrual rate? What do patients and their
      healthcare professionals think of the cmRCT design? Is the data collected robust? What are
      the resource requirements of such a study?A number of novel interventions or changes in the
      pathway will then be tested and compared to standard care in the cohort that was recruited.
TRIAL AIMS

      The pilot phase of PROSPECT is interested in investigating the a) acceptability and
      feasibility of establishing the cohort of men, i.e. putting the questions of Point of Consent
      One to men being referred for investigation of prostate cancer, and b) observing the cohort
      over the study period and collecting data on the participants pertaining to their disease,
      their treatment and their health status.

      A) Acceptability

      AIM 1.1: To determine what proportion of men with a clinical suspicion for prostate cancer
      will participate in an cmRCT.

      OBJECTIVE 1.1a: To evaluate proportion of patients approached who agree to participate in the
      longitudinal cohort. This will be done by calculating the participation rates from men
      approached for invitation to PROSPECT.

      AIM 1.2: To explore barriers and facilitators to implementation of a cmRCT in order to
      improve and inform patient and/or physician trial information, study processes,
      interventions, and recruitment and retention of patients. This will be carried out by
      qualitative assessments in the following areas.

      OBJECTIVE 1.2a: To investigate by interview the patient experiences and perspectives on;

        -  Trial participation,

        -  The point at which men are approached by the research team to enter the cohort,

        -  Barriers and facilitators to consent to participate in the cohort,

        -  Barriers and facilitators to consent to future random selection to undergo a new
           healthcare intervention,

        -  Acceptability of monitoring of health status and the tools used to do this in the
           cohort.

      OBJECTIVE 1.2b: To investigate by interview the experiences and perspectives of healthcare
      professionals (doctors, nurses and admin staff) on;

        -  Trial design and information to patients and healthcare professionals,

        -  Feasibility of future random invitation of participants to interventions,

        -  Tools used for measuring health status.

      B) FEASIBILITY

      AIM 2.1: To determine the feasibility of recruitment and logistical implementation of
      PROSPECT in different data collecting centres based in different institutions. This will be
      broken down into the following sub-questions;

      OBJECTIVE 2.1a: Evaluating how the patients are successfully identified and the option of how
      inclusion in the trial is presented to them.

      OBJECTIVE 2.1b: Evaluate patient questionnaire response rates for pre-treatment quality of
      life.

      OBJECTIVE 2.1c: Evaluate patient questionnaire response rates at pre-determined intervals
      following on from the point of recruitment into the trial to determine how to promote optimal
      patient response rate and improve data collection.

      OBJECTIVE 2.1d: To evaluate completeness and fidelity of clinical data on the men who
      participate in the cohort.

      STUDY DESIGN

      Design

      The key features of a cmRCT are;

        1. Explicitly consented recruitment of a large cohort of patients with the condition of
           interest.

        2. Regular measurement of relevant outcome measures for the whole cohort prospectively in
           the long-term.

        3. Facility to re-approach cohort participants, who are randomly selected from eligible
           patients within the cohort, inviting them to undergo intervention of interest to
           researchers with eligible patients not randomly selected entering the control standard
           care group (see study flowchart 3.3 / 3.4).

        4. "Patient-centred" informed consent. The consent process aims to replicate that used in
           the routine health care setting. Once the patient has been randomly selected for a
           randomised novel intervention from the eligible patients within the cohort, the second
           consent process should include detailed and specific information pertaining to the
           particular intervention or change in management they are being invited to undergo for
           comparison. Such information will be written and advised using patient representatives
           and undergo review following submission to REC.

        5. Comparison of the outcomes in the randomly selected patients with the outcomes in
           eligible patients not randomly selected.

        6. Capacity for multiple randomised controlled trials over time within the cohort
           simultaneously.

      CONSENT

      For men who are participating in the cmRCT there are two points of consent:

      POINT OF CONSENT ONE

      At Point of Consent One men who are referred for investigation of prostate cancer will be
      asked two questions. The first question relates to whether they are willing to join the
      cohort and have data collected directly from them over time on a regular basis. This data
      will include health-related quality-of-life data (at recruitment, 0-6, 6, 12, 18 & 24 months
      post recruitment), linkage to their medical records so that researchers can know what happens
      to them over time, and access to other data about them held on national health registry
      databases. Also, at point of consent one, prospective participants will be asked (second
      question) whether they agree to being randomly selected in the future to interventions or
      changes in management in order to compare to standard care. It will be explained that this
      second invitation will be on a random basis. In other words, everyone eligible within the
      cohort will have the same chance of being randomly selected. The patient would still have the
      option of saying 'no' after the random selection when they are approached.

      POINT OF CONSENT TWO

      The second point of consent is the invitation to undergo an intervention or change in
      management that the research team wishes to compare to standard care. Participants will have
      already agreed to the possibility of being invited to undergo intervention at Point of
      Consent One (i.e. enrolment into the cmRCT). The participant will have been randomly selected
      from amongst all the eligible men for the given intervention from within the large cmRCT
      cohort prior to being approached by the trial team. Then, the trial team will approach the
      participant and invite him to undergo the intervention. This will entail a comprehensive
      consent process that pertains directly to the intervention being proposed in a
      patient-centred manner. The participant can agree or refuse to undergo the intervention. If
      he does not wish to undergo the treatment he will continue under follow-up in PROSPECT.

      Participants undergoing intervention will continue to have follow-up in the same manner as
      men who have not been randomised from within the cohort and thus provide outcome data to form
      the control arm. Comparison of the outcomes of those men who underwent trial intervention
      against those who did not will allow us to analyse the effectiveness of the intervention in
      as robust a manner as possible given that the key feature of randomisation when creating the
      control vs. the intervention arms has been preserved. As such, the control arm of the cmRCT
      will be similar to the intervention arm in all features, known and unknown, except the
      intervention of interest. This will allow for the maintenance of epistemological superiority
      of the data produced for evaluating new tests or treatments whilst getting to this point in a
      way that might be more acceptable to patients and therefore more likely to be successful and
      efficient for researchers.

      The second stage of PROSPECT will be to investigate and evaluate in a similarly careful
      manner the feasibility and acceptability of randomising men from the cohort of eligible men
      to interventions or changes in management that require evaluation, following submission to
      REC. As part of the cmRCT design, these men randomly selected are re-approached and invited
      to consider undergoing the intervention of interest. Patients who are randomly allocated to
      the control arm will also receive standard of care, and are not informed about their
      participation in the control arm. This additional consent will be obtained at the time of
      consent for the cohort study.

      STUDY SETTING AND POPULATION

      All men referred for investigation of prostate cancer. The inclusion criteria for this cohort
      is deliberately broad.
observational model: Other
time perspective: Prospective
measure: 1.1a Acceptability - Rate of consent to inclusion
time frame: 6 months
description: Rate of consent to inclusion to PROSPECT cohort at the original point of contact by the research team. This will be calculated on an ongoing basis and will be reviewed at 6 months and one year from opening and at the end of the study period
measure: 1.1a Acceptability - Rate of consent to inclusion
time frame: 1 year
description: Rate of consent to inclusion to PROSPECT cohort at the original point of contact by the research team. This will be calculated on an ongoing basis and will be reviewed at 6 months and one year from opening and at the end of the study period
measure: 1.1b Acceptability - Experiences and perspectives of patients
time frame: 22 months
description: To investigate by interview the experiences and perspectives of patients who:
Consented to inclusion in the cohort study,
Declined to enter into the cohort,
Consented to inclusion in the cohort initially but who subsequently requested to leave the cohort,
Structured thematic interviews will be conducted by the researchers who will follow the Interview Questionnaire Template. The interviews will be recorded and transcribed in house before analysis and theme-based extraction of the reasons behind men's decision regarding inclusion in the cohort. Recruitment for qualitative interviews will continue until no further themes emerge.
measure: 1.1e Acceptability - Opinions of healthcare professionals
time frame: 6 months
description: The opinions of healthcare professionals who regularly look after men with prostate problems will be sought through semi-structured interviews that focus on implementation, practicality and efficiency of PROSPECT. There will be a different Interview Questionnaire Template for interviews with healthcare professionals.
measure: 1.1e Acceptability - Opinions of healthcare professionals
time frame: 12 months
description: The opinions of healthcare professionals who regularly look after men with prostate problems will be sought through semi-structured interviews that focus on implementation, practicality and efficiency of PROSPECT. There will be a different Interview Questionnaire Template for interviews with healthcare professionals.
measure: 2.1a Feasibility - Participants approached vs referral
time frame: 22 months
description: Evaluation of the number of men approached to enter PROSPECT against the number of men referred to the participating centres for investigation of prostate cancer.
measure: 2.1b Feasibility - Review of the pathway by which PROSPECT approach men to invite them to the cohort.
time frame: 22 months
description: PROSPECT will conduct a review of the pathway by which they approach men to invite them to the cohort. Part of this will be included in the qualitative interviews with men and healthcare professionals. Particular points of interest will be the timing of consent process, the trial personnel who gain consent, and the number of men who give consent who are subsequently not diagnosed with prostate cancer.
measure: 2.1c Feasibility - Quality of Life
time frame: 6 months
description: Participants will be given a standard Quality of Life Questionnaire (EQ5D-5L) at the point at which they consent to inclusion into PROSPECT. Data completeness will be calculated at 6 months after opening and on an ongoing basis as long as the study is open.
measure: 2.1c Feasibility - Quality of Life
time frame: 12 months
description: Participants will be given a standard Quality of Life Questionnaire (EQ5D-5L) at the point at which they consent to inclusion into PROSPECT. Data completeness will be calculated at 12 months after opening and on an ongoing basis as long as the study is open.
measure: 2.1d Feasibility Outcome - Disease specific Quality of Life
time frame: Recruitment to cohort
description: All participants will be asked to complete questionnaires on disease specific quality of life at the following points;
Recruitment to cohort.
0-6, 6, 12, 18, 24 months from recruitment to cohort
Yearly questionnaires thereafter during inclusion in the cohort if trial remains open (i.e., post pilot phase).
PROSPECT will use three self-reporting quality of life validated questionnaires. The responses from the questionnaires will be of value as they will provide an informative vignette of the experience of men after the diagnosis of prostate cancer and they can be compared against the experience of men who are investigated for but not diagnosed with prostate cancer. In terms of evaluating the feasibility of the cmRCT design, PROSPECT will calculate the rates of response from participants with these questionnaires. Questionnaire response rates will also inform PROSPECT of the understanding of the acceptability of the cmRCT design study to patients.
measure: 2.1d Feasibility Outcome - Disease specific Quality of Life
time frame: 0-6 months from recruitment to cohort
description: All participants will be asked to complete questionnaires on disease specific quality of life at the following points;
Recruitment to cohort.
0-6, 6, 12, 18, 24 months from recruitment to cohort
Yearly questionnaires thereafter during inclusion in the cohort if trial remains open (i.e., post pilot phase).
PROSPECT will use three self-reporting quality of life validated questionnaires. The responses from the questionnaires will be of value as they will provide an informative vignette of the experience of men after the diagnosis of prostate cancer and they can be compared against the experience of men who are investigated for but not diagnosed with prostate cancer. In terms of evaluating the feasibility of the cmRCT design, PROSPECT will calculate the rates of response from participants with these questionnaires. Questionnaire response rates will also inform PROSPECT of the understanding of the acceptability of the cmRCT design study to patients.
measure: 2.1d Feasibility Outcome - Disease specific Quality of Life
time frame: 6 months from recruitment to cohort
description: All participants will be asked to complete questionnaires on disease specific quality of life at the following points;
Recruitment to cohort.
0-6, 6, 12, 18, 24 months from recruitment to cohort
Yearly questionnaires thereafter during inclusion in the cohort if trial remains open (i.e., post pilot phase).
PROSPECT will use three self-reporting quality of life validated questionnaires. The responses from the questionnaires will be of value as they will provide an informative vignette of the experience of men after the diagnosis of prostate cancer and they can be compared against the experience of men who are investigated for but not diagnosed with prostate cancer. In terms of evaluating the feasibility of the cmRCT design, PROSPECT will calculate the rates of response from participants with these questionnaires. Questionnaire response rates will also inform PROSPECT of the understanding of the acceptability of the cmRCT design study to patients.
measure: 2.1d Feasibility Outcome - Disease specific Quality of Life
time frame: 12 months from recruitment to cohort
description: All participants will be asked to complete questionnaires on disease specific quality of life at the following points;
Recruitment to cohort.
0-6, 6, 12, 18, 24 months from recruitment to cohort
Yearly questionnaires thereafter during inclusion in the cohort if trial remains open (i.e., post pilot phase).
PROSPECT will use three self-reporting quality of life validated questionnaires. The responses from the questionnaires will be of value as they will provide an informative vignette of the experience of men after the diagnosis of prostate cancer and they can be compared against the experience of men who are investigated for but not diagnosed with prostate cancer. In terms of evaluating the feasibility of the cmRCT design, PROSPECT will calculate the rates of response from participants with these questionnaires. Questionnaire response rates will also inform PROSPECT of the understanding of the acceptability of the cmRCT design study to patients.
measure: 2.1d Feasibility Outcome - Disease specific Quality of Life
time frame: 18 months from recruitment to cohort
description: All participants will be asked to complete questionnaires on disease specific quality of life at the following points;
Recruitment to cohort.
0-6, 6, 12, 18, 24 months from recruitment to cohort
Yearly questionnaires thereafter during inclusion in the cohort if trial remains open (i.e., post pilot phase).
PROSPECT will use three self-reporting quality of life validated questionnaires. The responses from the questionnaires will be of value as they will provide an informative vignette of the experience of men after the diagnosis of prostate cancer and they can be compared against the experience of men who are investigated for but not diagnosed with prostate cancer. In terms of evaluating the feasibility of the cmRCT design, PROSPECT will calculate the rates of response from participants with these questionnaires. Questionnaire response rates will also inform PROSPECT of the understanding of the acceptability of the cmRCT design study to patients.
measure: 2.1d Feasibility Outcome - Disease specific Quality of Life
time frame: 24 months from recruitment to cohort
description: All participants will be asked to complete questionnaires on disease specific quality of life at the following points;
Recruitment to cohort.
0-6, 6, 12, 18, 24 months from recruitment to cohort
Yearly questionnaires thereafter during inclusion in the cohort if trial remains open (i.e., post pilot phase).
PROSPECT will use three self-reporting quality of life validated questionnaires. The responses from the questionnaires will be of value as they will provide an informative vignette of the experience of men after the diagnosis of prostate cancer and they can be compared against the experience of men who are investigated for but not diagnosed with prostate cancer. In terms of evaluating the feasibility of the cmRCT design, PROSPECT will calculate the rates of response from participants with these questionnaires. Questionnaire response rates will also inform PROSPECT of the understanding of the acceptability of the cmRCT design study to patients.
measure: 2.1e Feasibility - Data collection
time frame: 24 months after opening PROSPECT and yearly thereafter in order to monitor any trends
description: Feasibility of collecting data from the participating centres evidenced by the completeness of data for cohort participants including; i. Subject Data: age, co-morbidities, ECOG/WHO Performance Status, ethnic risk, family risk ii. Disease Characteristics: PSA, MRI (volume, score), biopsy findings (cancer or not, grade if cancer, length of maximum cancer, other pathology), TNM stage if cancer iii. Treatment Data: modality, follow-up, adjuvant and salvage treatments, mortality Analysis will be conducted at one year after opening the PROSPECT and yearly thereafter in order to monitor any trends in improving or faltering data accrual on participants, as long as the study is open.
measure: Qualitative Outcome Measure 1- Trial Participants
time frame: 22 months
description: The integrated qualitative component will explore patients who;
Consented to inclusion in the cohort study,
Declined to enter into the cohort,
Consented to inclusion in the cohort initially but who subsequently requested to leave the cohort
Structured thematic interviews will be conducted by the researchers who will follow the Interview Questionnaire Template. The interviews will be recorded and transcribed in house before analysis and theme-based extraction of the reasons behind men's
measure: Qualitative Outcome Measure 2 - Healthcare participants
time frame: 6 months
description: The opinions of healthcare professionals who regularly look after men with prostate cancer will be sought through conducting semi-structured interviews that focus on ethics, implementation, practicality and efficiency of PROSPECT. There will be a different Interview Questionnaire Template for interviews with healthcare professionals.
measure: Qualitative Outcome Measure 2 - Healthcare participants
time frame: 12 months
description: The opinions of healthcare professionals who regularly look after men with prostate cancer will be sought through conducting semi-structured interviews that focus on ethics, implementation, practicality and efficiency of PROSPECT. There will be a different Interview Questionnaire Template for interviews with healthcare professionals.
study pop: 
sampling method: Probability Sample
criteria: 
gender: Male
gender based: Yes
gender description: Men with possible prostate malignancy
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Hashim Ahmed
role: Principal Investigator
affiliation: Imperial College London
facility: 
facility: 
facility: 
country: United Kingdom
responsible party type: Sponsor
mesh term: Prostatic Neoplasms
mesh term: Adenocarcinoma