<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/NCT04407676</url>
  </required_header>
  <id_info>
    <org_study_id>CCR 5165</org_study_id>
    <nct_id>NCT04407676</nct_id>
  </id_info>
  <brief_title>Improving Informed Consent for Early Phase Anti-Cancer Trials</brief_title>
  <acronym>CONSENT</acronym>
  <official_title>A Randomised Controlled Trial of Enhanced Informed Consent Compared to Standard Informed Consent To Improve Patient Understanding of Early Phase Oncology Clinical Trials</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Royal Marsden NHS Foundation Trust</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Royal Marsden NHS Foundation Trust</source>
  <oversight_info>
    <has_dmc>No</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 purpose of the trial will be to test whether providing both a short summary PIS and a&#xD;
      link to a set of online video modules will improve patient understanding (those considering&#xD;
      early phase clinical trials) as measured on the Quality of Informed Consent questionnaire&#xD;
      (Part A), as compared to a control group who are provided only the normal PIS, and also to&#xD;
      assess user acceptability and feasibility of these interventions.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      i. General background&#xD;
&#xD;
      Early phase oncology clinical trials are becoming increasingly complex with a rapidly&#xD;
      increasing array of investigational agents, combinations of these agents and a variety of&#xD;
      trial designs which incorporate the importance of personalised approaches and the hope of&#xD;
      fast tracked drug discovery. Informed consent for early phase oncology trials has always been&#xD;
      a contentious area, and now it continues to be of relevance for the wider oncology community&#xD;
      and the Phase 1 trial community. A 2018 study demonstrated significant gaps in understanding&#xD;
      of patients regarding the nature and intent of early phase oncology trials. There has been a&#xD;
      longstanding debate in the medical oncology community about the nature of Phase 1 trials and&#xD;
      the ethics of allowing vulnerable patients to participate in clinical research where the&#xD;
      primary purpose is to establish the safe dose. Opponents of the argument point to the need to&#xD;
      understand both sides and that patients need to understand enough to consent, which is not&#xD;
      necessarily full comprehension. The fact that this group of patients is hopeful, optimistic&#xD;
      and desperate has been well characterized and no doubt plays a role in their ability to&#xD;
      process information presented to them by the clinical research team.&#xD;
&#xD;
      ii. Empirical research showing patients misunderstand early phase clinical trials&#xD;
&#xD;
      Multiple studies have shown that advanced cancer patients (ACP) misunderstand the nature and&#xD;
      purpose of Phase 1 oncology trials. Most recently, Hlubocky et al. demonstrated through&#xD;
      audiotaping clinical encounters between 101 ACPs, and 29 oncologists that ACPs had a poor&#xD;
      understanding. Only 26% were able to recall the primary purpose of the trial as safety and&#xD;
      only 7% were able to recall that there was a risk of major adverse effects such as organ&#xD;
      damage. The study also demonstrated deficiencies in clinician communication, with only 40% of&#xD;
      encounters containing a direct statement on the research purpose being to establish safety,&#xD;
      toxicity and dosage. In 2010, a similar study of 17 oncologists and 52 patients in the United&#xD;
      Kingdom showed that several key areas of information including prognosis were omitted from&#xD;
      the clinical encounter.Joffe and colleagues also conducted a survey of trial participants&#xD;
      (including phase 1, 2 and 3 clinical trials) and investigators and showed significant&#xD;
      deficits in understanding. Furthermore, in a survey of 95 patients on Phase 1 trials, Pentz&#xD;
      and colleagues demonstrated that 68.4% of patients had a therapeutic misconception by failing&#xD;
      to answer two core questions correctly (&quot;Is the research study mostly intending to help&#xD;
      research and gain knowledge or mostly intending to help you as a person?&quot; and &quot;Does the&#xD;
      research study or your doctor decide the treatments?&quot;). There was also a misunderstanding of&#xD;
      the risk associated with participating in an early phase clinical trial and that they do not&#xD;
      correctly grasp the key difference between individualized care and clinical research. There&#xD;
      was a correlation between lower education and lower family incomes with therapeutic&#xD;
      misconception. Overall there is extensive empirical evidence to suggest that a significant&#xD;
      proportion of advanced cancer patients considering early phase oncology clinical trials&#xD;
      harbour misconceptions about the nature and design of these trials.&#xD;
&#xD;
      iii. Participant Information Sheets are too long, too complex and fail to meet the&#xD;
      information needs of patients&#xD;
&#xD;
      It has long been recognised that Participant Information Sheets (PIS) or Informed Consent&#xD;
      Forms (ICF) are highly complex and lengthy across all the phases of oncology clinical trials.&#xD;
      In 2007, Beardsley and colleagues showed that PIS were increasing in length and that an&#xD;
      objective measure of informed consent (the QuIC-A), understanding decreased as PIS's&#xD;
      increased in length. There have been no published studies on the PIS used in Phase 1 studies&#xD;
      specifically. However, in the era of combination trials, Bayesian adaptive design, and&#xD;
      seamless Phase 1/2 designs, the PIS for Phase 1 trials can be particularly complex. There is&#xD;
      regulatory requirement for disclosure and there are certain regulatory requirements but these&#xD;
      documents have ultimately become unwieldy, disliked by investigators and anecdotally, not&#xD;
      read at all by participants. This further magnifies the issues on therapeutic misconception&#xD;
      that were highlighted earlier. We note that the Hastings Center has published a 3 page Phase&#xD;
      1 consent form, but to the best of our knowledge this is not in widespread practice. Overall,&#xD;
      in this era of increasingly sophisticated trial design, PIS are becoming lengthier and are&#xD;
      becoming less useful as adjuncts to the informed consent process.&#xD;
&#xD;
      iv. Paucity of interventional research to improve understanding&#xD;
&#xD;
      We performed a review of the literature looking at interventions that have been tested to&#xD;
      improve participant comprehension of Phase 1 trials which yielded two relevant studies. The&#xD;
      first, a simulated teaching intervention to improve clinician confidence by Fallowfield et&#xD;
      al. (2012) showed that an intensive 8 hour educational intervention on clinicians involved in&#xD;
      early phase trials improved their self-confidence along with patient simulator ratings of&#xD;
      understanding(7). Secondly, Kass et al. (2009) randomized 288 participants to receive either&#xD;
      a 20 minute educational computer based presentation or a standard pamphlet on clinical trials&#xD;
      and showed that they could improve patient understanding of trial purpose from 16% to 34%(8)&#xD;
      and also showed that there was no significant differences in likelihood of enrollment. We&#xD;
      note that there have been multiple efforts directed towards empowering cancer patients in&#xD;
      later phase trials including audiovisual techniques such as multimedia presentations(9),&#xD;
      question prompt lists(10), and decision aids (11). Promisingly, sponsors are already taking&#xD;
      steps towards improving their information sheets and there are already attempts to&#xD;
      incorporate audiovisual materials and electronic assessment of patient understanding.&#xD;
&#xD;
      v. Justification for CONSENT&#xD;
&#xD;
      CONSENT will be a randomised controlled trial examining the effect of both a short,&#xD;
      jargon-free, plain language participant information sheet and a suite of online educational&#xD;
      videos, on participants considering consenting to an investigator initiated trial within the&#xD;
      Drug Development Unit. Early phase trials have dramatically changed over the last decade and&#xD;
      there have been no interventional studies published in this area in this time and&#xD;
      consequently this is a significant area of unmet need for both patients and investigators.&#xD;
      This trial will use a validated measure of informed consent (Quality of Informed Consent -&#xD;
      Part A) and powered to test a statistical hypothesis, and will also examine the acceptability&#xD;
      of the two interventions for patients. While the trial will employ a randomised design, it&#xD;
      will ensure all participants are provided access to the enhanced consent materials prior to&#xD;
      their actual consent visit to ensure fairness. This trial will be conducted in compliance&#xD;
      with the protocol, standard operating procedures, policies, local R&amp;D management guidance,&#xD;
      Good Clinical Practice including the UK Policy Framework for Health and Social Care.&#xD;
&#xD;
      Research Governance Framework 2005 (2nd edition)&#xD;
&#xD;
      2. Rationale&#xD;
&#xD;
      Given the ethical imperative to ensure patients understand the nature and conduct of clinical&#xD;
      trials, the clearly documented lack of understanding in the literature, we propose this trial&#xD;
      to examine whether a pragmatic and deliverable program of &quot;enhanced&quot; informed consent can&#xD;
      impact upon patient objective and subjective understanding. The first part of this enhanced&#xD;
      consent will be a summary PIS (example attached in appendix) which contains the absolutely&#xD;
      necessary information for patients - we have already conducted a qualitative study of patient&#xD;
      focus groups and have asked patients directly their priorities. The top three priorities&#xD;
      identified patients were&#xD;
&#xD;
        1. Will this trial work for me?&#xD;
&#xD;
        2. What are the side effects?&#xD;
&#xD;
        3. How often do I have to come? This will consist of an easy to understand flowchart.&#xD;
&#xD;
      The second part of this enhanced consent will be an online link to 10 video modules&#xD;
      (transcripts attached in appendix) covering key areas of the consent. During the development&#xD;
      process of these educational tools, we performed a qualitative analysis of transcripts of&#xD;
      interviews of consultants, study managers, clinical fellows, clinical research nurses and&#xD;
      patients of the DDU and identified the key areas that the various stakeholders wished to&#xD;
      communicate to patients. We asked about the key areas that need to be communicated, common&#xD;
      areas of misunderstanding and preferred ways forward of improving patient understanding.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">June 26, 2020</start_date>
  <completion_date type="Anticipated">March 26, 2023</completion_date>
  <primary_completion_date type="Anticipated">November 26, 2022</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Crossover Assignment</intervention_model>
    <intervention_model_description>Randomised</intervention_model_description>
    <primary_purpose>Supportive Care</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>QuIC-A score (Quality of Informed Consent questionnaire - Part A, Objective)</measure>
    <time_frame>Through study completion, aiming for 34 patients, expected to reach this in 12 months based on historical recruitment rates</time_frame>
    <description>• To determine the QuIC Part A scores following administration of a standard PIS alone, and compare it to the QuIC Part A score following administration of a standard PIS along with a summary PIS and a suite of online educational videos. Minimum score on QuIC-A is 0, highest is 100, and higher scores indicate a higher degree of objective understanding of clinical trial principles.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>QuIC- B score (Quality of Informed Consent questionnaire - Part B, Subjective)</measure>
    <time_frame>Through study completion, aiming for 34 patients, expected to reach this in 12 months based on historical recruitment rates</time_frame>
    <description>• To determine the QuIC Part B scores following administration of a normal PIS alone, and compare it to the QuIC Part B score following administration of a normal PIS along with a summary PIS and a suite of online educational videos. Minimum score on QuIC-B is 0, highest is 100, and higher scores indicate a higher degree of subjective understanding of clinical trial principles.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Control arm analysis</measure>
    <time_frame>Through study completion, aiming for 34 patients, expected to reach this in 12 months based on historical recruitment rates</time_frame>
    <description>• To determine the changes in QuIC Part A and Part B scores before and after administration of enhanced consent materials</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>User feedback</measure>
    <time_frame>Through study completion, aiming for 34 patients, expected to reach this in 12 months based on historical recruitment rates</time_frame>
    <description>• To confirm the acceptability and utility of the summary PIS and educational videos with a user feedback survey</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>GBM cohort exploratory analysis</measure>
    <time_frame>Through study completion, aiming for 15 patients, expected to reach this in 12 months based on historical recruitment rates</time_frame>
    <description>QuIC Part A and Part B scores before and after administration of enhanced consent materials in patients recruited to the GBM cohort in the ICE-CAP study</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">34</enrollment>
  <condition>Solid Neoplasms</condition>
  <arm_group>
    <arm_group_label>Experimental</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients eligible for an investigator initiated trial are given the standard PIS by email, and are also emailed a summary PIS and access to an online set of 10 video educational modules. They are then administered a demographic data collection form, the Quality of Informed Consent Questionnaire Parts A and B, and a user feedback survey form. They then present for their standard of care consent visit.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Control</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Patients eligible for an investigator initiated trial are given the standard PIS by email and are then administered a demographic data collection form, the Quality of Informed Consent Questionnaire Parts A and B, and a user feedback survey form. They will then be emailed and are also emailed a summary PIS and access to an online set of 10 video educational modules. They will then perform the QuIC-A and QuIC-B again. They will then present for their standard of care consent visit.</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Summary PIS and Online Video Modules</intervention_name>
    <description>Complex trial information presented in alternative and more accessible formats</description>
    <arm_group_label>Control</arm_group_label>
    <arm_group_label>Experimental</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion criteria&#xD;
&#xD;
          1. For randomised participation, patients must be eligible for an Investigator Initiated&#xD;
             Trial (IIT) within the Drug Development Unit&#xD;
&#xD;
               1. RAFMEK (IRAS 102403, CCR 3808, REC ref: 12/LO/1407)&#xD;
&#xD;
               2. FRAME (IRAS 225064, CCR 4642, REC ref: 17/LO/1473)&#xD;
&#xD;
               3. ICE-CAP (IRAS 233461, CCR 4720, REC ref: 18/LO/0059), non GBM cohorts&#xD;
&#xD;
               4. ACE (IRAS Number 211557, CCR 4500, REC ref: 17/LO/0263)&#xD;
&#xD;
               5. Other IIT trials as they open, however these trials and accompanying study aids&#xD;
                  will be added as an amendment to CONSENT&#xD;
&#xD;
             For participation in non-randomised secondary analysis of GBM patients, patients must&#xD;
             be eligible for&#xD;
&#xD;
             a. ICE-CAP (IRAS 233461, CCR 4720, REC ref: 18/LO/0059), GBM cohorts&#xD;
&#xD;
          2. English is the patient's primary language&#xD;
&#xD;
          3. Written (signed and dated) informed consent and be capable of co-operating with study&#xD;
             procedures and questionnaire&#xD;
&#xD;
        Exclusion criteria&#xD;
&#xD;
          1. Pre-existing visual, non-cancer related cognitive impairment, or reading impairment&#xD;
&#xD;
          2. Patients who have already consented to a trial or have prior consent knowledge&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Juanita Lopez, MRCP PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>The Royal Marsden Hospital NHS Foundation Trust</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Juanita Lopez, MRCP PhD</last_name>
    <phone>+44 8642 6011</phone>
    <email>juanita.lopez@icr.ac.uk</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Abhijit Pal, MBBS FRACP</last_name>
    <phone>+44 8642 6011</phone>
    <email>abhijit.pal@icr.ac.uk</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Royal Marsden Hospital NHS Foundation Trust</name>
      <address>
        <city>London</city>
        <zip>SW3 6JJ</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Ann Gandolfi</last_name>
      <phone>02086613903</phone>
      <email>ann.gandolfi@rmh.nhs.uk</email>
    </contact>
  </location>
  <location_countries>
    <country>United Kingdom</country>
  </location_countries>
  <reference>
    <citation>Hlubocky FJ, Kass NE, Roter D, Larson S, Wroblewski KE, Sugarman J, Daugherty CK. Investigator Disclosure and Advanced Cancer Patient Understanding of Informed Consent and Prognosis in Phase I Clinical Trials. J Oncol Pract. 2018 Jun;14(6):e357-e367. doi: 10.1200/JOP.18.00028. Epub 2018 May 22. Erratum In: J Oncol Pract. 2018 Jul;14(7):452.</citation>
    <PMID>29787333</PMID>
  </reference>
  <reference>
    <citation>Miller FG, Joffe S. Phase 1 oncology trials and informed consent. J Med Ethics. 2013 Dec;39(12):761-4. doi: 10.1136/medethics-2012-100832. Epub 2012 Nov 17.</citation>
    <PMID>23161617</PMID>
  </reference>
  <reference>
    <citation>Dolly SO, Kalaitzaki E, Puglisi M, Stimpson S, Hanwell J, Fandos SS, Stapleton S, Ansari T, Peckitt C, Kaye S, Lopez J, Yap TA, van der Graaf W, de Bono J, Banerji U. A study of motivations and expectations of patients seen in phase 1 oncology clinics. Cancer. 2016 Nov 15;122(22):3501-3508. doi: 10.1002/cncr.30235. Epub 2016 Sep 26.</citation>
    <PMID>27716902</PMID>
  </reference>
  <reference>
    <citation>Jenkins V, Solis-Trapala I, Langridge C, Catt S, Talbot DC, Fallowfield LJ. What oncologists believe they said and what patients believe they heard: an analysis of phase I trial discussions. J Clin Oncol. 2011 Jan 1;29(1):61-8. doi: 10.1200/JCO.2010.30.0814. Epub 2010 Nov 22.</citation>
    <PMID>21098322</PMID>
  </reference>
  <reference>
    <citation>Joffe S, Cook EF, Cleary PD, Clark JW, Weeks JC. Quality of informed consent in cancer clinical trials: a cross-sectional survey. Lancet. 2001 Nov 24;358(9295):1772-7. doi: 10.1016/S0140-6736(01)06805-2.</citation>
    <PMID>11734235</PMID>
  </reference>
  <reference>
    <citation>Koyfman SA, McCabe MS, Emanuel EJ, Grady C. A consent form template for phase I oncology trials. IRB. 2009 Jul-Aug;31(4):1-8. No abstract available.</citation>
    <PMID>19697538</PMID>
  </reference>
  <reference>
    <citation>Fallowfield LJ, Solis-Trapala I, Jenkins VA. Evaluation of an educational program to improve communication with patients about early-phase trial participation. Oncologist. 2012;17(3):377-83. doi: 10.1634/theoncologist.2011-0271. Epub 2012 Mar 1.</citation>
    <PMID>22382459</PMID>
  </reference>
  <reference>
    <citation>Kass NE, Sugarman J, Medley AM, Fogarty LA, Taylor HA, Daugherty CK, Emerson MR, Goodman SN, Hlubocky FJ, Hurwitz HI, Carducci M, Goodwin-Landher A. An intervention to improve cancer patients' understanding of early-phase clinical trials. IRB. 2009 May-Jun;31(3):1-10. No abstract available.</citation>
    <PMID>19552233</PMID>
  </reference>
  <reference>
    <citation>Synnot A, Ryan R, Prictor M, Fetherstonhaugh D, Parker B. Audio-visual presentation of information for informed consent for participation in clinical trials. Cochrane Database Syst Rev. 2014 May 9;2014(5):CD003717. doi: 10.1002/14651858.CD003717.pub3.</citation>
    <PMID>24809816</PMID>
  </reference>
  <reference>
    <citation>Tattersall MH, Jefford M, Martin A, Olver I, Thompson JF, Brown RF, Butow PN. Parallel multicentre randomised trial of a clinical trial question prompt list in patients considering participation in phase 3 cancer treatment trials. BMJ Open. 2017 Mar 1;7(3):e012666. doi: 10.1136/bmjopen-2016-012666.</citation>
    <PMID>28249847</PMID>
  </reference>
  <reference>
    <citation>Juraskova I, Butow P, Bonner C, Bell ML, Smith AB, Seccombe M, Boyle F, Reaby L, Cuzick J, Forbes JF. Improving decision making about clinical trial participation - a randomised controlled trial of a decision aid for women considering participation in the IBIS-II breast cancer prevention trial. Br J Cancer. 2014 Jul 8;111(1):1-7. doi: 10.1038/bjc.2014.144. Epub 2014 Jun 3.</citation>
    <PMID>24892447</PMID>
  </reference>
  <reference>
    <citation>Joffe S, Cook EF, Cleary PD, Clark JW, Weeks JC. Quality of informed consent: a new measure of understanding among research subjects. J Natl Cancer Inst. 2001 Jan 17;93(2):139-47. doi: 10.1093/jnci/93.2.139.</citation>
    <PMID>11208884</PMID>
  </reference>
  <reference>
    <citation>Hoffner B, Bauer-Wu S, Hitchcock-Bryan S, Powell M, Wolanski A, Joffe S. &quot;Entering a Clinical Trial: Is it Right for You?&quot;: a randomized study of The Clinical Trials Video and its impact on the informed consent process. Cancer. 2012 Apr 1;118(7):1877-83. doi: 10.1002/cncr.26438. Epub 2011 Aug 25.</citation>
    <PMID>22009665</PMID>
  </reference>
  <reference>
    <citation>Spellecy R, Tarima S, Denzen E, Moore H, Abhyankar S, Dawson P, Foley A, Gersten I, Horwitz M, Idossa L, Joffe S, Kamani N, King R, Lazaryan A, Morris L, Horowitz MM, Majhail NS. Easy-to-Read Informed Consent Form for Hematopoietic Cell Transplantation Clinical Trials: Results from the Blood and Marrow Transplant Clinical Trials Network 1205 Study. Biol Blood Marrow Transplant. 2018 Oct;24(10):2145-2151. doi: 10.1016/j.bbmt.2018.04.014. Epub 2018 Apr 18.</citation>
    <PMID>29679770</PMID>
  </reference>
  <verification_date>February 2022</verification_date>
  <study_first_submitted>May 21, 2020</study_first_submitted>
  <study_first_submitted_qc>May 28, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">May 29, 2020</study_first_posted>
  <last_update_submitted>February 17, 2022</last_update_submitted>
  <last_update_submitted_qc>February 17, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">March 4, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Drug Development</keyword>
  <keyword>Informed consent</keyword>
  <keyword>Clinical Trials</keyword>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- 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/NCT04407676
org study id: CCR 5165
nct id: NCT04407676
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
The purpose of the trial will be to test whether providing both a short summary PIS and a
      link to a set of online video modules will improve patient understanding (those considering
      early phase clinical trials) as measured on the Quality of Informed Consent questionnaire
      (Part A), as compared to a control group who are provided only the normal PIS, and also to
      assess user acceptability and feasibility of these interventions.
i. General background

      Early phase oncology clinical trials are becoming increasingly complex with a rapidly
      increasing array of investigational agents, combinations of these agents and a variety of
      trial designs which incorporate the importance of personalised approaches and the hope of
      fast tracked drug discovery. Informed consent for early phase oncology trials has always been
      a contentious area, and now it continues to be of relevance for the wider oncology community
      and the Phase 1 trial community. A 2018 study demonstrated significant gaps in understanding
      of patients regarding the nature and intent of early phase oncology trials. There has been a
      longstanding debate in the medical oncology community about the nature of Phase 1 trials and
      the ethics of allowing vulnerable patients to participate in clinical research where the
      primary purpose is to establish the safe dose. Opponents of the argument point to the need to
      understand both sides and that patients need to understand enough to consent, which is not
      necessarily full comprehension. The fact that this group of patients is hopeful, optimistic
      and desperate has been well characterized and no doubt plays a role in their ability to
      process information presented to them by the clinical research team.

      ii. Empirical research showing patients misunderstand early phase clinical trials

      Multiple studies have shown that advanced cancer patients (ACP) misunderstand the nature and
      purpose of Phase 1 oncology trials. Most recently, Hlubocky et al. demonstrated through
      audiotaping clinical encounters between 101 ACPs, and 29 oncologists that ACPs had a poor
      understanding. Only 26% were able to recall the primary purpose of the trial as safety and
      only 7% were able to recall that there was a risk of major adverse effects such as organ
      damage. The study also demonstrated deficiencies in clinician communication, with only 40% of
      encounters containing a direct statement on the research purpose being to establish safety,
      toxicity and dosage. In 2010, a similar study of 17 oncologists and 52 patients in the United
      Kingdom showed that several key areas of information including prognosis were omitted from
      the clinical encounter.Joffe and colleagues also conducted a survey of trial participants
      (including phase 1, 2 and 3 clinical trials) and investigators and showed significant
      deficits in understanding. Furthermore, in a survey of 95 patients on Phase 1 trials, Pentz
      and colleagues demonstrated that 68.4% of patients had a therapeutic misconception by failing
      to answer two core questions correctly ("Is the research study mostly intending to help
      research and gain knowledge or mostly intending to help you as a person?" and "Does the
      research study or your doctor decide the treatments?"). There was also a misunderstanding of
      the risk associated with participating in an early phase clinical trial and that they do not
      correctly grasp the key difference between individualized care and clinical research. There
      was a correlation between lower education and lower family incomes with therapeutic
      misconception. Overall there is extensive empirical evidence to suggest that a significant
      proportion of advanced cancer patients considering early phase oncology clinical trials
      harbour misconceptions about the nature and design of these trials.

      iii. Participant Information Sheets are too long, too complex and fail to meet the
      information needs of patients

      It has long been recognised that Participant Information Sheets (PIS) or Informed Consent
      Forms (ICF) are highly complex and lengthy across all the phases of oncology clinical trials.
      In 2007, Beardsley and colleagues showed that PIS were increasing in length and that an
      objective measure of informed consent (the QuIC-A), understanding decreased as PIS's
      increased in length. There have been no published studies on the PIS used in Phase 1 studies
      specifically. However, in the era of combination trials, Bayesian adaptive design, and
      seamless Phase 1/2 designs, the PIS for Phase 1 trials can be particularly complex. There is
      regulatory requirement for disclosure and there are certain regulatory requirements but these
      documents have ultimately become unwieldy, disliked by investigators and anecdotally, not
      read at all by participants. This further magnifies the issues on therapeutic misconception
      that were highlighted earlier. We note that the Hastings Center has published a 3 page Phase
      1 consent form, but to the best of our knowledge this is not in widespread practice. Overall,
      in this era of increasingly sophisticated trial design, PIS are becoming lengthier and are
      becoming less useful as adjuncts to the informed consent process.

      iv. Paucity of interventional research to improve understanding

      We performed a review of the literature looking at interventions that have been tested to
      improve participant comprehension of Phase 1 trials which yielded two relevant studies. The
      first, a simulated teaching intervention to improve clinician confidence by Fallowfield et
      al. (2012) showed that an intensive 8 hour educational intervention on clinicians involved in
      early phase trials improved their self-confidence along with patient simulator ratings of
      understanding(7). Secondly, Kass et al. (2009) randomized 288 participants to receive either
      a 20 minute educational computer based presentation or a standard pamphlet on clinical trials
      and showed that they could improve patient understanding of trial purpose from 16% to 34%(8)
      and also showed that there was no significant differences in likelihood of enrollment. We
      note that there have been multiple efforts directed towards empowering cancer patients in
      later phase trials including audiovisual techniques such as multimedia presentations(9),
      question prompt lists(10), and decision aids (11). Promisingly, sponsors are already taking
      steps towards improving their information sheets and there are already attempts to
      incorporate audiovisual materials and electronic assessment of patient understanding.

      v. Justification for CONSENT

      CONSENT will be a randomised controlled trial examining the effect of both a short,
      jargon-free, plain language participant information sheet and a suite of online educational
      videos, on participants considering consenting to an investigator initiated trial within the
      Drug Development Unit. Early phase trials have dramatically changed over the last decade and
      there have been no interventional studies published in this area in this time and
      consequently this is a significant area of unmet need for both patients and investigators.
      This trial will use a validated measure of informed consent (Quality of Informed Consent -
      Part A) and powered to test a statistical hypothesis, and will also examine the acceptability
      of the two interventions for patients. While the trial will employ a randomised design, it
      will ensure all participants are provided access to the enhanced consent materials prior to
      their actual consent visit to ensure fairness. This trial will be conducted in compliance
      with the protocol, standard operating procedures, policies, local R&D management guidance,
      Good Clinical Practice including the UK Policy Framework for Health and Social Care.

      Research Governance Framework 2005 (2nd edition)

      2. Rationale

      Given the ethical imperative to ensure patients understand the nature and conduct of clinical
      trials, the clearly documented lack of understanding in the literature, we propose this trial
      to examine whether a pragmatic and deliverable program of "enhanced" informed consent can
      impact upon patient objective and subjective understanding. The first part of this enhanced
      consent will be a summary PIS (example attached in appendix) which contains the absolutely
      necessary information for patients - we have already conducted a qualitative study of patient
      focus groups and have asked patients directly their priorities. The top three priorities
      identified patients were

        1. Will this trial work for me?

        2. What are the side effects?

        3. How often do I have to come? This will consist of an easy to understand flowchart.

      The second part of this enhanced consent will be an online link to 10 video modules
      (transcripts attached in appendix) covering key areas of the consent. During the development
      process of these educational tools, we performed a qualitative analysis of transcripts of
      interviews of consultants, study managers, clinical fellows, clinical research nurses and
      patients of the DDU and identified the key areas that the various stakeholders wished to
      communicate to patients. We asked about the key areas that need to be communicated, common
      areas of misunderstanding and preferred ways forward of improving patient understanding.
allocation: Randomized
intervention model: Crossover Assignment
intervention model description: Randomised
primary purpose: Supportive Care
masking: None (Open Label)
measure: QuIC-A score (Quality of Informed Consent questionnaire - Part A, Objective)
time frame: Through study completion, aiming for 34 patients, expected to reach this in 12 months based on historical recruitment rates
description: • To determine the QuIC Part A scores following administration of a standard PIS alone, and compare it to the QuIC Part A score following administration of a standard PIS along with a summary PIS and a suite of online educational videos. Minimum score on QuIC-A is 0, highest is 100, and higher scores indicate a higher degree of objective understanding of clinical trial principles.
measure: QuIC- B score (Quality of Informed Consent questionnaire - Part B, Subjective)
time frame: Through study completion, aiming for 34 patients, expected to reach this in 12 months based on historical recruitment rates
description: • To determine the QuIC Part B scores following administration of a normal PIS alone, and compare it to the QuIC Part B score following administration of a normal PIS along with a summary PIS and a suite of online educational videos. Minimum score on QuIC-B is 0, highest is 100, and higher scores indicate a higher degree of subjective understanding of clinical trial principles.
measure: Control arm analysis
time frame: Through study completion, aiming for 34 patients, expected to reach this in 12 months based on historical recruitment rates
description: • To determine the changes in QuIC Part A and Part B scores before and after administration of enhanced consent materials
measure: User feedback
time frame: Through study completion, aiming for 34 patients, expected to reach this in 12 months based on historical recruitment rates
description: • To confirm the acceptability and utility of the summary PIS and educational videos with a user feedback survey
measure: GBM cohort exploratory analysis
time frame: Through study completion, aiming for 15 patients, expected to reach this in 12 months based on historical recruitment rates
description: QuIC Part A and Part B scores before and after administration of enhanced consent materials in patients recruited to the GBM cohort in the ICE-CAP study
arm group label: Experimental
arm group type: Experimental
description: Patients eligible for an investigator initiated trial are given the standard PIS by email, and are also emailed a summary PIS and access to an online set of 10 video educational modules. They are then administered a demographic data collection form, the Quality of Informed Consent Questionnaire Parts A and B, and a user feedback survey form. They then present for their standard of care consent visit.
arm group label: Control
arm group type: Placebo Comparator
description: Patients eligible for an investigator initiated trial are given the standard PIS by email and are then administered a demographic data collection form, the Quality of Informed Consent Questionnaire Parts A and B, and a user feedback survey form. They will then be emailed and are also emailed a summary PIS and access to an online set of 10 video educational modules. They will then perform the QuIC-A and QuIC-B again. They will then present for their standard of care consent visit.
intervention type: Other
intervention name: Summary PIS and Online Video Modules
description: Complex trial information presented in alternative and more accessible formats
arm group label: Control
arm group label: Experimental
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Juanita Lopez, MRCP PhD
role: Principal Investigator
affiliation: The Royal Marsden Hospital NHS Foundation Trust
last name: Juanita Lopez, MRCP PhD
phone: +44 8642 6011
email: juanita.lopez@icr.ac.uk
last name: Abhijit Pal, MBBS FRACP
phone: +44 8642 6011
email: abhijit.pal@icr.ac.uk
facility: 
status: Recruiting
contact: 
country: United Kingdom
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PMID: 29787333
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PMID: 21098322
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PMID: 11734235
citation: Koyfman SA, McCabe MS, Emanuel EJ, Grady C. A consent form template for phase I oncology trials. IRB. 2009 Jul-Aug;31(4):1-8. No abstract available.
PMID: 19697538
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PMID: 19552233
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PMID: 24809816
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PMID: 28249847
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PMID: 29679770
responsible party type: Sponsor
sharing ipd: No