AccuReg: Soliciting for Clinical Study Participants

The Regulatory Clinic - January 1998
Soliciting for Clinical Study Participants

Dear Clinic:

As an independent clinical auditor, I came across a misfiled letter to a primary care physician, notifying the doctor that one of her patients was enrolled in a study at a site that only does clinical trials, Phases I-IV.

The letter ended by inquiring whether the physician was aware of any other patients in her practice whom she could refer to the trial. The paragraphs gave only the indication of the trial and drug. The writer offered $200 for any patient who could be enrolled (randomized) and for whom the primary care physician would send a completed diagnostic assessment.

My concerns are that this is recruitment or advertising that was not approved by the IRB, that the primary care physician is unaware of the risks and benefits of the trial, that the primary MD is completing and releasing an assessment for a fee without being approved and listed on the 1572 for the trial, and that the IRB and Sponsor are unaware of all these things. How does the FDA currently look on such outside activities referring to recruitment?

I would like the opinion of the Clinic as to whether or not the described recruitment activities are acceptable ethically and under the GCPs. As a separate issue, I would also like your comments on abstinence and male vasectomy as acceptable methods of birth control, per Protocol, for clinical study subjects.

Looking forward to your comments,
A Clinically-Concerned Auditor

Dear Auditor:

Thank you for your thought-provoking inquiry. You raised some interesting questions about clinical recruitment practices - many of which emphasize the importance for clinical sites to maintain open lines of communication with study Sponsors and IRBs.

Regarding your concern about "unapproved" recruitment and advertising, the critical factor to weigh is that the correspondence you discovered was a solicitation from one medical professional to another. (Although your message did not state definitively who originated the letter, we presume it was sent over the signature of the Study Investigator or Coordinator.) As such, it is unlikely to be regarded by FDA in the same way as a public solicitation (e.g., a newspaper ad). Nonetheless, as an auditor, your most "upfront" course of action would be to share the letter with both the Sponsor and the IRB as an FYI for their files.
Because this incident was not a "public" solicitation, the IRB would probably be overstepping their authority if they insisted on a change in phraseology of the letter or on abandonment of this type of solicitation. Nonetheless, the IRB should be made aware that this type of recruitment is going on - and if the IRB has comments, the physician and Study Sponsor should take them under consideration.
With regard to the stipend paid to the primary care physician for performing a complete diagnostic assessment, this generally can go one of two ways:
- If the assessment is to be repeated IN FULL by the Study Investigator, and if the patient was not subjected to any additional procedures or risk by their primary physician outside of normal, routine evaluation, then this approach is generally acceptable.
- However, IF the patient is subjected to unusual, non-routine, or "risk-associated" procedures by the primary care physician in performing the diagnostic assessment, then questions of Informed Consent and other regulatory issues are raised. Furthermore, the Study Investigator may NOT rely upon the results of these tests in any way other than to increase his/her confidence that this patient is "likely" to qualify for Study enrollment. In other words, the Investigator cannot include as part of the study any of the data generated by the primary physician.
With regard to male vasectomy as a method of contraception, this is acceptable in a monogamous relationship. Neither sperm counts nor "affidavits of monogamy" are necessary! However, particular emphasis should be placed on this issue during the Informed Consent lest a patient has ANY doubts about whether she MAY place herself and/or her fetus "at risk" if she becomes pregnant during the study.
With regard to abstinence as an approved method of contraception, it is (in the most literal sense) the BEST means of birth control! As with vasectomy, what is called into question is not the effectiveness of the method, but the veracity of the patient! As such, unless the Study Protocol EXPLICITLY excludes abstinence as an acceptable means of birth control, the PI must rely on his/her clinical judgment as to whether the patient is reliable in this regard.
In any case, the clarity of the Informed Consent document and its comprehension by the potential study subject are especially important in these situations. Patients who indicate that they are relying on vasectomy or abstinence for birth control should be queried to confirm they clearly understand these terms (and in the case of vasectomy, the conditions of monogamy). In addition, the Sponsor should be advised of any decision to include patients who claim abstinence as a method of birth control, since depending on the inherent risks associated with study participation, the Sponsor may wish to amend the protocol to exclude such patients, or to require that additional pregnancy testing be reported throughout the Study, etc.

We hope these clarifications are helpful. And from one consultant to another, kudos on your investigative techniques! Your CRO and client Sponsors should be reassured and pleased to know that they are working with such a thorough auditor.

Loui J. Silvestri, PhD
AccuReg, Inc.

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