Dr. R. S. Sharma is Deputy Director of Reproductive Health and Nutrition at the Indian Council of Medical Research, the government agency which plans and guides medical studies. He's a busy man, with oversight over, among other things, both male contraceptive research and national in vitro fertilization standards. We caught up with him this month for an update on RISUG, the multi-year, non-hormonal vas deferens-based injectable male contraceptive currently in the last stage of studies on men in India. His responses have been edited to simplify technical language.
Male Contraception Information Project: How is the RISUG clinical trial proceeding?
Dr. R.S. Sharma: We are currently running two studies: one a follow-up study and the other a Phase III clinical trial In the follow-up study, we are following all the subjects, and so far have tested about 66. For comparison, we have also identified and followed about 44 No Scalpel Vasectomy (NSV) subjects and given them health and sperm count exams. No health problems have been noticed in any of the subjects in either group by 5 to 7 years after RISUG injection. There have been no intact sperm in any of the follow-up subjects even after 5 to 7 years.
In the new Phase III trial, we have started the study at four centers around the country, and have injected RISUG in about 64 subjects; the goal will be to enroll a total of 500 subjects. It is a slow process to get these studies started, and we had to complete many steps: we've done a workshop to train the paramedical staff, a workshop to train the investigators in injection procedures, and more.
I recently got the 6-month report on this study, at which time 64 injection procedures had been performed. The data received is under analysis, but it appears that there were no intact sperm in any of the 64 subjects.
MCIP: No intact sperm – no whole, undamaged sperm able to swim – in any of the 64 subjects in the new study?
Sharma: Yes, that is correct. Although the detailed analysis is still going on, we are also quite encouraged that we have not come across any major side effects. This time, of the type of the swelling and pain noted occasionally in the last trial, the pain was not there, and the swelling was much less and went away quicly, within a week in both cases. I think the professionally manufactured drug may be helping - the drug was manufactured by a pharmaceutical company rather than in the laboratory, and that may be making a difference. But also, it may be due to training: we have designated a master trainer who is training all the new investigators in the injection procedure under the supervision of experts and also supervising the investigators in the beginning stages until they have perfected it.
MCIP: Those are incredible results! When might we see publication of this data? People are very excited about the possibility of a long-acting male contraceptive, but so far all the claims of long-term efficacy and reversibility have been based on animal data plus informal news from the men who stayed in touch. Why not publish data on the men from the one study site while you track down the others?
Sharma: Sixty six subjects is good, and this is certainly encouraging information, but we will feel more confident about having significant data if we can report on at least 100 of the 139 subjects. I have thought about publishing the interim results of the one study, but we have been stretched thin. There is another factor: we are following the NSV [No-Scalpel Vasectomy] group from the same time and the same duration of use, and we are focused on publishing the full comparison of the data sets. The results of the comparison between the two will be very important.
MCIP: What about reversibility? This is another issue where we've had to extrapolate from monkey studies. Reversibility is the key to opening up RISUG use to a whole generation of men not ready for permanent vasectomy. But there's always that nagging issue in the back of our minds: sure, monkeys can use it for a year and a half and still regain fertility upon reversal, and sure, publications show men's prostate markers and reproductive organs are normal even after years of use; but does that mean a man could really father a child after 5 or 10 years of use?
Sharma: Yes, reversibility is the issue. It's very, very important for us to look at this.
We are planning a study to do reversal in a few subjects from the Phase I trial [17 or more years of use], Phase II trial [about 12 years of use], and/or Limited Phase III trial [6-7 years of use]. Even after designing a study of reversibility, it will still be quite challenging: It's not in our hands to know how many men will accept reversal. We'll try our best to get enough, though. This is certainly a very important issue we need to address.
MCIP: What are the next steps in this research?
Sharma: One of the most important steps is conducting a reversibility study, and extending the ongoing Phase III trial to 6 more centers.
MCIP: What do you see as a major hurdle or concern for RISUG?
Sharma: The enrollment of the subjects in the Phase III clinical trial is very poor. In India, male participation is poor even for vasectomy or NSV compared to female sterilization. So our main issue is to attract the male to accept this contraception option. It takes time to convince people, but we're taking steps such as placing ads in the newspaper and holding information meetings.
MCIP: But we were under the impression that there is a waitlist for injections, and the obstacle is steady supply of the RISUG material?
Sharma: That was an issue before, but it has been solved.
MCIP: Surely the well-educated urban men would be among the first adopters of this new technology, and publicity in the press would result in a great demand? Is there any role for publicity?
Sharma: Perhaps there could be a role for a joint effort in this area. I have been contacted by quite a few men from outside India who want to get RISUG, but the government hasn't permitted foreigners to participate in the trial, so we have to turn them down.
MCIP: Is there any other male contraceptive research you are excited about or would like to comment on?
Sharma: I am currently concentrating on RISUG, but I am also interested in promoting data-driven condom development. At the government's request, I was the first person to collect specifications [for appropriate size and shape] for condoms, and I found state-to-state variation within the country of India. If we want condoms to be effective and accepted, then we need to develop condoms to the correct specifications.
If my plate weren't so full, I would like to be collecting data for the regions that we didn't study, and testing the efficacy and acceptability of new condoms developed based on these new specifications. Condoms are extremely important, with a dual purpose as both a contraceptive and preventing the spread of HIV and other STDs.
MCIP: Thank you so much for your time, Dr. Sharma!